Association analysis of the vitamin D receptor gene, the type I collagen gene COL1A1, and the estrogen receptor gene in idiopathic osteoarthritis.

PubMed

Loughlin, J; Sinsheimer, J S; Mustafa, Z; Carr, A J; Clipsham, K; Bloomfield, V A; Chitnavis, J; Bailey, A; Sykes, B; Chapman, K

2000-03-01

Evidence has accumulated supporting a role for genes in the etiology of osteoarthritis (OA). Several candidates have been targeted as potential susceptibility loci including genes that are involved in the regulation of bone density. Genetic association analysis has suggested a role for the vitamin D receptor gene (VDR) and the estrogen receptor gene (ER) in susceptibility. Such findings must be tested in additional independent cohorts. We tested for association of these 2 genes, plus a third gene implicated in bone density, COL1A1, with idiopathic OA. A case-control cohort of 371 affected probands and 369 unaffected spouses was used. Association was tested using 4 intragenic single nucleotide polymorphisms (SNP), one each for the VDR and COL1A1 genes, and 2 for the ER gene. The VDR and ER SNP are the same SNP that have been associated with OA. All 4 SNP affect restriction enzyme sites and were genotyped using polymerase chain reaction and enzyme digestion. Allele and genotype distributions for each SNP were compared between cases and controls and analyzed using Fisher's exact test. There was no evidence of association of the VDR or the ER gene SNP to OA. There was weak evidence of association of the COL1A1 SNP in female cases (p = 0.017), reflected by a difference in the distribution of genotypes at this SNP between female cases and controls (p = 0.027). However, when corrected for multiple testing, these results were not significant. If the VDR, ER, or COL1A1 genes do encode predisposition to OA then the 4 SNP tested are not associated with major susceptibility alleles at these 3 loci.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations.

PubMed

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo'o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette; Simo, Gustave

2017-10-01

Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations

PubMed Central

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo’o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette

2017-01-01

Background Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). Methodology A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Results Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204–0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. Conclusion The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP. PMID:29077717

Association between cobalt allergy and dermatitis caused by leather articles--a questionnaire study.

PubMed

Bregnbak, David; Thyssen, Jacob P; Zachariae, Claus; Menné, Torkil; Johansen, Jeanne D

2015-02-01

Cobalt is a strong skin sensitizer and a prevalent contact allergen. Recent studies have recognized exposure to leather articles as a potential cause of cobalt allergy. To examine the association between contact allergy to cobalt and a history of dermatitis resulting from exposure to leather. A questionnaire case-control study was performed: the case group consisted of 183 dermatitis patients with a positive patch test reaction to cobalt chloride and a negative patch test reaction to potassium dichromate; the control group consisted of 621 dermatitis patients who did not react to either cobalt or chromium in patch testing. Comparisons were made by use of a χ(2) -test, Fisher's exact, and the Mann-Whitney test. Logistic regression analyses were used to test for associations while taking confounding factors into consideration. Leather was observed as the most frequent exposure source causing dermatitis in the case group. Although the case group significantly more often reported non-occupational dermatitis caused by leather exposure (p < 0.001), no association was found between cobalt allergy and dermatitis caused by work-related exposure to leather. Our study suggests a positive association between cobalt allergy and a history of dermatitis caused by non-occupational exposure to leather articles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Utilising family-based designs for detecting rare variant disease associations.

PubMed

Preston, Mark D; Dudbridge, Frank

2014-03-01

Rare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family-based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case-control rare variant tests. However, we show that transmission- (or within-family-) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo-case-control design allows a greater range of statistical tests to be applied to family data. © 2014 The Authors. Annals of Human Genetics published by John Wiley & Sons Ltd/University College London.

Design and analysis of multiple diseases genome-wide association studies without controls.

PubMed

Chen, Zhongxue; Huang, Hanwen; Ng, Hon Keung Tony

2012-11-15

In genome-wide association studies (GWAS), multiple diseases with shared controls is one of the case-control study designs. If data obtained from these studies are appropriately analyzed, this design can have several advantages such as improving statistical power in detecting associations and reducing the time and cost in the data collection process. In this paper, we propose a study design for GWAS which involves multiple diseases but without controls. We also propose corresponding statistical data analysis strategy for GWAS with multiple diseases but no controls. Through a simulation study, we show that the statistical association test with the proposed study design is more powerful than the test with single disease sharing common controls, and it has comparable power to the overall test based on the whole dataset including the controls. We also apply the proposed method to a real GWAS dataset to illustrate the methodologies and the advantages of the proposed design. Some possible limitations of this study design and testing method and their solutions are also discussed. Our findings indicate that the proposed study design and statistical analysis strategy could be more efficient than the usual case-control GWAS as well as those with shared controls. Copyright © 2012 Elsevier B.V. All rights reserved.

BETASEQ: a powerful novel method to control type-I error inflation in partially sequenced data for rare variant association testing.

PubMed

Yan, Song; Li, Yun

2014-02-15

Despite its great capability to detect rare variant associations, next-generation sequencing is still prohibitively expensive when applied to large samples. In case-control studies, it is thus appealing to sequence only a subset of cases to discover variants and genotype the identified variants in controls and the remaining cases under the reasonable assumption that causal variants are usually enriched among cases. However, this approach leads to inflated type-I error if analyzed naively for rare variant association. Several methods have been proposed in recent literature to control type-I error at the cost of either excluding some sequenced cases or correcting the genotypes of discovered rare variants. All of these approaches thus suffer from certain extent of information loss and thus are underpowered. We propose a novel method (BETASEQ), which corrects inflation of type-I error by supplementing pseudo-variants while keeps the original sequence and genotype data intact. Extensive simulations and real data analysis demonstrate that, in most practical situations, BETASEQ leads to higher testing powers than existing approaches with guaranteed (controlled or conservative) type-I error. BETASEQ and associated R files, including documentation, examples, are available at http://www.unc.edu/~yunmli/betaseq

Cumulative exposure to lead and cognition in persons with Parkinson's disease.

PubMed

Weuve, Jennifer; Press, Daniel Z; Grodstein, Francine; Wright, Robert O; Hu, Howard; Weisskopf, Marc G

2013-02-01

Dementia is an important consequence of Parkinson's disease (PD), with few known modifiable risk factors. Cumulative exposure to lead, at levels experienced in the community, may exacerbate PD-related neural dysfunction, resulting in impaired cognition. Among 101 persons with PD ("cases") and, separately, 50 persons without PD ("controls"), we evaluated cumulative lead exposure, gauged by tibia and patella bone lead concentrations, in relation to cognitive function, assessed using a telephone battery developed and validated in a separate sample of PD patients. We also assessed the interaction between lead and case-control status. After multivariable adjustment, higher tibia bone lead concentration among PD cases was associated with worse performance on all of the individual telephone tests. In particular, tibia lead levels corresponded to significantly worse performance on a telephone analog of the Mini-Mental State Examination and tests of working memory and attention. Moreover, higher tibia bone lead concentration was associated with significantly worse global composite score encompassing all the cognitive tests (P = 0.04). The magnitude of association per standard deviation increment in tibia bone lead level was equivalent to the difference in global scores among controls in our study, who were approximately 7 years apart in age. The tibia lead-cognition association was notably stronger within cases than within controls (P(difference) = 0.06). Patella bone lead concentration was not consistently associated with performance on the tests. These data provide evidence suggesting that cumulative exposure to lead may result in worsened cognition among persons with PD. Copyright © 2012 Movement Disorders Society.

Case-control study of genus-beta human papillomaviruses in plucked eyebrow hairs and cutaneous squamous cell carcinoma.

PubMed

Iannacone, Michelle R; Gheit, Tarik; Pfister, Herbert; Giuliano, Anna R; Messina, Jane L; Fenske, Neil A; Cherpelis, Basil S; Sondak, Vernon K; Roetzheim, Richard G; Silling, Steffi; Pawlita, Michael; Tommasino, Massimo; Rollison, Dana E

2014-05-01

Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p < 0.05), and the association with SCC increased with the number of HPV types present, (≥ 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80; p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04-3.24). Additionally, when compared with the controls, the DNA prevalence in EBH was significantly higher among cases for 11 of the 25 genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development. © 2013 UICC.

Replication of CLU, CR1, and PICALM associations with alzheimer disease.

PubMed

Carrasquillo, Minerva M; Belbin, Olivia; Hunter, Talisha A; Ma, Li; Bisceglio, Gina D; Zou, Fanggeng; Crook, Julia E; Pankratz, V Shane; Dickson, Dennis W; Graff-Radford, Neill R; Petersen, Ronald C; Morgan, Kevin; Younkin, Steven G

2010-08-01

To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease. Follow-up case-control association study. The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota. Community-based patients of European descent with late-onset Alzheimer disease (LOAD) and controls without dementia who were seen at the Mayo clinics, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic in Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer Disease (NCRAD). A total of 1829 LOAD cases and 2576 controls were analyzed. The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD. Main Outcome Measure Clinical or pathology-confirmed diagnosis of LOAD. Odds ratios for CLU, CR1, and PICALM were 0.82, 1.15, and 0.80, respectively, comparable in direction and magnitude with those originally reported. P values were 8.6 x 10(-5), .014, and 1.3 x 10(-5), respectively; they remain significant even after Bonferroni correction for the 3 single-nucleotide polymorphisms tested. These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.

A case control study of association between cognition and functional capacity in schizophrenia.

PubMed

Narayanan, Sreelatha S; Bhatia, Triptish; Velligan, Dawn I; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2015-12-01

Cognitive functions are important prognostic factors for schizophrenia (SZ), while ability to perform activities of daily living are important measures of functional capacity. The relationship between cognition and functional capacity has not been tested extensively in India. To compare persons with SZ with controls on measures of cognition and functional capacity, and evaluate correlations between cognitive performance and functional capacity. Schizophrenia outpatients and controls without psychiatric illness (DSM IV) who completed the MATRICS Consensus Cognitive Battery and Functional Assessment Battery comprised of two tests from University of California San Diego (UCSD) Performance Based Skill Assessment (UPSA), one Test of Adaptive Behavior in Schizophrenia (TABS) and one test from University of California San Diego Performance Based Skill Assessment Brief edition (UPSA-B). Cognitive and functional domains were examined using regression analyses, with relevant covariates. Cases (N=51) though younger, were more educated than controls (N=41). Adjusting for education, controls performed better than cases in 3/7 cognitive and 4/5 domains of functional capacity but similarly in 'household management'. Among both cases and controls, cognitive measures of verbal learning and speed of processing overlapped with functional capacity (3 domains). Working memory was associated with one functional domain. Consistent with other studies, Indian patients with schizophrenia performed worse than controls on several domains of cognition and functional capacity; these domains were correlated. Speed of processing and verbal learning are most frequently associated with functional capacity indices and should be targeted to improve skills of daily living among persons with SZ. Copyright © 2015. Published by Elsevier B.V.

Human papillomavirus infection and spontaneous abortion: a case-control study performed in Mexico.

PubMed

Conde-Ferráez, Laura; Chan May, Alberto de A; Carrillo-Martínez, Jorge R; Ayora-Talavera, Guadalupe; González-Losa, María del Refugio

2013-10-01

To investigate if HPV cervical infection is associated with spontaneous abortion in a Mexican population. Case control study including 281 women from two Social Security Hospitals in Merida, Mexico. Cases were women with spontaneous abortion attending for curettage, and controls were pregnant women at term who attended for delivery. HPV molecular detection and typing of HPV 16, 18, 58 and 6/11 was performed on cervical samples, and TORCH serology IgM tests (against T. gondii, CMV, HSV) were performed on cases. Data were analyzed using Chi square, odds ratio and linear regression tests. HPV global prevalence was 19.8% (24.4% in cases and 15.2% in controls). HPV types 16 and 58 were the most frequently detected in both groups. Multiple HPV types concurrent infection were found in 31.4% of typified samples. Amongst cases 27.3% of HPV positive women reported at least one previous pregnancy loss; compared to 17.43% amongst HPV negative women. Nevertheless, HPV was not significantly associated with spontaneous or to repetitive abortion. Cases were 60.2% positive to any TORCH agent, although it was not significantly associated to referred miscarriage history. Spontaneous abortion was associated to a previous pregnancy loss and to women's age older than 35 years old. HPV infection was significantly associated to alcohol intake before pregnancy and to multiple sexual partners. HPV cervical infection was not associated with spontaneous abortion. HPV in spontaneous abortion and other adverse pregnancy outcomes merits further study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010.

PubMed

Seña, Arlene C; Moorman, Anne; Njord, Levi; Williams, Roxanne E; Colborn, James; Khudyakov, Yury; Drobenuic, Jan; Xia, Guo-Liang; Wood, Hattie; Moore, Zack

2013-07-01

Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. Outbreak investigation with case-control studies. Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.

Association Between Helicobacter pylori Infection and Risk of Periodontal Diseases in Han Chinese: A Case-Control Study

PubMed Central

Yang, Jing; Zhang, Qiang; Chen, Ming; Wu, Wu-zhou; Wang, Rong; Liu, Chang-jun; Li, Bei; Shi, Xin-li; Du, Han-song; Tan, Hua-bing

2016-01-01

Background This study was performed to test the association between Helicobacter pylori (HP) and periodontal disease (PD). Material/Methods This was a case-control study in a comprehensive hospital, including all patients with newly diagnosed PD between 2012 and 2014 as cases and all patients without PD as controls, thorough periodontal examinations. Those who tested positive for HP were examined by means of polymerase chain reaction. Single and multivariate logistic regression was used to analyze the data using SPSS 19.0 software. Results This case-control study included 212 Han Chinese non-smoking adults. The results indicated that HP-positive status significantly increased the risk of PD (2.63 times higher (odds ratio [OR]=2.63; 95% confidence interval [CI]=1.48–4.67). After adjustment for age, sex, level of education, physical exercise, body mass index, and history of alcohol and diabetes mellitus, this association remained significantly (OR=2.82, 95% CI=1.55–5.13). Conclusions PD might be associated with HP infection in adults and HP infection may be a significant and independent risk factor for PD. PMID:26753766

The need to scale up HIV indicator condition-guided testing for early case-finding: a case-control study in primary care.

PubMed

Joore, Ivo K; Twisk, Denise E; Vanrolleghem, Ann M; de Ridder, Maria; Geerlings, Suzanne E; van Bergen, Jan E A M; van den Broek, Ingrid V

2016-11-17

European guidelines recommend offering an HIV test to individuals who display HIV indicator conditions (ICs). We aimed to investigate the incidence of ICs in primary care reported in medical records prior to HIV diagnosis. We did a cross-sectional search in an electronic general practice database using a matched case-control design to identify which predefined ICs registered by Dutch GPs were most associated with an HIV-positive status prior to the time of diagnosis. We included 224 HIV cases diagnosed from 2009 to 2013, which were matched with 2,193 controls. Almost two thirds (n = 136, 60.7%) of cases were diagnosed with one or more ICs in the period up to five years prior to the index date compared to 18.7% (n = 411) of controls. Cases were more likely to have an IC than controls: in the one year prior to the index date, the odds ratio (OR) for at least one condition was 11.7 (95% CI: 8.3 to 16.4). No significant differences were seen in the strength of the association between HIV diagnosis and ICs when comparing genders, age groups or urbanisation levels. There is no indication that subgroups require a different testing strategy. Our study shows that there are opportunities for IC-guided testing in primary care. We recommend that IC-guided testing be more integrated in GPs' future guidelines and that education strategies be used to facilitate its implementation in daily practice.

PNPLA3 Association with Alcoholic Liver Disease in a Cohort of Heavy Drinkers.

PubMed

Kolla, Bhanu Prakash; Schneekloth, Terry D; Biernacka, Joanna; Shah, Vijay; Lazaridis, Konstantinos N; Geske, Jennifer; Karpyak, Victor

2018-02-21

Prior studies have established variation at the PNPLA3gene to be associated with a risk of developing alcoholic liver disease (ALD). We attempt to replicate this finding and other potential genetic variations previously associated with ALD utilizing a case-control design in a cohort of subjects with alcohol use disorders. This case-control study performed in a US clinical sample of heavy drinkers, replicates the previously reported association between ALD and rs738409 polymorphism in the PNPLA3gene in heavy drinkers. This association persisted after accounting for the subject's diabetes status. Patients of European ancestry with a history of ALD were identified (n = 169). Controls consisted of patients without ALD who were from the same cohorts and were ≥ 30 years of age, had lifetime total years drinking ≥20 and lifetime maximum drinks per day ≥12 (n = 259). Patients were genotyped for 40 candidate single nucleotide polymorphisms (SNPs) selected for the purpose of testing their association with ALD. The association of each SNP with ALD was tested using a logistic regression model, assuming log-additive allele effects. Bonferroni correction was applied and multivariable logistic regression models were used to account for relevant covariates. Age, sex, and body mass index (BMI) distributions were similar between cases and controls. Diabetes was more prevalent in the ALD cases. Three SNPs were associated with ALD at the nominal significance level (rs738409 in PNPLA3, P = 0.00029; rs3741559 in AQP2, P = 0.0185; rs4290029 in NVL, P = 0.0192); only PNPLA3rs738409 SNP was significant at the Bonferroni-corrected P-value threshold of 0.00125. Association results remained significant after adjustment for diabetes status. Our case-control study confirmed that PNPLA3 rs738409 SNP is associated with ALD. This is an important replication in a US clinical sample with control subjects who had long histories of alcohol consumption.

Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control study.

PubMed

Viney, K; Cavanaugh, J; Kienene, T; Harley, D; Kelly, P M; Sleigh, A; O'Connor, J; Mase, S

2015-05-01

To better inform local management of TB-diabetes collaborative activities, we aimed to determine the prevalence of diabetes among persons with and without TB and to determine the association between TB and diabetes in Kiribati, a Pacific Island nation. We compared consecutively enrolled TB cases to a group of randomly selected community controls without evidence of TB. Diabetes was diagnosed by HbA1c, and clinical and demographic data were collected. A tuberculin skin test was administered to controls. The chi-square test was used to assess significance in differences between cases and controls. We also calculated an odds ratio, with 95% confidence intervals, for the odds of diabetes among cases relative to controls. Unweighted multivariate logistic regression was performed to adjust for the effects of age and sex. A total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic diagnoses were new; this proportion was higher among controls (64.8%) than cases (46.5%). Five patients with TB were screened to detect one patient with diabetes. There is a strong association between TB and diabetes in Kiribati and bidirectional screening should be conducted in this setting. © 2015 John Wiley & Sons Ltd.

Aphrodisiac Use Associated with HIV Infection in Elderly Male Clients of Low-Cost Commercial Sex Venues in Guangxi, China: A Matched Case-Control Study

PubMed Central

Li, Guojian; Shen, Zhiyong; Zhang, Hongman; Lan, Guanghua; Feng, Xue; Lin, Rui; Abdullah, Abu S.; Wu, Zunyou; Shi, Cynthia X.

2014-01-01

Background Rising HIV infection rates have been observed among elderly people in Guangxi, China. Inexpensive aphrodisiacs are available for purchase in suburban and rural areas. This study aims to investigate the association between aphrodisiac use and increased HIV risk for middle-aged and elderly men in Guangxi. Methods A matched case-control study of aphrodisiac use-associated HIV infection was performed among male subjects over 50 years old who were clients of low-cost commercial sex venues in Guangxi. The cases were defined as clients who were HIV-positive and two controls were selected for each case. The cases and the controls were matched on the visited sex venue, age (±3 years), number of years of purchasing sex (±3 years), and educational attainment. Subjects were interviewed and tested for HIV. Paired t-test or McNemar Chi-squared test were used to compare the characteristics between the cases and controls. A stepwise conditional logistic regression was used to identify risk factors associated with HIV infection. Findings This study enrolled 103 cases and 206 controls. Aphrodisiac use (P = 0.02, odds ratio (OR) = 1.81, 95% CI = 1.08–3.04), never using condom during commercial sex encounter (P = 0.03, odds ratio (OR) = 1.82, 95% CI = 1.08–3.07), and lacking a stable partner (P = 0.03, odds ratio (OR) = 1.76, 95% CI = 1.05–2.98) were found to be risk factors for HIV infection among the study groups. For subjects reporting aphrodisiac use, the frequency of purchasing sex was positively correlated with the frequency of aphrodisiac use (r = 0.3; p = 0.02). Conclusions Aphrodisiac use was significantly associated with increased HIV infection risk in men over 50 years old who purchased commercial sex in the suburban and rural areas of Guangxi. Further research and interventions should address the links between aphrodisiac use, commercial sex work, condom use, and increased HIV transmission. PMID:25286369

Aphrodisiac use associated with HIV infection in elderly male clients of low-cost commercial sex venues in Guangxi, China: a matched case-control study.

PubMed

Tang, Zhenzhu; Wu, Xinghua; Li, Guojian; Shen, Zhiyong; Zhang, Hongman; Lan, Guanghua; Feng, Xue; Lin, Rui; Abdullah, Abu S; Wu, Zunyou; Shi, Cynthia X

2014-01-01

Rising HIV infection rates have been observed among elderly people in Guangxi, China. Inexpensive aphrodisiacs are available for purchase in suburban and rural areas. This study aims to investigate the association between aphrodisiac use and increased HIV risk for middle-aged and elderly men in Guangxi. A matched case-control study of aphrodisiac use-associated HIV infection was performed among male subjects over 50 years old who were clients of low-cost commercial sex venues in Guangxi. The cases were defined as clients who were HIV-positive and two controls were selected for each case. The cases and the controls were matched on the visited sex venue, age (±3 years), number of years of purchasing sex (±3 years), and educational attainment. Subjects were interviewed and tested for HIV. Paired t-test or McNemar Chi-squared test were used to compare the characteristics between the cases and controls. A stepwise conditional logistic regression was used to identify risk factors associated with HIV infection. This study enrolled 103 cases and 206 controls. Aphrodisiac use (P = 0.02, odds ratio (OR) = 1.81, 95% CI = 1.08-3.04), never using condom during commercial sex encounter (P = 0.03, odds ratio (OR) = 1.82, 95% CI = 1.08-3.07), and lacking a stable partner (P = 0.03, odds ratio (OR) = 1.76, 95% CI = 1.05-2.98) were found to be risk factors for HIV infection among the study groups. For subjects reporting aphrodisiac use, the frequency of purchasing sex was positively correlated with the frequency of aphrodisiac use (r = 0.3; p = 0.02). Aphrodisiac use was significantly associated with increased HIV infection risk in men over 50 years old who purchased commercial sex in the suburban and rural areas of Guangxi. Further research and interventions should address the links between aphrodisiac use, commercial sex work, condom use, and increased HIV transmission.

Study designs may influence results: the problems with questionnaire-based case-control studies on the epidemiology of glioma.

PubMed

Johansen, Christoffer; Schüz, Joachim; Andreasen, Anne-Marie Serena; Dalton, Susanne Oksbjerg

2017-03-28

Glioma is a rare brain tumour with a very poor prognosis and the search for modifiable factors is intense. We reviewed the literature concerning risk factors for glioma obtained in case-control designed epidemiological studies in order to discuss the influence of this methodology on the observed results. When reviewing the association between three exposures, medical radiation, exogenous hormone use and allergy, we critically appraised the evidence from both case-control and cohort studies. For medical radiation and hormone replacement therapy (HRT), questionnaire-based case-control studies appeared to show an inverse association, whereas nested case-control and cohort studies showed no association. For allergies, the inverse association was observed irrespective of study design. We recommend that the questionnaire-based case-control design be placed lower in the hierarchy of studies for establishing cause-and-effect for diseases such as glioma. We suggest that a state-of-the-art case-control study should, as a minimum, be accompanied by extensive validation of the exposure assessment methods and the representativeness of the study sample with regard to the exposures of interest. Otherwise, such studies cannot be regarded as 'hypothesis testing' but only 'hypothesis generating'. We consider that this holds true for all questionnaire-based case-control studies on cancer and other chronic diseases, although perhaps not to the same extent for each exposure-outcome combination.

Celiac disease serum markers and recurrent pregnancy loss.

PubMed

Sharshiner, Rita; Romero, Stephanie T; Bardsley, Tyler R; Branch, D Ware; Silver, Robert M

2013-12-01

Celiac disease has been associated with numerous unfavorable health outcomes, including pregnancy complications such as infertility, preterm birth, and preeclampsia. However, the association between celiac disease and recurrent pregnancy loss (RPL) remains uncertain. Our purpose was to compare serum markers of celiac disease in women with and without RPL. Therefore, we performed a case-control study of 116 women with unexplained recurrent pregnancy loss and 116 age-matched controls. Maternal sera were analyzed for immunoglobulin A (IgA) and immunoglobulin G (IgG) tissue transglutaminase (tTG) antibodies and endomysial (EM) antibodies. Groups were similar with regard to age, race and ethnicity, and BMI. One case and one control tested positive (≥20 Units) for IgA tTG antibodies and mean levels of IgA tTG antibodies were similar in cases and controls (5.5±2.86 versus 6.0±12.45; p=0.16). No cases or controls were positive for IgG tTG antibodies. However, cases had higher levels of IgG tTG antibody compared with controls (4.0±2.40 versus 3.3±1.30; p=0.0064). One subject (a control) tested positive for IgA EM antibodies and no subjects tested positive for IgG EM antibodies. In conclusion, positive results for tTG and EM antibodies were similar in women with and without RPL. Given these results, testing for occult celiac disease is not recommended in the evaluation of women with idiopathic RPL. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The ‘Pokemon’ (ZBTB7) Gene: No Evidence of Association with Sporadic Breast Cancer

PubMed Central

Salas, Antonio; Vega, Ana; Milne, Roger L.; García-Magariños, Manuel; Ruibal, Álvaro; Benítez, Javier; Carracedo, Ángel

2008-01-01

It has been proposed that the excess of familiar risk associated with breast cancer could be explained by the cumulative effect of multiple weakly predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon, has recently been identified as a critical factor in oncogenesis. This protein is encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in ZBTB7 are associated with breast cancer risk in a sample of cases and controls collected in hospitals from North and Central Spanish patients. We genotyped 15 SNPs in ZBTB7, including the flanking regions, with an average coverage of 1 SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of allele, genotype and haplotype frequencies between cases and controls did not reveal associations using Pearson’s chi-square test and a permutation procedure to correct for multiple test. In this, the first study of the ZBTB7 gene in relation to, sporadic breast cancer, we found no evidence of an association. PMID:21892298

Genome-wide association analysis accounting for environmental factors through propensity-score matching: application to stressful live events in major depressive disorder.

PubMed

Power, Robert A; Cohen-Woods, Sarah; Ng, Mandy Y; Butler, Amy W; Craddock, Nick; Korszun, Ania; Jones, Lisa; Jones, Ian; Gill, Michael; Rice, John P; Maier, Wolfgang; Zobel, Astrid; Mors, Ole; Placentino, Anna; Rietschel, Marcella; Aitchison, Katherine J; Tozzi, Federica; Muglia, Pierandrea; Breen, Gerome; Farmer, Anne E; McGuffin, Peter; Lewis, Cathryn M; Uher, Rudolf

2013-09-01

Stressful life events are an established trigger for depression and may contribute to the heterogeneity within genome-wide association analyses. With depression cases showing an excess of exposure to stressful events compared to controls, there is difficulty in distinguishing between "true" cases and a "normal" response to a stressful environment. This potential contamination of cases, and that from genetically at risk controls that have not yet experienced environmental triggers for onset, may reduce the power of studies to detect causal variants. In the RADIANT sample of 3,690 European individuals, we used propensity score matching to pair cases and controls on exposure to stressful life events. In 805 case-control pairs matched on stressful life event, we tested the influence of 457,670 common genetic variants on the propensity to depression under comparable level of adversity with a sign test. While this analysis produced no significant findings after genome-wide correction for multiple testing, we outline a novel methodology and perspective for providing environmental context in genetic studies. We recommend contextualizing depression by incorporating environmental exposure into genome-wide analyses as a complementary approach to testing gene-environment interactions. Possible explanations for negative findings include a lack of statistical power due to small sample size and conditional effects, resulting from the low rate of adequate matching. Our findings underscore the importance of collecting information on environmental risk factors in studies of depression and other complex phenotypes, so that sufficient sample sizes are available to investigate their effect in genome-wide association analysis. Copyright © 2013 Wiley Periodicals, Inc.

Effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction.

PubMed

Patel, Pragna; Bush, Tim; Overton, Turner; Baker, Jason; Hammer, John; Kojic, Erna; Conley, Lois; Henry, Keith; Brooks, John T

2012-01-01

This study examined the effect of abacavir on acute changes in biomarkers associated with cardiovascular dysfunction. Among the Study to Understand the Natural History of HIV/AIDS in the Era of Effective therapy (SUN) participants, we identified 25 individuals (cases) who were HLA-B5701-negative and who had ≥ 2 weeks without abacavir exposure at one visit and ≥ 2 weeks with abacavir exposure at the consecutive visit while maintaining viral suppression. We identified 43 individuals (controls) similarly unexposed and exposed to tenofovir. We assessed concentrations of prothrombin fragment F(1+2), D-dimer, high-sensitivity C-reactive protein, interleukin-8, intercellular adhesion molecule-1, vascular adhesion molecule-1, E-selectin, P-selectin, serum amyloid A and serum amyloid P. We examined the median percentage change of these biomarkers from the unexposed to exposed state among cases and controls compared with the expected assay variability using a sign test, and compared changes among cases with controls using the Wilcoxon rank-sum test. Baseline characteristics were similar between cases and controls: median age 45 versus 46 years, 80% versus 81% male, 64% versus 63% non-Hispanic White and median CD4(+) T-cell count 538 versus 601 cells/mm(3), respectively. Mean exposure times were 65 and 15 weeks for abacavir and tenofovir, respectively. We observed no significant changes in biomarkers from the unexposed to exposed state among cases or controls compared with the expected assay variability. We found that no biomarkers were significantly increased among cases compared with controls; however, prothrombin fragment F(1+2) was significantly lower among controls (P=0.035). In virologically suppressed contemporary HIV-infected patients, abacavir exposure was not associated with increases in biomarkers associated with increased cardiovascular risk.

Association of HK2 and NCK2 with Normal Tension Glaucoma in the Japanese Population

PubMed Central

Shi, Dong; Funayama, Tomoyo; Mashima, Yukihiko; Takano, Yoshimasa; Shimizu, Ai; Yamamoto, Kotaro; Mengkegale, MinGe; Miyazawa, Akiko; Yasuda, Noriko; Fukuchi, Takeo; Abe, Haruki; Ideta, Hidenao; Nishida, Kohji; Nakazawa, Toru; Richards, Julia E.; Fuse, Nobuo

2013-01-01

Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p = 0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p = 4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p = 0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p = 0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play in phenotypic variability. Our data suggest that HK2 may play an important role in NTG in the Japanese population. PMID:23349798

Interleukin 1 beta gene and risk of schizophrenia: detailed case-control and family-based studies and an updated meta-analysis.

PubMed

Shibuya, Masako; Watanabe, Yuichiro; Nunokawa, Ayako; Egawa, Jun; Kaneko, Naoshi; Igeta, Hirofumi; Someya, Toshiyuki

2014-01-01

Interleukin-1 beta (IL-1β) has been implicated in the pathophysiology of schizophrenia. To assess whether the IL1B gene confers increased susceptibility to schizophrenia, we conducted case-control and family-based studies and an updated meta-analysis. We tested the association between IL1B and schizophrenia in 1229 case-control and 112 trio samples using 12 markers, including common tagging single nucleotide variations (SNVs) and a rare non-synonymous variation detected by resequencing the coding regions. We also performed a meta-analysis of rs16944 using a total of 8724 case-control and 201 trio samples from 16 independent populations. We found no significant associations between any of the 12 SNVs examined and schizophrenia in either case-control or trio samples. Moreover, our meta-analysis results showed no significant association between the common SNV, rs16944, and schizophrenia. The present study does not support a role for IL1B in schizophrenia susceptibility.

TREAT (TREe-based Association Test)

Cancer.gov

TREAT is an R package for detecting complex joint effects in case-control studies. The test statistic is derived from a tree-structure model by recursive partitioning the data. Ultra-fast algorithm is designed to evaluate the significance of association between candidate gene and disease outcome

Utilizing population controls in rare-variant case-parent association tests.

PubMed

Jiang, Yu; Satten, Glen A; Han, Yujun; Epstein, Michael P; Heinzen, Erin L; Goldstein, David B; Allen, Andrew S

2014-06-05

There is great interest in detecting associations between human traits and rare genetic variation. To address the low power implicit in single-locus tests of rare genetic variants, many rare-variant association approaches attempt to accumulate information across a gene, often by taking linear combinations of single-locus contributions to a statistic. Using the right linear combination is key-an optimal test will up-weight true causal variants, down-weight neutral variants, and correctly assign the direction of effect for causal variants. Here, we propose a procedure that exploits data from population controls to estimate the linear combination to be used in an case-parent trio rare-variant association test. Specifically, we estimate the linear combination by comparing population control allele frequencies with allele frequencies in the parents of affected offspring. These estimates are then used to construct a rare-variant transmission disequilibrium test (rvTDT) in the case-parent data. Because the rvTDT is conditional on the parents' data, using parental data in estimating the linear combination does not affect the validity or asymptotic distribution of the rvTDT. By using simulation, we show that our new population-control-based rvTDT can dramatically improve power over rvTDTs that do not use population control information across a wide variety of genetic architectures. It also remains valid under population stratification. We apply the approach to a cohort of epileptic encephalopathy (EE) trios and find that dominant (or additive) inherited rare variants are unlikely to play a substantial role within EE genes previously identified through de novo mutation studies. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Decreased hospital length of stay associated with presentation of cases at morning report with librarian support

PubMed Central

Banks, Daniel E.; Shi, Runhua; Timm, Donna F.; Christopher, Kerri Ann; Duggar, David Charles; Comegys, Marianne; McLarty, Jerry

2007-01-01

Objective: The research sought to determine whether case discussion at residents' morning report (MR), accompanied by a computerized literature search and librarian support, affects hospital charges, length of stay (LOS), and thirty-day readmission rate. Methods: This case-control study, conducted from August 2004 to March 2005, compared outcomes for 105 cases presented at MR within 24 hours of admission to 19,210 potential matches, including cases presented at MR and cases not presented at MR. With matching criteria of patient age (± 5 years), identical primary diagnosis, and secondary diagnoses (within 3 additional diagnoses) using International Classification of Diseases (ICD-9) codes, 55 cases were matched to 136 controls. Statistical analyses included Student's t tests, chi-squared tests, and nonparametric methods. Results: LOS differed significantly between matched MR cases and controls (3 days vs. 5 days, P < 0.024). Median total hospital charges were $7,045 for the MR group and $10,663 for the control group. There was no difference in 30-day readmission rate between the 2 groups. Discussion/Conclusion: Presentation of a case at MR, followed by the timely dissemination of the results of an online literature review, resulted in a shortened LOS and lower hospital charges compared with controls. MR, in association with a computerized literature search guided by the librarians, was an effective means for introducing evidence-based medicine into patient care practices. PMID:17971885

Genome-wide study of resistant hypertension identified from electronic health records.

PubMed

Dumitrescu, Logan; Ritchie, Marylyn D; Denny, Joshua C; El Rouby, Nihal M; McDonough, Caitrin W; Bradford, Yuki; Ramirez, Andrea H; Bielinski, Suzette J; Basford, Melissa A; Chai, High Seng; Peissig, Peggy; Carrell, David; Pathak, Jyotishman; Rasmussen, Luke V; Wang, Xiaoming; Pacheco, Jennifer A; Kho, Abel N; Hayes, M Geoffrey; Matsumoto, Martha; Smith, Maureen E; Li, Rongling; Cooper-DeHoff, Rhonda M; Kullo, Iftikhar J; Chute, Christopher G; Chisholm, Rex L; Jarvik, Gail P; Larson, Eric B; Carey, David; McCarty, Catherine A; Williams, Marc S; Roden, Dan M; Bottinger, Erwin; Johnson, Julie A; de Andrade, Mariza; Crawford, Dana C

2017-01-01

Resistant hypertension is defined as high blood pressure that remains above treatment goals in spite of the concurrent use of three antihypertensive agents from different classes. Despite the important health consequences of resistant hypertension, few studies of resistant hypertension have been conducted. To perform a genome-wide association study for resistant hypertension, we defined and identified cases of resistant hypertension and hypertensives with treated, controlled hypertension among >47,500 adults residing in the US linked to electronic health records (EHRs) and genotyped as part of the electronic MEdical Records & GEnomics (eMERGE) Network. Electronic selection logic using billing codes, laboratory values, text queries, and medication records was used to identify resistant hypertension cases and controls at each site, and a total of 3,006 cases of resistant hypertension and 876 controlled hypertensives were identified among eMERGE Phase I and II sites. After imputation and quality control, a total of 2,530,150 SNPs were tested for an association among 2,830 multi-ethnic cases of resistant hypertension and 876 controlled hypertensives. No test of association was genome-wide significant in the full dataset or in the dataset limited to European American cases (n = 1,719) and controls (n = 708). The most significant finding was CLNK rs13144136 at p = 1.00x10-6 (odds ratio = 0.68; 95% CI = 0.58-0.80) in the full dataset with similar results in the European American only dataset. We also examined whether SNPs known to influence blood pressure or hypertension also influenced resistant hypertension. None was significant after correction for multiple testing. These data highlight both the difficulties and the potential utility of EHR-linked genomic data to study clinically-relevant traits such as resistant hypertension.

Factors associated with negative histamine control for penicillin allergy skin testing in the inpatient setting.

PubMed

Geng, Bob; Thakor, Ami; Clayton, Elisabeth; Finkas, Lindsay; Riedl, Marc A

2015-07-01

Identification of factors adversely affecting the utility of allergy skin testing is important in optimizing patient care. Inpatient penicillin skin test data from 1997 through 2007 demonstrate that up to 20% of attempted penicillin skin tests are indeterminate owing to a negative histamine test response, despite exclusion of H1 antagonists. Critical illness, vasopressors, steroid use, and psychotropic medications have been postulated to influence outcomes, but large studies are lacking. To identify factors associated with a negative histamine test response for the inpatient setting. Fifty-two cases were identified with a negative histamine response after penicillin skin testing in the absence of antihistamine therapy for 72 hours before testing. One hundred twenty-five controls with a normal histamine response were randomly selected from same population. Independent variables assessed included stay in the intensive care unit (ICU), skin color, diabetes, age, use of vasopressors, H2 blocker, steroids, other immunosuppressive drugs, thyroid replacement, proton pump inhibitors, diuretics, 5 categories of psychotropic medications, and amiodarone. Mean age was 68 years for cases vs 60 years for controls (P = .002). Bivariate analysis showed ICU stay was more frequent in cases than in controls (73.1% vs 33.6%, P < .001). Regression analysis yielded odds ratios (ORs) of 8.18 (95% confidence interval 3.22-20.76) for ICU status, 3.76 (1.30-10.92) for systemic corticosteroids, and 4.90 (1.17-20.62) for H2 blockers as associated with lack of histamine response. For every additional year in age, there was increase in the OR of 1.04 (1.01-1.07). Regression analysis supports ICU stay during skin testing as associated with a high OR for a negative histamine response independent of age. Systemic corticosteroids, H2 blockers, and older age are associated with a significant OR for a negative histamine response. This is one of largest studies on factors associated with a negative histamine response for the inpatient setting and has significant implications for clinical practice. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada.

PubMed

Skowronski, Danuta M; De Serres, Gaston; Crowcroft, Natasha S; Janjua, Naveed Z; Boulianne, Nicole; Hottes, Travis S; Rosella, Laura C; Dickinson, James A; Gilca, Rodica; Sethi, Pam; Ouhoummane, Najwa; Willison, Donald J; Rouleau, Isabelle; Petric, Martin; Fonseca, Kevin; Drews, Steven J; Rebbapragada, Anuradha; Charest, Hugues; Hamelin, Marie-Eve; Boivin, Guy; Gardy, Jennifer L; Li, Yan; Kwindt, Trijntje L; Patrick, David M; Brunham, Robert C

2010-04-06

In late spring 2009, concern was raised in Canada that prior vaccination with the 2008-09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association. (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008-09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33-0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases. Prior receipt of 2008-09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring-summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered.

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case-control study.

PubMed

Colombara, Danny V; Manhart, Lisa E; Carter, Joseph J; Hawes, Stephen E; Weiss, Noel S; Hughes, James P; Barnett, Matt J; Goodman, Gary E; Smith, Jennifer S; Qiao, You-Lin; Galloway, Denise A

2015-12-01

To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. We performed a nested case-control study, testing serum from the carotene and retinol efficacy trial, conducted 1985-2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n = 200) were frequency-matched with controls (n = 200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze/thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (p corrected >0.10 for all trend tests; odds ratio (OR) range 0.72-1.09, p corrected >0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (p corrected ≥0.10 for all trend tests; OR range 0.25-2.54, p > 0.05 for all OR > 1), but the number of persons with serologic evidence of these infections was small. Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person's risk of lung cancer in Western smoking populations.

Association of ALOX5AP with ischemic stroke: a population-based case-control study.

PubMed

Kaushal, Ritesh; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Flaherty, Matthew; Moomaw, Charles; Sekar, Padmini; Kissela, Brett; Kleindorfer, Dawn; Chakraborty, Ranajit; Broderick, Joseph; Deka, Ranjan; Woo, Daniel

2007-06-01

Arachidonate 5-lipoxygenase activating protein (ALOX5AP) has been reported to demonstrate linkage and association with ischemic stroke and myocardial infarction. However, replication studies have been conflicting and to date, a significant proportion of blacks have not been studied. We prospectively recruited cases of ischemic stroke from all 16 hospitals in the Greater Cincinnati/Northern Kentucky region and demographically matched them to stroke-free population-based controls. Single nucleotide polymorphisms (SNPs) were selected based on association with ischemic stroke in prior studies. Allelic, genotypic and haplotypic association testing was performed using HAPLOVIEW. Multiple logistic regression was used to control for the presence of traditional risk factors including hypertension, diabetes, hypercholesterolemia and smoking. A total of 357 cases and 482 controls were genotyped. The SNPs, rs9579646 and rs4769874 were found to be significantly associated at both allelic (P=0.019 and P<10(-4), respectively) and genotypic level with ischemic stroke among whites after correction for multiple testing. Haplotype association was identified with ischemic stroke as well as ischemic stroke subtypes among whites. Although an overall haplotype association with ischemic stroke was identified among blacks no evidence of association among individual haplotypes, alleles or genotypes were observed. Allele frequencies for the SNPs examined were markedly different among whites and blacks. In conclusion, we report significant association of variants of ALOX5AP with ischemic stroke and ischemic stroke subtypes among whites. No significant association was identified among blacks.

Challenges with controlling varicella in prison settings: Experience of California, 2010–2011

PubMed Central

Leung, Jessica; Lopez, Adriana S.; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H.; Preas, Christopher P.; Cosentino, Giorgio; Bialek, Stephanie R.; Marin, Mona

2015-01-01

We describe the epidemiology of varicella in one state prison in California during 2010–2011, control measures implemented, and associated costs. Eleven varicella cases were reported, 9 associated with 2 outbreaks. One outbreak consisted of 3 cases and the second consisted of 6 cases with 2 generations of spread. Among exposed inmates serologically tested, 98% (643/656) were VZV sero-positive. The outbreaks resulted in >1,000 inmates exposed, 444 staff exposures, and >$160,000 in costs. We documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary for managing cases and outbreaks. PMID:25201912

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

PubMed

Park, Daniel E; Baggett, Henry C; Howie, Stephen R C; Shi, Qiyuan; Watson, Nora L; Brooks, W Abdullah; Deloria Knoll, Maria; Hammitt, Laura L; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G; Thea, Donald M; Ahmed, Dilruba; Antonio, Martin; Baillie, Vicky L; DeLuca, Andrea N; Driscoll, Amanda J; Fu, Wei; Gitahi, Caroline W; Olutunde, Emmanuel; Higdon, Melissa M; Hossain, Lokman; Karron, Ruth A; Maiga, Abdoul Aziz; Maloney, Susan A; Moore, David P; Morpeth, Susan C; Mwaba, John; Mwenechanya, Musaku; Prosperi, Christine; Sylla, Mamadou; Thamthitiwat, Somsak; Zeger, Scott L; Feikin, Daniel R

2017-06-15

There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia—Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii

PubMed Central

Baggett, Henry C.; Howie, Stephen R. C.; Shi, Qiyuan; Watson, Nora L.; Brooks, W. Abdullah; Deloria Knoll, Maria; Hammitt, Laura L.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.; Thea, Donald M.; Ahmed, Dilruba; Antonio, Martin; Baillie, Vicky L.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fu, Wei; Gitahi, Caroline W.; Olutunde, Emmanuel; Higdon, Melissa M.; Hossain, Lokman; Karron, Ruth A.; Maiga, Abdoul Aziz; Maloney, Susan A.; Moore, David P.; Morpeth, Susan C.; Mwaba, John; Mwenechanya, Musaku; Prosperi, Christine; Sylla, Mamadou; Thamthitiwat, Somsak; Zeger, Scott L.; Feikin, Daniel R.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Wangeci Kagucia, E.; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Abdullah Brooks, W.; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Mahomed, Nasreen; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne

2017-01-01

Abstract Background. There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods. In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. Results. Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)–positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. Conclusions. There is evidence for an association between H. influenzae colonization density and H. influenzae–confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings. PMID:28575367

Segment-Wise Genome-Wide Association Analysis Identifies a Candidate Region Associated with Schizophrenia in Three Independent Samples

PubMed Central

Rietschel, Marcella; Mattheisen, Manuel; Breuer, René; Schulze, Thomas G.; Nöthen, Markus M.; Levinson, Douglas; Shi, Jianxin; Gejman, Pablo V.; Cichon, Sven; Ophoff, Roel A.

2012-01-01

Recent studies suggest that variation in complex disorders (e.g., schizophrenia) is explained by a large number of genetic variants with small effect size (Odds Ratio∼1.05–1.1). The statistical power to detect these genetic variants in Genome Wide Association (GWA) studies with large numbers of cases and controls (∼15,000) is still low. As it will be difficult to further increase sample size, we decided to explore an alternative method for analyzing GWA data in a study of schizophrenia, dramatically reducing the number of statistical tests. The underlying hypothesis was that at least some of the genetic variants related to a common outcome are collocated in segments of chromosomes at a wider scale than single genes. Our approach was therefore to study the association between relatively large segments of DNA and disease status. An association test was performed for each SNP and the number of nominally significant tests in a segment was counted. We then performed a permutation-based binomial test to determine whether this region contained significantly more nominally significant SNPs than expected under the null hypothesis of no association, taking linkage into account. Genome Wide Association data of three independent schizophrenia case/control cohorts with European ancestry (Dutch, German, and US) using segments of DNA with variable length (2 to 32 Mbp) was analyzed. Using this approach we identified a region at chromosome 5q23.3-q31.3 (128–160 Mbp) that was significantly enriched with nominally associated SNPs in three independent case-control samples. We conclude that considering relatively wide segments of chromosomes may reveal reliable relationships between the genome and schizophrenia, suggesting novel methodological possibilities as well as raising theoretical questions. PMID:22723893

Using public control genotype data to increase power and decrease cost of case-control genetic association studies.

PubMed

Ho, Lindsey A; Lange, Ethan M

2010-12-01

Genome-wide association (GWA) studies are a powerful approach for identifying novel genetic risk factors associated with human disease. A GWA study typically requires the inclusion of thousands of samples to have sufficient statistical power to detect single nucleotide polymorphisms that are associated with only modest increases in risk of disease given the heavy burden of a multiple test correction that is necessary to maintain valid statistical tests. Low statistical power and the high financial cost of performing a GWA study remains prohibitive for many scientific investigators anxious to perform such a study using their own samples. A number of remedies have been suggested to increase statistical power and decrease cost, including the utilization of free publicly available genotype data and multi-stage genotyping designs. Herein, we compare the statistical power and relative costs of alternative association study designs that use cases and screened controls to study designs that are based only on, or additionally include, free public control genotype data. We describe a novel replication-based two-stage study design, which uses free public control genotype data in the first stage and follow-up genotype data on case-matched controls in the second stage that preserves many of the advantages inherent when using only an epidemiologically matched set of controls. Specifically, we show that our proposed two-stage design can substantially increase statistical power and decrease cost of performing a GWA study while controlling the type-I error rate that can be inflated when using public controls due to differences in ancestry and batch genotype effects.

Association of β-defensin copy number and psoriasis in three cohorts of European origin

PubMed Central

Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John AL

2012-01-01

A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study we attempted to replicate that finding in larger new cohorts from Erlangen (N = 2017) and Michigan (N = 5412), using improved methods for beta-defensin copy number determination based on the paralog ratio test (PRT), and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (p = 5.5 × 10−4, OR = 1.25). We also find that the association is replicated in 2616 cases and 2526 controls from Michigan, although at reduced significance (p = 0.014), but not in new samples from Erlangen (1396 cases and 621 controls, p = 0.38). Meta-analysis across all cohorts suggests a nominally significant association (p = 6.6 × 10−3/2 × 10−4) with an effect size (OR = 1.081) much lower than found in the discovery study (OR = 1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association. PMID:22739795

STAT4 and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus

PubMed Central

Remmers, Elaine F.; Plenge, Robert M.; Lee, Annette T.; Graham, Robert R.; Hom, Geoffrey; Behrens, Timothy W.; de Bakker, Paul I.W.; Le, Julie M.; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L.; Booty, Matthew G.; Carulli, John P.; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V.; Amos, Christopher I.; Criswell, Lindsey A.; Seldin, Michael F.; Kastner, Daniel L.

2009-01-01

BACKGROUND Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. METHODS We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. RESULTS A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P = 2.81×10-7; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P = 0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P = 1.87×10-9; odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. CONCLUSIONS A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. PMID:17804842

STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus.

PubMed

Remmers, Elaine F; Plenge, Robert M; Lee, Annette T; Graham, Robert R; Hom, Geoffrey; Behrens, Timothy W; de Bakker, Paul I W; Le, Julie M; Lee, Hye-Soon; Batliwalla, Franak; Li, Wentian; Masters, Seth L; Booty, Matthew G; Carulli, John P; Padyukov, Leonid; Alfredsson, Lars; Klareskog, Lars; Chen, Wei V; Amos, Christopher I; Criswell, Lindsey A; Seldin, Michael F; Kastner, Daniel L; Gregersen, Peter K

2007-09-06

Rheumatoid arthritis is a chronic inflammatory disease with a substantial genetic component. Susceptibility to disease has been linked with a region on chromosome 2q. We tested single-nucleotide polymorphisms (SNPs) in and around 13 candidate genes within the previously linked chromosome 2q region for association with rheumatoid arthritis. We then performed fine mapping of the STAT1-STAT4 region in a total of 1620 case patients with established rheumatoid arthritis and 2635 controls, all from North America. Implicated SNPs were further tested in an independent case-control series of 1529 patients with early rheumatoid arthritis and 881 controls, all from Sweden, and in a total of 1039 case patients and 1248 controls from three series of patients with systemic lupus erythematosus. A SNP haplotype in the third intron of STAT4 was associated with susceptibility to both rheumatoid arthritis and systemic lupus erythematosus. The minor alleles of the haplotype-defining SNPs were present in 27% of chromosomes of patients with established rheumatoid arthritis, as compared with 22% of those of controls (for the SNP rs7574865, P=2.81x10(-7); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.32). The association was replicated in Swedish patients with recent-onset rheumatoid arthritis (P=0.02) and matched controls. The haplotype marked by rs7574865 was strongly associated with lupus, being present on 31% of chromosomes of case patients and 22% of those of controls (P=1.87x10(-9); odds ratio for having the risk allele in chromosomes of patients vs. those of controls, 1.55). Homozygosity of the risk allele, as compared with absence of the allele, was associated with a more than doubled risk for lupus and a 60% increased risk for rheumatoid arthritis. A haplotype of STAT4 is associated with increased risk for both rheumatoid arthritis and systemic lupus erythematosus, suggesting a shared pathway for these illnesses. Copyright 2007 Massachusetts Medical Society.

Survey on association between Mycoplasma hominis endocervical infection and spontaneous abortion using Polymerase Chain Reaction.

PubMed

Farhadifar, Fariba; Khodabandehloo, Mazaher; Ramazanzadeh, Rashid; Rouhi, Samaneh; Ahmadi, Amjad; Ghaderi, Ebrahim; Roshani, Daem; Soofizadeh, Nasrin; Rezzaii, Masoomeh

2016-03-01

Mycoplasma infections are suggested as etiology of adverse pregnancy outcomes. The aim of this study was to evaluate the association of Mycoplasma hominis (M. hominis) infection and spontaneous abortion among pregnant women. In this case-control study that was conducted from August 2012 to January 2013, totally, 109 women were included with spontaneous abortion with gestational ages of 10-20 weeks (Cases), and 109 women with normal pregnancy with gestational ages between 20-37 weeks (Controls) in Sanandaj, Iran. Using specific primers and extracted DNA from endocervical swabs, a PCR test was conducted for detection of M. hominis infection in women. For comparison of qualitative and quantitative variables, independent Fisher tests were used and p<0.05 was considered significant. The total frequency of M. hominis infection was 6 (2.75%) in women. The frequency of M. hominis infection was 2 (1.83%) in the case group (spontaneous abortion) and 4 (3.66%) in the control group, respectively. In both case and control groups, no association was seen between M.hominis infection and spontaneous abortion (OR=0. 49, CI 95%: 0.08-2.73, p=0. 683). M. hominis was positive in the genital tract of some pregnant women, but it was not associated with spontaneous abortion. However, to prevent adverse pregnancy outcomes in women, foetus and neonate, routine screening and treatment for the genital Mycoplasma is recommended.

A genetic study of the ghrelin and growth hormone secretagogue receptor (GHSR) genes and stature.

PubMed

Gueorguiev, M; Lecoeur, C; Benzinou, M; Mein, C A; Meyre, D; Vatin, V; Weill, J; Heude, B; Grossman, A B; Froguel, P; Korbonits, M

2009-01-01

Growth and nutrition are interrelated and influenced by multiple genetic and environmental factors. We studied whether common variants in ghrelin and ghrelin receptor (GHSR) genes could play a role in stature variation in the general population and in families ascertained for obesity. Selected tagging SNPs in the ghrelin and GHSR genes were genotyped in 263 Caucasian families recruited for childhood obesity (1,275 subjects), and in 287 families from a general population (1,072 subjects). We performed familial testing for associations in the entire population and in a sub-set of the samples selected for a case-control study. In the case-control study for height (cases were selected from the obese cohort with mean ZH = 3.17 +/- 0.15 confidence interval (CI) versus controls with mean ZH 0.14 +/- 0.09), we found an association with a 2 base-pair intronic deletion in the GHSR gene (rs10618418) (p = 0.006, odds ratio (OR) 1.86, 95% CI [1.26;2.74] under additive model), although when adjusting for BMI, the association disappeared (p = 0.06). Individuals carrying no deletion or who were heterozygous were significantly more frequent among the tall obese population (52% vs. 36% in controls, p = 0.007, OR 1.97, 95%CI [1.22;3.18]). However, the association was not maintained after correcting for multiple testing. Familial association testing of the ghrelin and GHSR genes and their interaction testing failed to show that any combination of SNPs had any significant effect. Thus, our results suggest that common variants of the ghrelin and GHSR genes are not major contributors to height variation in a French population.

Toxoplasma gondii seroprevalence and association with equine protozoal myeloencephalitis: A case-control study of Californian horses.

PubMed

James, K E; Smith, W A; Packham, A E; Conrad, P A; Pusterla, N

2017-06-01

While toxoplasmosis is not commonly considered a clinical disease of equines, previous seroprevalence studies have reported differing background rates of Toxoplasma gondii infection in horses globally. The objective of this study was to evaluate possible associations between T. gondii seroprevalence and clinical signs of equine protozoal myeloencephalitis (EPM) in horses. Using a case-control study design, 720 Californian horses with neurologic signs compatible with EPM were compared to healthy, non-neurologic horses for the presence of T. gondii antibodies (using indirect fluorescent antibody tests [IFAT]). Toxoplasma gondii seroprevalence among cases and controls was determined at standard serum cut-offs: 40, 80, 160, 320, and 640. At a T. gondii titre cut-off of 320, horses with clinical signs compatible with EPM had 3.55 times the odds of a seropositive test compared to those without clinical signs (P<0.01) when adjusted for covariates. When restricted to the autumn season and at the same titre cut-off, an EPM suspect horse had 6.4 times the odds of testing seropositive to T. gondii, compared to non-neurologic horses. The association between high T. gondii titres and clinical signs compatible with EPM is potentially reflective of toxoplasmosis in equines. Serologic testing of cerebrospinal fluid and isolation of T. gondii in EPM suspect cases should be considered. Future studies investigating the relationship between T. gondii and EPM are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intrahousehold resource allocation and child growth in Mozambique: an ethnographic case-control study.

PubMed

Pfeiffer, J; Gloyd, S; Ramirez Li, L

2001-07-01

This study examines the effect of intrahousehold cash income control and decision-making patterns on child growth in the rural town of Sussundenga in Manica Province, Mozambique. A case-control study design was used to examine the influence of men's and women's disaggregated cash incomes on child growth. The research tested whether greater maternal share of household cash income was associated with (1) increased maternal decision-making and bargaining power in the household, and (2) better child growth. Fifty case households, with children 1-4 years old exhibiting poor growth, were matched with 50 control households of similar socioeconomic status in which all children under five demonstrated healthy growth. Data were gathered on gender-specific income generation and expenditure, specific intrahousehold allocation processes, diet, and sociodemographic variables using a formal survey. Key informant interviews, focus groups, and observation over one year provided ethnographic context for the case-control findings. Case-control differences were analyzed using McNemar's test, paired t-test, and conditional logistic regression. In spite of matching households for socioeconomic status, control household incomes were still slightly greater than cases. Male spouse income was also higher among controls while maternal income, and maternal proportion of household income, were not significantly different. Household meat, fish and poultry consumption, and maternal education were significantly greater among control households than cases. Greater maternal share of household income was not associated with greater maternal decision-making around cash. However, mothers must spend what little cash they earn on daily food supplies and usually request additional cash from spouses to cover these costs. There is evidence that if mothers earn enough to cover these socially prescribed costs, they can spend cash for other needs. Above this threshold, women's earnings may confer more bargaining power. The research also revealed a nuclearization of households, attenuation of community bonds of mutual aid, and increasing importance of cash for survival.

Association between Ureaplasma urealyticum endocervical infection and spontaneous abortion.

PubMed

Ahmadi, Amjad; Khodabandehloo, Mazaher; Ramazanzadeh, Rashid; Farhadifar, Fariba; Nikkhoo, Bahram; Soofizade, Nasrin; Rezaii, Masoome

2014-12-01

Ureaplasma urealyticum can colonize women genital tract and be isolated from the amniotic fluid of women with adverse pregnancy outcomes. The association of U. urealyticum with spontaneous abortion remains controversial. The aim of this study was to evaluate the frequency of U. urealyticum infection among pregnant women and its association with spontaneous abortion. In this case-control study we included 109 women with spontaneous abortion with gestation age between 10-20 weeks (Cases), and 109 women with normal pregnancy with gestation age between 20-30 weeks (Controls) in Sanandaj, Iran. Using specific primers and extracted DNA from endocervical swabs, a PCR test was conducted for detection of U. urealyticum in both women groups. Total prevalence of U. urealyticum infection in women was 26 out of 218 cases (11.92%). The prevalence of U. urealyticum infection was 18 out of 109 (16.5%) and 8 out of 109 (7.3%) in case (spontaneous abortion) and control groups, respectively. Using chi-square test, association between U. urealyticum infection and spontaneous abortion was statistically significant (P<0.05). Colonization of U. urealyticum in genital tract of women, and its asymptomatic feature in combination with other factors such as other microorganisms or cervical incompetence may induce spontaneous abortion. Further studies are needed to confirm this possibility.

Genetic polymorphisms in 85 DNA repair genes and bladder cancer risk.

PubMed

Michiels, Stefan; Laplanche, Agnès; Boulet, Thomas; Dessen, Philippe; Guillonneau, Bertrand; Méjean, Arnaud; Desgrandchamps, François; Lathrop, Mark; Sarasin, Alain; Benhamou, Simone

2009-05-01

Several defense mechanisms have been developed and maintained during the evolution to protect human cells against damage produced from exogenous or endogenous sources. We examined the associations between bladder cancer and a panel of 652 polymorphisms from 85 genes involved in maintenance of genetic stability [base excision repair, nucleotide excision repair, double-strand break repair (DSBR) and mismatch repair, as well as DNA synthesis and cell cycle regulation pathways] in 201 incident bladder cancer cases and 326 hospital controls. Score statistics were used to test differences in haplotype frequencies between cases and controls in an unconditional logistic regression model. To account for multiple testing, we associated to each P-value the expected proportion of false discoveries (q-value). Haplotype analysis revealed significant associations (P < 0.01) between bladder cancer and two genes (POLB and FANCA) with an associated q-value of 24%. A permutation test was also used to determine whether, in each pathway analyzed, there are more variants whose allelic frequencies are different between cases and controls as compared with what would be expected by chance. Differences were found for cell cycle regulation (P = 0.02) and to a lesser extent for DSBR (P = 0.05) pathways. These results hint to a few potential candidate genes; however, our study was limited by the small sample size and therefore low statistical power to detect associations. It is anticipated that genome-wide association studies will open new perspectives for interpretation of the results of extensive candidate gene studies such as ours.

Differences in Kaposi sarcoma-associated herpesvirus-specific and herpesvirus-non-specific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily.

PubMed

Amodio, Emanuele; Goedert, James J; Barozzi, Patrizia; Riva, Giovanni; Firenze, Alberto; Bonura, Filippa; Viviano, Enza; Romano, Nino; Luppi, Mario

2011-10-01

Kaposi sarcoma (KS) might develop because of incompetent immune responses, both non-specifically and specifically against the KS-associated herpesvirus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS) and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (enzyme-linked immunospot [Elispot]) responses to KSHV-latency-associated nuclear antigen (LANA), KSHV-K8.1 and CMV/Epstein-Barr virus (EBV) peptide pools. The forearm and thigh of each participant was also tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). A KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS) and two (13%) seronegative controls. All four cases with KSHV-LANA responses had current KS lesions, whereas five of six cases with KSHV-K8.1 responses had no lesions (P = 0.048). No case responded to both LANA and K8.1. Compared with the seronegative controls, the risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55-0.94, P = 0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02-1.80, P = 0.04) and tended to be increased fivefold per KSHV Elispot response (OR 5.13, 95% CI 0.86-30.77, P = 0.07). Compared with KSHV seropositives (without KS), the risk for classic KS was reduced fivefold (OR 0.20, CI 0.03-0.77, P = 0.04) per KSHV response. The CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and KSHV-non-specific immunity is associated with classic KS. This might clarify why Kaposi sarcoma responds to immune reconstitution. © 2011 Japanese Cancer Association and this article is a US Government work and is in the public domain in the USA.

Replication of prostate cancer risk loci in a Japanese case-control association study.

PubMed

Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

2009-10-07

Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

Autonomic Dysfunction and Risk Factors Associated with Trypanosoma cruzi Infection among Children in Arequipa, Peru

PubMed Central

Bowman, Natalie M.; Kawai, Vivian; Gilman, Robert H.; Bocangel, Cesar; Galdos-Cardenas, Gerson; Cabrera, Lilia; Levy, Michael Z.; Cornejo del Carpio, Juan Geny; Delgado, Freddy; Rosenthal, Lauren; Pinedo-Cancino, Vivian V.; Steurer, Francis; Seitz, Amy E.; Maguire, James H.; Bern, Caryn

2011-01-01

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20–30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections. PMID:21212207

Caregiver's depressive symptoms and asthma control in children from an underserved community.

PubMed

Rioseco, Andrea; Serrano, Carolina; Celedón, Juan C; Padilla, Oslando; Puschel, Klaus; Castro-Rodriguez, Jose A

2017-12-01

Caregiver's or maternal depression has been associated with increased asthma morbidity in children from prosperous nations, but little is known about this link in low and middle-income countries. To examine if caregiver's depressive symptoms are associated with poor asthma control and abnormal immune responses in school-aged children. Case-control study of 87 asthmatic children (aged 4-11 years) attending a primary care clinic in an underserved area of Santiago (Chile). Cases were children with poor asthma control (Child Asthma Control Test [cACT] <20 points) and controls were children with adequate asthma control (cACT ≥20 points). The Beck Depression Inventory-II (BDI) and a locally validated family health vulnerability test (SALUFAM) were used to assess caregivers' depression and family health vulnerability. Serum from participating children was assayed for IFN-γ, IL-4, IL-13, TGF-β, cortisol, and total IgE. The mean (SD) age of study participants was 8.23 (2.15 years), and 55.2% were females. Use of inhaled corticosteroids (ICS), family health vulnerability, and caregiver's depressive symptoms were significantly more common in cases than in controls (65.4% vs. 34.6%, p = 0.003; 41.3% vs. 24.8%, p = 0.07; and 39.1% vs. 19.5%, p = 0.04, respectively). There was no significant difference in the level of any serum biomarkers between groups. In a multivariate analysis, only ICS use was significantly associated with better asthma control (OR = 3.56 [1.34-9.48], p = 0.01). Presence of caregiver's depressive symptoms is associated with poor asthma control among children from an underserved community, but this association was no longer significant after accounting for ICS use.

Risk factors for explantation due to infection after sacral neuromodulation: a multicenter retrospective case-control study.

PubMed

Myer, Emily N B; Petrikovets, Andrey; Slocum, Paul D; Lee, Toy Gee; Carter-Brooks, Charelle M; Noor, Nabila; Carlos, Daniela M; Wu, Emily; Van Eck, Kathryn; Fashokun, Tola B; Yurteri-Kaplan, Ladin; Chen, Chi Chiung Grace

2018-04-07

Sacral neuromodulation is an effective therapy for overactive bladder, urinary retention, and fecal incontinence. Infection after sacral neurostimulation is costly and burdensome. Determining optimal perioperative management strategies to reduce the risk of infection is important to reduce this burden. We sought to identify risk factors associated with sacral neurostimulator infection requiring explantation, to estimate the incidence of infection requiring explantation, and identify associated microbial pathogens. This is a multicenter retrospective case-control study of sacral neuromodulation procedures completed from Jan. 1, 2004, through Dec. 31, 2014. We identified all sacral neuromodulation implantable pulse generator implants as well as explants due to infection at 8 participating institutions. Cases were patients who required implantable pulse generator explantation for infection during the review period. Cases were included if age ≥18 years old, follow-up data were available ≥30 days after implantable pulse generator implant, and the implant was performed at the institution performing the explant. Two controls were matched to each case. These controls were the patients who had an implantable pulse generator implanted by the same surgeon immediately preceding and immediately following the identified case who met inclusion criteria. Controls were included if age ≥18 years old, no infection after implantable pulse generator implant, follow-up data were available ≥180 days after implant, and no explant for any reason <180 days from implant. Controls may have had an explant for reasons other than infection at >180 days after implant. Fisher exact test (for categorical variables) and Student t test (for continuous variables) were used to test the strength of the association between infection and patient and surgery characteristics. Significant variables were then considered in a multivariable logistic regression model to determine risk factors independently associated with infection. Over a 10-year period at 8 academic institutions, 1930 sacral neuromodulator implants were performed by 17 surgeons. In all, 38 cases requiring device explant for infection and 72 corresponding controls were identified. The incidence of infection requiring explant was 1.97%. Hematoma formation (13% cases, 0% controls; P = .004) and pocket depth of ≥3 cm (21% cases, 0% controls; P = .031) were independently associated with an increased risk of infection requiring explant. On multivariable regression analysis controlling for significant variables, both hematoma formation (P = .006) and pocket depth ≥3 cm (P = .020, odds ratio 3.26; 95% confidence interval, 1.20-8.89) remained significantly associated with infection requiring explant. Of the 38 cases requiring explant, 32 had cultures collected and 24 had positive cultures. All 5 cases with a hematoma had a positive culture (100%). Of the 4 cases with a pocket depth ≥3 cm, 2 had positive cultures, 1 had negative cultures, and 1 had a missing culture result. The most common organism identified was methicillin-resistant Staphylococcus aureus (38%). Infection after sacral neuromodulation requiring device explant is low. The most common infectious pathogen identified was methicillin-resistant S aureus. Demographic and health characteristics did not predict risk of explant due to infection, however, having a postoperative hematoma or a deep pocket ≥3 cm significantly increased the risk of explant due to infection. These findings highlight the importance of meticulous hemostasis as well as ensuring the pocket depth is <3 cm at the time of device implant. Copyright © 2018 Elsevier Inc. All rights reserved.

Challenges with controlling varicella in prison settings: experience of California, 2010 to 2011.

PubMed

Leung, Jessica; Lopez, Adriana S; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H; Preas, Christopher P; Cosentino, Giorgio; Bialek, Stephanie R; Marin, Mona

2014-10-01

This article describes the epidemiology of varicella in one state prison in California during 2010 and 2011, control measures implemented, and associated costs. Eleven varicella cases were reported, of which nine were associated with two outbreaks. One outbreak consisted of three cases and the second consisted of six cases with two generations of spread. Among exposed inmates serologically tested, 98% (643/656) were varicella-zoster virus seropositive. The outbreaks resulted in > 1,000 inmates exposed, 444 staff exposures, and > $160,000 in costs. The authors documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary to manage cases and outbreaks. © The Author(s) 2014.

The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age

PubMed Central

Del Brutto, Oscar H.; Issa, Naoum P.; Salgado, Perla; Del Brutto, Victor J.; Zambrano, Mauricio; Lama, Julio; García, Héctor H.

2017-01-01

Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case–control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6–14.9, P < 0.0021). Stratification of pairs according to tertiles of age revealed an age-related trend in this association, which became significant only in those aged ≥ 68 years (P = 0.027). Only five cases and one control had recurrent seizures (P = 0.221); three of these five cases had hippocampal atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop. PMID:28077750

Differences in Kaposi sarcoma-associated herpesvirus-specific and –nonspecific immune responses in classic Kaposi sarcoma cases and matched controls in Sicily

PubMed Central

Amodio, Emanuele; Goedert, James J.; Barozzi, Patrizia; Riva, Giovanni; Firenze, Alberto; Bonura, Filippa; Viviano, Enza; Romano, Nino; Luppi, Mario

2011-01-01

SUMMARY Kaposi sarcoma (KS) may develop because of incompetent immune responses, both nonspecifically and specifically against the KS-associated herpes virus (KSHV). Peripheral blood mononuclear cells from 15 classic (non-AIDS) KS cases, 13 KSHV seropositives (without KS), and 15 KSHV-seronegative controls were tested for interferon-γ T-cell (Elispot) responses to KSHV-LANA, KSHV-K8.1, and CMV/EBV peptide pools. The forearm and thigh of each participant also was tested for delayed-type hypersensitivity (DTH) against common recall antigens. Groups were compared with Fisher exact test and multinomial logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). KSHV Elispot response was detected in 10 (67%) classic KS cases, 11 (85%) KSHV seropositives (without KS), and 2 (13%) seronegative controls. All 4 cases with KSHV-LANA responses had current KS lesions, whereas 5 of 6 cases with KSHV-K8.1 responses had no lesions (P=0.048). No case responded to both LANA and K8.1. Compared to seronegative controls, risk for classic KS was inversely related to DTH in the thigh (OR 0.71, 95% CI 0.55–0.94, P=0.01), directly associated with DTH in the forearm (OR 1.35, 95% CI 1.02–1.80, P=0.04), and tended to be increased 5-fold per KSHV Elispot response (OR 5.13, 95% CI 0.86–30.77, P=0.07). Compared to KSHV seropositives (without KS), risk for classic KS, was reduced 5-fold (OR 0.20, CI 0.03–0.77, P=0.04) per KSHV response. CMV/EBV Elispot responses were irrelevant. Deficiency of both KSHV-specific and –nonspecific immunity is associated with classic KS. This may clarify why Kaposi sarcoma responds to immune reconstitution. PMID:21740480

Are bi-axial proximal sesamoid bone fractures in the British Thoroughbred racehorse a bone fatigue related fracture? A histological study.

PubMed

Kristoffersen, M; Hetzel, U; Parkin, T D H; Singer, E R

2010-01-01

To investigate whether microfractures and alterations in the trabecular bone area are associated with catastrophic bi-axial proximal sesamoid bone fractures (PSBF). Proximal sesamoid bones (PSB) from 10 racehorses with PSBF and from 10 control racehorses without musculoskeletal injury were examined using the bulk basic fuchsin method. Bone histomorphometric and microfracture analysis was performed, and cases and controls compared using two-sample t-test, paired t-test, and Mann-Whitney U test. There was no significant difference in the microfracture density and the trabecular bone area between bones from case and control horses, and between fractured and non-fractured bones in case horses. Microfracture density was low in the areas of the PSB examined. Microfracture density was not significantly different between groups, indicating that propagation of micro-cracks is an unlikely predisposing pathologic alteration in PSBF in British racehorses. There was no significant difference in the bone surface area between groups, which one would expect if modelling, adaptation and an increase in bone density were associated with PSBF fracture in the case horses. Therefore, PSBF in the British racehorse does not appear to be associated with microfractures of the trabecular bone of the PSB. The PSB fractures might represent an acute monotonic fracture; however, the aetiology of the fractures remains unknown with additional research required.

Cumulative exposure to lead and cognition in persons with Parkinson’s disease

PubMed Central

Weuve, Jennifer; Press, Daniel Z.; Grodstein, Francine; Wright, Robert O.; Hu, Howard; Weisskopf, Marc G.

2012-01-01

Background Dementia is an important consequence of Parkinson’s disease (PD), with few known modifiable risk factors. Cumulative exposure to lead, at levels experienced in the community, may exacerbate PD-related neural dysfunction, resulting in impaired cognition. Methods Among 101 persons with PD (“cases”) and, separately, 50 persons without PD (“controls”), we evaluated cumulative lead exposure, gauged via tibia and patella bone lead concentrations, in relation to cognitive function, assessed using a telephone battery developed and validated in a separate sample of PD patients. We also assessed the interaction between lead and case-control status. Results After multivariable adjustment, higher tibia bone lead concentration among PD cases was associated with worse performance on all of the individual telephone tests. In particular, tibia lead levels corresponded to significantly worse performance on a telephone analogue of the Mini-Mental State Examination and tests of working memory and attention. Moreover, higher tibia bone lead concentration was associated with significantly worse global composite score encompassing all the cognitive tests (P=0.04). The magnitude of association per standard deviation increment in tibia bone lead level was equivalent to the difference in global scores among controls in our study who were about seven years apart in age. The tibia lead-cognition association was notably stronger within cases than within controls (Pdifference=0.06). Patella bone lead concentration was not consistently associated with performance on the tests. Conclusions These data provide evidence suggesting that cumulative exposure to lead may result in worsened cognition among persons with PD. PMID:23143985

Prostatitis, other genitourinary infections and prostate cancer: results from a population-based case-control study.

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Schiffmann, Jonas; Sun, Maxine; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2016-03-01

We relied on a population-based case-control study (PROtEuS) to examine a potential association between the presence of histologically confirmed prostate cancer (PCa) and history of genitourinary infections, e.g., prostatitis, urethritis, orchitis and epididymitis. Cases were 1933 men with incident PCa, diagnosed across Montreal hospitals between 2005 and 2009. Population controls were 1994 men from the same residential area and age distribution. In-person interviews collected information about socio-demographic characteristics, lifestyle and medical history, e.g., self-reported history of several genitourinary infections, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. After multivariable adjustment, prostatitis was associated with an increased risk of any PCa (OR 1.81 [1.44-2.27]), but not urethritis (OR 1.05 [0.84-1.30]), orchitis (OR 1.28 [0.92-1.78]) or epididymitis (OR 0.98 [0.57-1.68]). The association between prostatitis and PCa was more pronounced for low-grade PCa (Gleason ≤ 6: OR 2.11 [1.61-2.77]; Gleason ≥ 7: OR 1.59 [1.22-2.07]). Adjusting for frequency of physician visits, PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. Prostatitis was associated with an increased probability for detecting PCa even after adjustment for frequency of PSA testing and physician visits, but not urethritis, orchitis or epididymitis. These considerations may be helpful in clinical risk stratification of individuals in whom the risk of PCa is pertinent.

Case control study of dry eye and related ocular surface abnormalities in Ibadan, Nigeria.

PubMed

Bekibele, C O; Baiyeroju, A M; Ajaiyeoba, A; Akang, E E U; Ajayi, B G K

2010-02-01

Tear instability is associated with symptoms of ocular discomfort and irritation. Many patients with dry eyes remain untreated due to improper diagnoses. To identify symptoms and surface abnormalities associated with dry eyes. One hundred and fifty-six eyes of 78 subjects attending the Eye Clinic of the University College Hospital Ibadan were screened for dry eyes/tear instability using rose Bengal stain (graded 0-9), tear break-up time (TBUT), Schirmer's 1 tests, tear meniscus height and a standardised symptoms questionnaire. Grades 4-9 rose Bengal staining were considered as positive dry eye and were compared with grades 0-3 staining eyes as negative controls. Mean tear meniscus height, Schirmer's test and TBUT were lower among cases than their corresponding control eyes. The difference between the mean Schirmer's test values of cases and their controls were statistically significant (P = 0.00 for right eyes and P = 0.002 for left eyes). Rose Bengal grades were inversely correlated with the mean Schirmer's values (Pearson correlation -0.429, P = 0.05 for right eyes and -0.335, P = 0.03 for left eyes) and TBUT (Pearson correlation -0.316, P = 0.05 for right eyes and -0.212, P = 0.06 for left eyes). About 95.8% of the cases were symptomatic, as opposed to 70.4% of the controls (P = 0.01, Fisher's exact test) and 95.8% of dry right eyes compared to 61.1% of their controls had ocular surface abnormalities (P = 0.001), while 89.5% of dry left eyes compared to 62.7% of controls had surface abnormalities (P = 0.07). A close relationship exists between ocular irritation symptoms, surface abnormalities and functional evidence of tear instability. Such patients should be treated empirically or screened for dry eyes.

Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

PubMed

Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

2016-01-01

The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3). From this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

An outbreak of Salmonella Typhimurium phage type 42 associated with the consumption of raw flour.

PubMed

McCallum, Lisa; Paine, Shevaun; Sexton, Kerry; Dufour, Muriel; Dyet, Kristin; Wilson, Maurice; Campbell, Donald; Bandaranayake, Don; Hope, Virginia

2013-02-01

A cluster of salmonellosis cases caused by Salmonella Typhimurium phage type 42 (STM42) emerged in New Zealand in October 2008. STM42 isolates from a wheat-based poultry feed raw material (broll; i.e., product containing wheat flour and particles of grain) had been identified in the 2 months prior to this cluster. Initial investigations indicated that eating uncooked baking mixture was associated with illness. A case-control study was conducted to test the hypothesis that there was an association between STM42 cases and consumption of raw flour or other baking ingredients. Salmonella isolates from human and non-human sources were compared using pulsed-field gel electrophoresis (PFGE) and multiple-locus variable number tandem repeat analysis (MLVA). Environmental investigations included testing flour and other baking ingredients from case homes, unopened bags of flour purchased from retail stores, and inspection of an implicated flour mill. A case-control study of 39 cases and 66 controls found cases had 4.5 times the odds of consuming uncooked baking mixture as controls (95% confidence interval [CI] 1.6-12.5, p-value 0.001). Examination of individual baking ingredients found that, after adjusting for eggs, flour had an odds ratio (OR) of 5.7 (95% CI 1.1-29.1, p-value 0.035). After adjusting for flour, eggs had an OR of 0.8 (95% CI 0.2-3.4, p-value 0.762). PFGE patterns were identical for all STM42 isolates tested; however, MLVA distinguished isolates that were epidemiologically linked to the cluster. STM42 was recovered from flour taken from four cases' homes, two unopened packs purchased from retail stores and packs from three batches of retrieved (recalled) product. This outbreak was associated with the consumption of uncooked baking mixture containing flour contaminated with STM42. The implicated flour mill initiated a voluntary withdrawal from sale of all batches of flour thought to be contaminated. Media releases informed the public about implicated flour brands and the risks of consuming uncooked baking mixture.

Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada

PubMed Central

Skowronski, Danuta M.; De Serres, Gaston; Crowcroft, Natasha S.; Janjua, Naveed Z.; Boulianne, Nicole; Hottes, Travis S.; Rosella, Laura C.; Dickinson, James A.; Gilca, Rodica; Sethi, Pam; Ouhoummane, Najwa; Willison, Donald J.; Rouleau, Isabelle; Petric, Martin; Fonseca, Kevin; Drews, Steven J.; Rebbapragada, Anuradha; Charest, Hugues; Hamelin, Marie-Ève; Boivin, Guy; Gardy, Jennifer L.; Li, Yan; Kwindt, Trijntje L.; Patrick, David M.; Brunham, Robert C.

2010-01-01

Background In late spring 2009, concern was raised in Canada that prior vaccination with the 2008–09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association. Methods and Findings Studies included: (1) test-negative case-control design based on Canada's sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008–09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33–0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases. Conclusions Prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered. Please see later in the article for the Editors' Summary PMID:20386731

Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

PubMed

Csermely, Gyula; Czeizel, Andrew E; Veszprémi, Béla

2015-02-01

Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA. © 2014 Wiley Periodicals, Inc.

Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer's disease.

PubMed

Morgan, A R; Turic, D; Jehu, L; Hamilton, G; Hollingworth, P; Moskvina, V; Jones, L; Lovestone, S; Brayne, C; Rubinsztein, D C; Lawlor, B; Gill, M; O'Donovan, M C; Owen, M J; Williams, J

2007-09-05

Late-onset Alzheimer's disease (LOAD) is a common neurodegenerative disorder, with a complex etiology. APOE is the only confirmed susceptibility gene for LOAD. Others remain yet to be found. Evidence from linkage studies suggests that a gene (or genes) conferring susceptibility for LOAD resides on chromosome 10. We studied 23 positional/functional candidate genes from our linkage region on chromosome 10 (APBB1IP, ALOX5, AD037, SLC18A3, DKK1, ZWINT, ANK3, UBE2D1, CDC2, SIRT1, JDP1, NET7, SUPV3L1, NEN3, SAR1, SGPL1, SEC24C, CAMK2G, PP3CB, SNCG, CH25H, PLCE1, ANXV111) in the MRC genetic resource for LOAD. These candidates were screened for sequence polymorphisms in a sample of 14 LOAD subjects and detected polymorphisms tested for association with LOAD in a three-stage design involving two stages of genotyping pooled DNA samples followed by a third stage in which markers showing evidence for association in the first stages were subjected to individual genotyping. One hundred and twenty polymorphisms were identified and tested in stage 1 (4 case + 4 control pools totaling 366 case and 366 control individuals). Single nucleotide polymorphisms (SNPs) showing evidence of association with LOAD were then studied in stage 2 (8 case + 4 control pools totaling 1,001 case and 1,001 control individuals). Five SNPs, in four genes, showed evidence for association (P < 0.1) at stage 2 and were individually genotyped in the complete dataset, comprising 1,160 LOAD cases and 1,389 normal controls. Two SNPs in SGPL1 demonstrated marginal evidence of association, with uncorrected P values of 0.042 and 0.056, suggesting that variation in SGPL1 may confer susceptibility to LOAD. Copyright 2007 Wiley-Liss, Inc.

Association Between Genes Involved in Craniofacial Development and Nonsyndromic Cleft Lip and/or Palate in the Brazilian Population.

PubMed

Machado, Renato Assis; Messetti, Ana Camila; de Aquino, Sibele Nascimento; Martelli-Júnior, Hercílio; Swerts, Mário Sérgio Oliveira; de Almeida Reis, Silvia Regina; Moreira, Helenara Salvati Bertolossi; Persuhn, Darlene Camati; Coletta, Ricardo D

2016-09-01

To determine the association of single-nucleotide polymorphisms (SNPs) in genes related to craniofacial development, which were previously identified as susceptibility signals for nonsyndromic oral clefts, in Brazilians with nonsyndromic cleft lip and/or palate (NSCL/P). The SNPs rs748044 (TNP1), rs1106514 (MSX1), rs28372960, rs15251 and rs2569062 (TCOF1), rs7829058 (FGFR1), rs1793949 (COL2A1), rs11653738 (WNT3), and rs242082 (TIMP3) were assessed in a family-based transmission disequilibrium test (TDT) and a structured case-control analysis based on the individual ancestry proportions. The SNPs were initially analyzed by TDT, and polymorphisms showing a trend toward excess transmission were subsequently studied in an independent case-control sample. The study sample consisted of 189 case-parent trios of nonsyndromic cleft lip with or without cleft palate (NSCL±P), 107 case-parent trios of nonsyndromic cleft palate (NSCP), 318 isolated samples of NSCL±P, 189 isolated samples of NSCP, and 599 healthy controls. Association of alleles with NSCL/P pathogenesis. Preferential transmission of SNPs rs28372960 and rs7829058 in NSCL±P trios and rs11653738 in NSCP trios (P = .04) were observed, although the structured case-control analysis did not confirm these associations. The haplotype T-C-C formed by TCOF1 SNPs rs28372960, rs15251, and rs2569062 was more frequently transmitted from healthy parents to NSCL±P offspring, but the P value (P = .01) did not withstand Bonferroni correction for multiple tests. With the modest associations, our results do not support the hypothesis that TNP1, MSX1, TCOF1, FGFR1, COL2A1, WNT3, and TIMP3 variants are risk factors for nonsyndromic oral clefts in the Brazilian population.

Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn disease susceptibility

PubMed Central

Parkes, Miles; Barrett, Jeffrey C; Prescott, Natalie; Tremelling, Mark; Anderson, Carl A; Fisher, Sheila A; Roberts, Roland G; Nimmo, Elaine R; Cummings, Fraser R; Soars, Dianne; Drummond, Hazel; Lees, Charlie W; Khawaja, Saud A; Bagnall, Richard; Burke, Denis A; Todhunter, Catherine E; Ahmad, Tariq; Onnie, Clive M; McArdle, Wendy; Strachan, David; Bethel, Graeme; Bryan, Claire; Deloukas, Panos; Forbes, Alastair; Sanderson, Jeremy; Jewell, Derek P; Satsangi, Jack; Mansfield, John C; Cardon, Lon; Mathew, Christopher G

2008-01-01

A genome-wide association scan in Crohn disease by the Wellcome Trust Case Control Consortium1 detected strong association at 6 novel loci. We tested 37 SNPs from these and other loci for association in an independent case control sample. Replication was obtained for the IRGM gene on chromosome 5q33.1 which induces autophagy (replication P = 6.6 × 10−4, combined P = 2.1 × 10−10), and for 9 other loci including NKX2-3 and gene deserts on chromosomes 1q and 5p13. PMID:17554261

Haplotypic Analysis of Wellcome Trust Case Control Consortium Data

PubMed Central

Browning, Brian L.; Browning, Sharon R.

2008-01-01

We applied a recently developed multilocus association testing method (localized haplotype clustering) to Wellcome Trust Case Control Consortium data (14,000 cases of seven common diseases and 3,000 shared controls genotyped on the Affymetrix 500K array). After rigorous data quality filtering, we identified three disease-associated loci with strong statistical support from localized haplotype cluster tests but with only marginal significance in single marker tests. These loci are chromosomes 10p15.1 with type 1 diabetes (p = 5.1 × 10-9), 12q15 with type 2 diabetes (p = 1.9 × 10-7) and 15q26.2 with hypertension (p = 2.8 × 10-8). We also detected the association of chromosome 9p21.3 with type 2 diabetes (p = 2.8 × 10-8), although this locus did not pass our stringent genotype quality filters. The association of 10p15.1 with type 1 diabetes and 9p21.3 with type 2 diabetes have both been replicated in other studies using independent data sets. Overall, localized haplotype cluster analysis had better success detecting disease associated variants than a previous single-marker analysis of imputed HapMap SNPs. We found that stringent application of quality score thresholds to genotype data substantially reduced false-positive results arising from genotype error. In addition, we demonstrate that it is possible to simultaneously phase 16,000 individuals genotyped on genome-wide data (450K markers) using the Beagle software package. PMID:18224336

A population-based study on the association between chronic periodontitis and sialolithiasis.

PubMed

Hung, Shih-Han; Huang, Hung-Meng; Lee, Hsin-Chien; Ching Lin, Herng; Kao, Li-Ting; Wu, Chuan-Song

2016-04-01

Whereas the impression that poor oral hygiene is linked to the development of sialolithiasis may be widely accepted, very few studies provide evidence to support this. This study therefore aimed to evaluate the association between chronic periodontitis (CP) and the subsequent development of salivary gland stone based on a nationwide coverage database. A case-control study. A total of 987 subjects with sialolithiasis were included as cases. In a ratio of five controls per case, 4,935 controls matched in terms of sex and age group were selected. Conditional logistic regression analysis was performed to determine the possible association of sialolithiasis with previously diagnosed CP. The prevalence of prior CP between cases and controls demonstrated that 1,831 (30.9%) out of the 5,922 sampled subjects had prior CP. By Chi-square test, there was a significant difference in the prevalence of prior CP between the cases and controls (36.8% vs. 29.7%, P < 0.001). By conditional logistic regression analysis, the odds ratio (OR) of prior CP for cases was 1.37 (95% confidence interval [CI], 1.19-1.56) compared to the controls after adjusting for geographic location and tobacco use. Further analyzing the relationship between sialolithiasis and prior CP according to sex, sialolithiasis was associated with prior CP regardless of sex. The adjusted OR of prior CP for the cases was 1.34 (95% CI, 1.10-1.64) and 1.41 (95% CI, 1.15-1.73) for males and females, respectively, when compared to controls. This study demonstrates an association between CP and sialolithiasis. 3b. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer.

PubMed

Rohan, Thomas; Ye, Kenny; Wang, Yihong; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer

PubMed Central

Ye, Kenny; Wang, Yihong; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC. PMID:29432432

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer.

PubMed

Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

2017-03-14

BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.

Evidence of Recessive Alzheimer Disease Loci in a Caribbean Hispanic Data Set

PubMed Central

Ghani, Mahdi; Sato, Christine; Lee, Joseph H.; Reitz, Christiane; Moreno, Danielle; Mayeux, Richard; St George-Hyslop, Peter; Rogaeva, Ekaterina

2014-01-01

IMPORTANCE The search for novel Alzheimer disease (AD) genes or pathologic mutations within known AD loci is ongoing. The development of array technologies has helped to identify rare recessive mutations among long runs of homozygosity (ROHs), in which both parental alleles are identical. Caribbean Hispanics are known to have an elevated risk for AD and tend to have large families with evidence of inbreeding. OBJECTIVE To test the hypothesis that the late-onset AD in a Caribbean Hispanic population might be explained in part by the homozygosity of unknown loci that could harbor recessive AD risk haplotypes or pathologic mutations. DESIGN We used genome-wide array data to identify ROHs (>1 megabase) and conducted global burden and locus-specific ROH analyses. SETTING A whole-genome case-control ROH study. PARTICIPANTS A Caribbean Hispanic data set of 547 unrelated cases (48.8% with familial AD) and 542 controls collected from a population known to have a 3-fold higher risk of AD vs non-Hispanics in the same community. Based on a Structure program analysis, our data set consisted of African Hispanic (207 cases and 192 controls) and European Hispanic (329 cases and 326 controls) participants. EXPOSURE Alzheimer disease risk genes. MAIN OUTCOMES AND MEASURES We calculated the total and mean lengths of the ROHs per sample. Global burden measurements among autosomal chromosomes were investigated in cases vs controls. Pools of overlapping ROH segments (consensus regions) were identified, and the case to control ratio was calculated for each consensus region. We formulated the tested hypothesis before data collection. RESULTS In total, we identified 17 137 autosomal regions with ROHs. The mean length of the ROH per person was significantly greater in cases vs controls (P = .0039), and this association was stronger with familial AD (P = .0005). Among the European Hispanics, a consensus region at the EXOC4 locus was significantly associated with AD even after correction for multiple testing (empirical P value 1 [EMP1], .0001; EMP2, .002; 21 AD cases vs 2 controls). Among the African Hispanic subset, the most significant but nominal association was observed for CTNNA3, a well-known AD gene candidate (EMP1, .002; 10 AD cases vs 0 controls). CONCLUSIONS AND RELEVANCE Our results show that ROHs could significantly contribute to the etiology of AD. Future studies would require the analysis of larger, relatively inbred data sets that might reveal novel recessive AD genes. The next step is to conduct sequencing of top significant loci in a subset of samples with overlapping ROHs. PMID:23978990

The MTHFR C677T polymorphism and risk of acute lymphoblastic leukemia: an updated meta-analysis based on 37 case-control studies.

PubMed

Jiang, Yuan; Hou, Jing; Zhang, Qiang; Jia, Shu-Ting; Wang, Bo-Yuan; Zhang, Ji-Hong; Tang, Wen-Ru; Luo, Ying

2013-01-01

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with acute lymphoblastic leukemia (ALL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for the MTHFRC677T polymorphism and ALL risk. Electronic searches of PubMed and the Chinese Biomedicine database were conducted to select case-control studies containing available genotype frequencies of C677T and the odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of any association. Case-control studies including 6,371 cases and 10,850 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had decreased risk of ALL (OR= 0.776, 95% CI: 0.687~0.877, p< 0.001) in Caucasians (OR= 0.715, 95% CI: 0.655~0.781, p= 0.000). However, results among Asians (OR=0.711, 95% CI: 0.591~1.005, p= 0.055) and others (OR=0.913, 95% CI: 0.656~1.271, p= 0. 590) did not suggest an association. A symmetric funnel plot, the Egger's test (P=0.093), and the Begg- test (P=0.072) were all suggestive of the lack of publication bias. This meta-analysis supports the idea that the MTHFR C677T genotype is associated with risk of ALL in Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between the MTHFRC677T polymorphism and ALL.

No association between SNP rs498055 on chromosome 10 and late-onset Alzheimer disease in multiple datasets.

PubMed

Liang, Xueying; Schnetz-Boutaud, Nathalie; Bartlett, Jackie; Allen, Melissa J; Gwirtsman, Harry; Schmechel, Don E; Carney, Regina M; Gilbert, John R; Pericak-Vance, Margaret A; Haines, Jonathan L

2008-01-01

SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset >or= 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD.

Natural history and clinical detection of undiagnosed coeliac disease in a North American community.

PubMed

Hujoel, I A; Van Dyke, C T; Brantner, T; Larson, J; King, K S; Sharma, A; Murray, J A; Rubio-Tapia, A

2018-05-01

Coeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding. To determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease. This was a case-control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age- and gender-matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing. Of 47 557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight-matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2 years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85-1.63, P = 0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P = 0.005), dermatitis herpetiformis (P = 0.006), chronic fatigue (P = 0.033), thyroiditis (P = 0.003), autoimmune diseases (P = 0.008), and have a family member diagnosed with coeliac disease (P = 0.001). This study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed. © 2018 John Wiley & Sons Ltd and Mayo Foundation.

ERAP1 variants are associated with ankylosing spondylitis in East Asian population: a new Chinese case-control study and meta-analysis of published series.

PubMed

Chen, C; Zhang, X

2015-06-01

Endoplasmic reticulum aminopeptidase 1 (ERAP1) has been confirmed to be associated with ankylosing spondylitis (AS) in Caucasian. However, whether they are associated with AS in East Asian population remains unidentified. We investigated this relationship by a new Chinese case-control study and a meta-analysis of published series. 368 cases and 460 controls were recruited in the Chinese case-control study. Genotyping was completed using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Allelic associations were analysed using contingency tables. In the meta-analysis, up to 2748 cases and 2774 controls from seven different studies and the new Chinese study were combined using Review Manager software version 5.1.1. Mantel-Haenszel or Inverse Variance test was used to calculate fixed or random-effects pooled ORs. In the new Chinese study, strong association with AS was observed for marker rs10050860, rs27434 and rs1065407 at P value of <0.001. Moderate association was observed for rs30187 at P value of <0.01, while no association was observed for rs27044 (P = 0.37) and rs2287987 (P = 0.23). The meta-analysis showed that rs27037 and rs30187 were strongly associated with AS (P < 0.00001). Significant association was also observed for rs27434 (P = 0.001). No association was shown for rs27044 (P = 0.70). We concluded that ERAP1 variants are associated with AS in East Asian population, indicating a common pathogenic mechanism for AS in East Asians and Caucasians. © 2015 John Wiley & Sons Ltd.

Association of α-, β-, and γ-Synuclein With Diffuse Lewy Body Disease

PubMed Central

Nishioka, Kenya; Wider, Christian; Vilariño-Güell, Carles; Soto-Ortolaza, Alexandra I.; Lincoln, Sarah J.; Kachergus, Jennifer M.; Jasinska-Myga, Barbara; Ross, Owen A.; Rajput, Alex; Robinson, Christopher A.; Ferman, Tanis J.; Wszolek, Zbigniew K.; Dickson, Dennis W.; Farrer, Matthew J.

2016-01-01

Objective To determine the association of the genes that encode α-, β-, and γ-synuclein (SNCA, SNCB, and SNCG, respectively) with diffuse Lewy body disease (DLBD). Design Case-control study. Subjects A total of 172 patients with DLBD consistent with a clinical diagnosis of Parkinson disease dementia/dementia with Lewy bodies and 350 clinically and 97 pathologically normal controls. Interventions Sequencing of SNCA, SNCB, and SNCG and genotyping of single-nucleotide polymorphisms performed on an Applied Biosystems capillary sequencer and a Sequenom MassArray pLEX platform, respectively. Associations were determined using χ2 or Fisher exact tests. Results Initial sequencing studies of the coding regions of each gene in 89 patients with DLBD did not detect any pathogenic substitutions. Nevertheless, genotyping of known polymorphic variability in sequence-conserved regions detected several single-nucleotide polymorphisms in the SNCA and SNCG genes that were significantly associated with disease (P=.05 to <.001). Significant association was also observed for 3 single-nucleotide polymorphisms located in SNCB when comparing DLBD cases and pathologically confirmed normal controls (P=.03-.01); however, this association was not significant for the clinical controls alone or the combined clinical and pathological controls (P>.05). After correction for multiple testing, only 1 single-nucleotide polymorphism in SNCG (rs3750823) remained significant in all of the analyses (P=.05-.009). Conclusion These findings suggest that variants in all 3 members of the synuclein gene family, particularly SNCA and SNCG, affect the risk of developing DLBD and warrant further investigation in larger, pathologically defined data sets as well as clinically diagnosed Parkinson disease/dementia with Lewy bodies case-control series. PMID:20697047

Can overt diabetes mellitus be predicted by an early A1C value in gestational diabetics?

PubMed

Granada, Catalina; Forbes, Joanna; Sangi-Haghpeykar, Haleh; Davidson, Christina

2014-01-01

To test the hypothesis that a hemoglobin A1C value (A1C) in early pregnancy is predictive of overt diabetes mellitus (DM) postpartum in women with gestational diabetes (GDM). In this case-control analysis of women with an early pregnancy diagnosis of GDM, we estimated the association between an early pregnancy A1C and subsequent diagnosis of DM. Women with a normal postpartum diabetic screen (controls) were compared against those with confirmed postpartum DM (cases). Ability of A1C levels to predict DM was examined via logistic regression analysis and corresponding receiver operating characteristic values. During the 10-year study period 166 women met the inclusion criteria: 140 (84%) had normal postpartum testing (controls), and 26 (16%) were diagnosed with DM (cases). The mean A1C value was significantly higher among cases than controls (6.7 vs. 5.6, p < 0.0001, SD 1.3-5). Cases had A1Cs ranging from 5.5- 11.7%, while controls had A1Cs ranging from 4.3-7.8%. The best discriminatory cut point for postpartum DM was an A1C > 5.9% (sensitivity 81%, specificity 83%, positive predictive value 47%, negative predictive value Our findings suggest that an elevated early pregnancy A1C may be predictive of overt DM. Larger studies are needed to further validate this association.

An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda

PubMed Central

Foltz, Jennifer L.; Makumbi, Issa; Sejvar, James J.; Malimbo, Mugagga; Ndyomugyenyi, Richard; Atai-Omoruto, Anne Deborah; Alexander, Lorraine N.; Abang, Betty; Melstrom, Paul; Kakooza, Angelina M.; Olara, Dennis; Downing, Robert G.; Nutman, Thomas B.; Dowell, Scott F.; Lwamafa, D. K. W.

2013-01-01

Introduction Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda. Methods In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations. Results Surveillance identified 224 cases; most (95%) were 5–15-years-old (range = 2–27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6–46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1) = 14·4 (2·7, 78·3)], exposure to munitions [AOR1 = 13·9 (1·4, 135·3)], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%). Conclusion NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies. PMID:23823012

Orbital fractures due to domestic violence: an epidemiologic study.

PubMed

Goldberg, Stuart H.; McRill, Connie M.; Bruno, Christopher R.; Ten Have, Tom; Lehman, Erik

2000-09-01

Domestic violence is an important cause of orbital fractures in women. Physicians who treat patients with orbital fractures may not suspect this mechanism of injury. The purpose of this study was to assess the association between domestic violence and orbital fractures. A medical center-based case-control study with matching on age and site of admission was done. Medical center databases were searched using ICD-9 codes to identify all cases of orbital fractures encountered during a three-year period. Medical records of female patients age 13 and older were reviewed along with those of age, gender and site of admission matched controls. A stratified exact test was employed to test the association between domestic violence and orbital fracture. Among 41 adult female cases with orbital fractures treated at our medical center, three (7.3%) reported domestic violence compared to zero among the matched controls (p = 0.037). We believe that domestic violence may be under-reported in both orbital fracture cases and controls. This may result in an underestimate of the orbital fracture versus domestic violence association. Domestic violence is a serious women's health and societal problem. Domestic violence may have a variety of presentations, including illnesses and injuries. Orbital fracture is an identifiable manifestation of domestic violence. Domestic violence is more likely to be detected in adult female hospital patients with orbital fracture than in matched controls with any other diagnosis. Physicians who treat patients with orbital fractures should be familiar with this mechanism of injury.

Is there an association between temporomandibular disorders and playing a musical instrument? A review of literature.

PubMed

Attallah, M M; Visscher, C M; van Selms, M K A; Lobbezoo, F

2014-07-01

Temporomandibular disorders (TMDs) have a multifactorial etiology. Among others, parafunctions and oral habits have been suggested as important initiating and perpetuating factors. Playing a musical instrument that loads the masticatory system, like wind instruments and the violin or viola, has been suggested to be part of this group of etiological factors. However, the evidence base for this suggestion is lacking. Therefore, the aim of this study was to review the literature on the possible association between playing a musical instrument and developing and/or having a TMD. A PubMed search, using the query ['Music'(Mesh) AND 'Craniomandibular Disorders'(Mesh)], yielded 19 articles, 14 of which were included in this review. Six of 14 papers had a case-control or pre-test-post-test design; the remaining eight papers were case reports of expert opinions. The former papers were analysed and tabulated according to the PICO (Patient/population-Intervention-Control/comparison-Outcome/results) system; the latter ones were only summarised and tabulated. All articles with a case-control or pre-test-post-test design suggested a possible association between TMD and playing a musical instrument, especially the violin and viola. However, no clear-cut conclusion could be drawn as to whether playing a musical instrument is directly associated with TMD, or only in combination with other factors. More and better research on this topic is needed, as to enable a better counselling and possibly even a better treatment of the suffering musician. © 2014 John Wiley & Sons Ltd.

CARD15 Gene Polymorphisms Are Associated with Tuberculosis Susceptibility in Chinese Holstein Cows

PubMed Central

Liu, Tong; Tu, Wenji; Li, Wengui; Dong, Guodong; Xu, Cong; Qin, Bo; Liu, Kaihua; Yang, Jie; Chai, Jun; Shi, Xianwei; Zhang, Yifang

2015-01-01

Bovine tuberculosis (BTB) is a significant veterinary and financial problem in many parts of the world. Associations between specific host genes and susceptibility to mycobacterial infections, such as tuberculosis, have been reported in several species. The objective of this study was to identify and evaluate the relationship of single-nucleotide polymorphisms (SNPs) in the CARD15 gene with susceptibility to BTB in Chinese Holstein cows. DNA samples from 201 Chinese Holstein cows (103 cases and 98 controls) were collected from Kunming City, Yuxi City, and Dali City in China. SNPs in the CARD15 gene were assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Case-control association testing and statistical analysis identified six SNPs associated with susceptibility to BTB in Chinese Holstein cows. The frequency of genotypes C/T, A/G, A/G, A/G, C/T, and A/G in E4 (-37), 208, 1644, 1648, 1799, and E10 (+107), respectively, was significantly higher in cases than in controls, and also the alleles C, A, A, G, T, and A, respectively, were associated with a greater relative risk in cases than in controls. The distribution of two haplotypes, TGGACA and CAGACA, was significantly different between cases and controls. Overall, this case-control study suggested that E4 (-37)(C/T), 208(A/G), 1644(A/G), 1648(A/G), 1799(C/T), and E10 (+107)(A/G) in the CARD15 gene were significantly associated with susceptibility to BTB in Chinese Holstein cows and that haplotypes TGGACA and CAGACA could be used as genetic markers in marker-assisted breeding programs for breeding cows with high resistance to BTB. PMID:26244859

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012

PubMed Central

McKerr, Caoimhe; Adak, Goutam K.; Nichols, Gordon; Gorton, Russell; Chalmers, Rachel M.; Kafatos, George; Cosford, Paul; Charlett, Andre; Reacher, Mark; Pollock, Kevin G.; Alexander, Claire L.; Morton, Stephen

2015-01-01

Background We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. Methods Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. Results Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle. PMID:26017538

Myelogenous leukemia and electric blanket use.

PubMed

Preston-Martin, S; Peters, J M; Yu, M C; Garabrant, D H; Bowman, J D

1988-01-01

In a case-control study of adult acute and chronic myelogenous leukemia in Los Angeles County, we tested the hypothesis that excess exposure to electromagnetic fields from electric blankets was associated with risk of leukemia. We did this by studying 116 cases of acute myelogenous leukemia (AML) and 108 cases of chronic myelogenous leukemia (CML) along with matched neighborhood controls. The cases and controls were queried as to electric blanket use and the risks computed. For AML the risk was 0.9 (95% CI 0.5-1.6) and for CML the risk was 0.8 (95% CI 0.4-1.6). Cases did not differ from controls by duration of use, year of first regular use, year since last use, or socioeconomic status. Our best estimates of exposure indicate that electric blanket use increases overall exposure to electric fields by less than 50% and magnetic fields by less than 100%. We conclude that there is no major leukemogenic risk associated with electric blanket use in Los Angeles County.

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012.

PubMed

McKerr, Caoimhe; Adak, Goutam K; Nichols, Gordon; Gorton, Russell; Chalmers, Rachel M; Kafatos, George; Cosford, Paul; Charlett, Andre; Reacher, Mark; Pollock, Kevin G; Alexander, Claire L; Morton, Stephen

2015-01-01

We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle.

Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis

PubMed Central

Davoudi, Samaneh; Chang, Victoria S.; Navarro-Gomez, Daniel; Stanwyck, Lynn K.; Sevgi, Damla Duriye; Papavasileiou, Evangelia; Ren, Aiai; Uchiyama, Eduardo; Sullivan, Lynn; Lobo, Ann-Marie; Papaliodis, George N.

2018-01-01

Purpose Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk. PMID:29416296

The Daniel K. Inouye College of Pharmacy Scripts: Updates on Clostridium difficile Infection: Advances in Laboratory Testing to Aid Diagnosis and Treatment.

PubMed

Lteif, Louis

2017-02-01

Clostridium difficile remains a major source of nosocomial infections and associated diarrhea. More recently, community-acquired cases are on the rise creating a concern for a serious public health threat. Appropriate infection control precautions as well as prevention and optimal management may help to avoid detrimental outbreaks. A key step is utilizing laboratory testing for quick and accurate diagnosis of potential cases. This overview article describes Clostridium difficile infection control and prevention methods and updates the most recent management strategies including a focus on the utilization and interpretation of laboratory diagnostic testing and appropriate treatment.

Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence.

PubMed

Liu, Gang; Mukherjee, Bhramar; Lee, Seunggeun; Lee, Alice W; Wu, Anna H; Bandera, Elisa V; Jensen, Allan; Rossing, Mary Anne; Moysich, Kirsten B; Chang-Claude, Jenny; Doherty, Jennifer A; Gentry-Maharaj, Aleksandra; Kiemeney, Lambertus; Gayther, Simon A; Modugno, Francesmary; Massuger, Leon; Goode, Ellen L; Fridley, Brooke L; Terry, Kathryn L; Cramer, Daniel W; Ramus, Susan J; Anton-Culver, Hoda; Ziogas, Argyrios; Tyrer, Jonathan P; Schildkraut, Joellen M; Kjaer, Susanne K; Webb, Penelope M; Ness, Roberta B; Menon, Usha; Berchuck, Andrew; Pharoah, Paul D; Risch, Harvey; Pearce, Celeste Leigh

2018-02-01

There have been recent proposals advocating the use of additive gene-environment interaction instead of the widely used multiplicative scale, as a more relevant public health measure. Using gene-environment independence enhances statistical power for testing multiplicative interaction in case-control studies. However, under departure from this assumption, substantial bias in the estimates and inflated type I error in the corresponding tests can occur. In this paper, we extend the empirical Bayes (EB) approach previously developed for multiplicative interaction, which trades off between bias and efficiency in a data-adaptive way, to the additive scale. An EB estimator of the relative excess risk due to interaction is derived, and the corresponding Wald test is proposed with a general regression setting under a retrospective likelihood framework. We study the impact of gene-environment association on the resultant test with case-control data. Our simulation studies suggest that the EB approach uses the gene-environment independence assumption in a data-adaptive way and provides a gain in power compared with the standard logistic regression analysis and better control of type I error when compared with the analysis assuming gene-environment independence. We illustrate the methods with data from the Ovarian Cancer Association Consortium. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An agent-based model evaluation of economic control strategies for paratuberculosis in a dairy herd.

PubMed

Verteramo Chiu, Leslie J; Tauer, Loren W; Al-Mamun, Mohammad A; Kaniyamattam, Karun; Smith, Rebecca L; Grohn, Yrjo T

2018-04-25

This paper uses an agent-based simulation model to estimate the costs associated with Mycobacterium avium ssp. paratuberculosis (MAP), or Johne's disease, in a milking herd, and to determine the net benefits of implementing various control strategies. The net present value (NPV) of a 1,000-cow milking herd is calculated over 20 yr, parametrized to a representative US commercial herd. The revenues of the herd are generated from sales of milk and culled animals. The costs include all variable and fixed costs necessary to operate a representative 1,000-cow milking herd. We estimate the NPV of the herd with no MAP infection, under an expected endemic infection distribution with no controls, and under an expected endemic infection distribution with various controls. The initial number of cows in a herd with an endemic MAP infection is distributed as 75% susceptible, 13% latent, 9% low MAP shedding, and 3% high MAP shedding. Control strategies include testing using ELISA and fecal culture tests and culling of cows that test positive, and culling based on observable milk production decrease. Results show that culling cows based on test results does not increase the herd's NPV and in most cases decreases NPV due to test costs as well as false positives and negatives with their associated costs (e.g., culling healthy cows and keeping infected cows). Culling consistently low producing cows when MAP is believed to be present in the herd produces higher NPV over the strategy of testing and culling MAP infected animals, and over the case of no MAP control. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Attention in selective mutism--an exploratory case-control study.

PubMed

Oerbeck, Beate; Kristensen, Hanne

2008-01-01

The aim of the study was to explore the association between selective mutism (SM) and attention. In SM social anxiety seems central but language impairment and motor problems are also reported. Attention problems have been described in parental behavioral ratings, while neuropsychological studies are lacking. A neuropsychological test (the Trail Making Test) and parental ratings of attention- and anxiety problems were administered to a clinical sample of 23 children with SM (aged 7-16 years, 12 boys and 11 girls) and 46 non-referred matched controls. The SM group differed from controls on the Trail Making Test, but the group difference disappeared, when controlling for motor function and IQ. Parental ratings of attention problems were not significantly associated with the neuropsychological attention measure. Neuropsychological studies of attention controlled for IQ and motor function are needed as well as tests that measure different aspects of attention.

Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A Matched Case-Control Study in a Mexican Population.

PubMed

Alvarado-Esquivel, Cosme; Loera-Moncivais, Nayely; Hernandez-Tinoco, Jesus; Sanchez-Anguiano, Luis Francisco; Hernandez-Madrid, Guillermina; Rabago-Sanchez, Elizabeth; Centeno-Tinoco, Maria Magdalena; Sandoval-Carrillo, Ada A; Salas-Pacheco, Jose M; Campos-Moreno, Oscar Vladimir; Antuna-Salcido, Elizabeth Irasema

2017-06-01

Very little is known about the association between infection with Toxoplasma gondii ( T. gondii ) and diabetes mellitus. We perform an age- and gender-matched case-control study to determine the association of T. gondii infection and diabetes mellitus. Cases included 156 patients with diabetes mellitus and 156 controls without diabetes mellitus who attended in two public clinics in Durango City, Mexico. Sera of cases and controls were tested for the presence of anti- Toxoplasma IgG and IgM antibodies using commercially available enzyme-linked fluorescence assays (ELFA). Anti- T. gondii IgG antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156 controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P = 0.18). The frequency of high (> 150 IU/mL) anti- T. gondii IgG levels in seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10 cases and five controls with seropositivity to anti- T. gondii IgG antibodies were positive for anti- T. gondii IgM antibodies. Stratification by gender showed similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 - 31.19; P = 0.61). We conclude that there is not serological evidence of an association between T. gondii infection and diabetes mellitus in the studied subjects in Durango City, Mexico. Further studies to elucidate the role of T. gondii in diabetes should be conducted.

Lack of Association Between Toxoplasma gondii Infection and Diabetes Mellitus: A Matched Case-Control Study in a Mexican Population

PubMed Central

Alvarado-Esquivel, Cosme; Loera-Moncivais, Nayely; Hernandez-Tinoco, Jesus; Sanchez-Anguiano, Luis Francisco; Hernandez-Madrid, Guillermina; Rabago-Sanchez, Elizabeth; Centeno-Tinoco, Maria Magdalena; Sandoval-Carrillo, Ada A.; Salas-Pacheco, Jose M.; Campos-Moreno, Oscar Vladimir; Antuna-Salcido, Elizabeth Irasema

2017-01-01

Background Very little is known about the association between infection with Toxoplasma gondii (T. gondii) and diabetes mellitus. We perform an age- and gender-matched case-control study to determine the association of T. gondii infection and diabetes mellitus. Methods Cases included 156 patients with diabetes mellitus and 156 controls without diabetes mellitus who attended in two public clinics in Durango City, Mexico. Sera of cases and controls were tested for the presence of anti-Toxoplasma IgG and IgM antibodies using commercially available enzyme-linked fluorescence assays (ELFA). Results Anti-T. gondii IgG antibodies were found in 10 (6.4%) of the 156 cases and in five (3.2%) of the 156 controls (odds ratio (OR): 2.06; 95% confidence interval (CI): 0.69 - 6.19; P = 0.18). The frequency of high (> 150 IU/mL) anti-T. gondii IgG levels in seropositive cases (1/10: 10.0%) was comparable to the one (1/5: 20%) in seropositive controls (OR: 0.44; 95% CI: 0.02 - 9.03; P = 1.00). None of the 10 cases and five controls with seropositivity to anti-T. gondii IgG antibodies were positive for anti-T. gondii IgM antibodies. Stratification by gender showed similar frequencies of T. gondii infection in female cases (7/107: 6.5%) and female controls (4/107: 3.7%) (OR: 1.80; 95% CI: 0.51 - 6.34; P = 0.53), and in male cases (3/49: 6.1%) and male controls (1/49: 2.0%) (OR: 3.13; 95% CI: 0.31 - 31.19; P = 0.61). Conclusions We conclude that there is not serological evidence of an association between T. gondii infection and diabetes mellitus in the studied subjects in Durango City, Mexico. Further studies to elucidate the role of T. gondii in diabetes should be conducted. PMID:28496551

Detection of Acute and Long-Term Effects of Concussion: Dual-Task Gait Balance Control Versus Computerized Neurocognitive Test.

PubMed

Howell, David R; Osternig, Louis R; Chou, Li-Shan

2018-02-16

To examine the acute (within 72h of injury) and long-term (2mo postinjury) independent associations between objective dual-task gait balance and neurocognitive measurements among adolescents and young adults with a concussion and matched controls. Longitudinal case-control. Motion analysis laboratory. A total of 95 participants completed the study: 51 who sustained a concussion (mean age, 17.5±3.3y; 71% men) and 44 controls (mean age, 17.7±2.9y; 72% men). Participants who sustained a concussion underwent a dual-task gait analysis and computerized neurocognitive testing within 72 hours of injury and again 2 months later. Uninjured controls also completed the same test protocol in similar time increments. Not applicable. We compared dual-task gait balance control and computerized neurocognitive test performance between groups using independent samples t tests. Multivariable binary logistic regression models were then constructed for each testing time to determine the association between group membership (concussion vs control), dual-task gait balance control, and neurocognitive function. Medial-lateral center-of-mass displacement during dual-task gait was independently associated with group membership at the initial test (adjusted odds ratio [aOR], 2.432; 95% confidence interval [CI], 1.269-4.661) and 2-month follow-up test (aOR, 1.817; 95% CI, 1.014-3.256) tests. Visual memory composite scores were significantly associated with group membership at the initial hour postinjury time point (aOR, .953; 95% CI, .833-.998). However, the combination of computerized neurocognitive test variables did not predict dual-task gait balance control for participants with concussion, and no single neurocognitive variable was associated with dual-task gait balance control at either testing time. Dual-task assessments concurrently evaluating gait and cognitive performance may allow for the detection of persistent deficits beyond those detected by computerized neurocognitive deficits alone. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Misconceptions about HIV infection in Kinshasa (Democratic Republic of Congo): a case-control study on knowledge, attitudes and practices.

PubMed

Carlos, Silvia; Martínez-González, Miguel Ángel; Burgueño, Eduardo; López-Del Burgo, Cristina; Ruíz-Canela, Miguel; Ndarabu, Adolphe; Tshilolo, Léon; Tshiswaka, Philomène; Labarga, Pablo; de Irala, Jokin

2015-08-01

To evaluate the prevalence of HIV-related misconceptions in an outpatient centre of Kinshasa (Democratic Republic of Congo) and analyse the association between these beliefs and HIV infection. A case-control study was carried out from December 2010 until June 2012. We assessed 1630 participants aged 15-49 attending a primary outpatient centre in Kinshasa: 762 HIV Voluntary Counselling and Testing attendees and 868 blood donors. A 59-item questionnaire about knowledge, attitudes and practice was administered during a face-to-face interview, followed by an HIV test. Cases and controls were respondents with a newly diagnosed HIV-positive or HIV-negative test, respectively. Unconditional logistic regression was used to analyse the association between misconceptions and HIV seropositivity. 274 cases and 1340 controls were recruited. Cases were more likely than controls to have a low socioeconomic status, no education, to be divorced/separated or widowed. An association was found between the following variables and HIV seropositivity: having a poor HIV knowledge (adjusted OR=2.79; 95% CI 1.43 to 5.45), not knowing a virus is the cause of AIDS (adjusted OR=2.03; 95% CI 1.38 to 2.98) and reporting more than three HIV-transmission-related misconceptions (adjusted OR=3.30; 95% CI 1.64 to 6.64), such as thinking an HIV-positive person cannot look healthy and that HIV is transmitted by sorcery, God's punishment, a kiss on the mouth, mosquitoes, coughs/sneezes or undercooked food. Despite having access to healthcare services, there are still many people in Kinshasa that have HIV-related misconceptions that increase their HIV risk. Our findings underscore the need for a culturally adapted and gender-orientated basic HIV information into Congolese HIV prevention programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Risk factors for oropharyngeal gonorrhoea in men who have sex with men: an age-matched case-control study.

PubMed

Cornelisse, Vincent J; Walker, Sandra; Phillips, Tiffany; Hocking, Jane S; Bradshaw, Catriona S; Lewis, David A; Prestage, Garrett Paul; Grulich, Andrew E; Fairley, Christopher K; Chow, Eric P F

2018-01-22

Oropharyngeal gonorrhoea is common among men who have sex with men (MSM). We aimed to clarify which oral sex practices were independent risk factors for oropharyngeal gonorrhoea: tongue kissing, receptive oro-penile sex (fellatio) or insertive oro-anal sex (rimming), and whether daily use of mouthwash and recent antibiotic use was protective. In 2015, we conducted an age-matched case-control study of MSM who attended the Melbourne Sexual Health Centre. Cases had tested positive for oropharyngeal gonorrhoea by nucleic acid amplification testing, and controls had tested negative. Questionnaire items included tongue kissing, oral sex practices, condom use, recent antibiotic use, mouthwash use and alcohol consumption. We identified 177 cases, age matched to 354 controls. In univariable analyses, cases were 1.90 times (95% CI 1.13 to 3.20) more likely than controls to have had casual sexual partners (CSP) in the preceding 3 months, were 2.17 times (95% CI 1.31 to 3.59) more likely to have kissed CSP and were 2.04 times (95% CI 1.26 to 3.30) more likely to have had receptive oro-penile sex with CSP. Oropharyngeal gonorrhoea was not associated with insertive oro-anal sex or mouthwash use. The number of CSP for tongue kissing and receptive oral sex and total CSP were highly correlated, and in multivariable analysis neither kissing nor receptive oro-penile sex was significantly associated with having oropharyngeal gonorrhoea, after adjusting for total number of CSP. The finding that oropharyngeal gonorrhoea was associated with a higher number of sexual partners but not specific sexual practices highlights the need for further research in the area of gonorrhoea transmission to define the probability of transmission from specific sex acts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case-Control Data?

PubMed

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case-control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case-control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case-control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls.

The association between reflux esophagitis and airway hyper-reactivity in patients with gastro-esophageal reflux.

PubMed

Karbasi, Ashraf; Ardestani, Mohammad Emami; Ghanei, Mostafa; Harandi, Ali Amini

2013-06-01

The association of gastro-esophageal reflux (GER) with a wide variety of pulmonary disorders was recognized. We aimed to evaluate the effect of GER-induced esophagitis on airway hyper-reactivity (AHR) in patients and the response to treatment. In this cohort study, 30 patients attending the gastrointestinal clinic of a university hospital with acid reflux symptoms were included. All patients were evaluated endoscopically and divided into case group with esophagitis and control group without any evidence of esophagitis. Spirometry and methacholine test were done in all patients before and after treatment of GER with pantoprazole 40 mg daily for six months. There was a significant difference in the rate of positive methacholine test between the cases (40%) and the controls (6.7%) prior to anti-acid therapy (P < 0.0001). After six months of treatment, the frequency of positive methacholine test diminished from 40 to 13.3% in the case group (P < 0.05) but did not change in the controls (P = 0.15). The presence of esophagitis due to GER would increase the AHR and treatment with pantoperazole would decrease AHR in patients with proved esophagitis and no previous history of asthma after six months.

Genotyping and inflated type I error rate in genome-wide association case/control studies

PubMed Central

Sampson, Joshua N; Zhao, Hongyu

2009-01-01

Background One common goal of a case/control genome wide association study (GWAS) is to find SNPs associated with a disease. Traditionally, the first step in such studies is to assign a genotype to each SNP in each subject, based on a statistic summarizing fluorescence measurements. When the distributions of the summary statistics are not well separated by genotype, the act of genotype assignment can lead to more potential problems than acknowledged by the literature. Results Specifically, we show that the proportions of each called genotype need not equal the true proportions in the population, even as the number of subjects grows infinitely large. The called genotypes for two subjects need not be independent, even when their true genotypes are independent. Consequently, p-values from tests of association can be anti-conservative, even when the distributions of the summary statistic for the cases and controls are identical. To address these problems, we propose two new tests designed to reduce the inflation in the type I error rate caused by these problems. The first algorithm, logiCALL, measures call quality by fully exploring the likelihood profile of intensity measurements, and the second algorithm avoids genotyping by using a likelihood ratio statistic. Conclusion Genotyping can introduce avoidable false positives in GWAS. PMID:19236714

The utility of the Kohlman Evaluation of Living Skills test is associated with substantiated cases of elder self-neglect.

PubMed

Pickens, Sabrina; Naik, Aanand D; Burnett, Jason; Kelly, P A; Gleason, Mary; Dyer, Carmel B

2007-03-01

Self-neglect is the most prevalent finding among cases reported to Adult Protective Services (APS) and is characterized by an inability to meet one's own basic needs. The Kohlman evaluation of living skills (KELS) has been validated in geriatric populations to assess performance with both instrumental and basic activities of daily living and as an assessment tool for the capacity to live independently; therefore, the purpose of this analysis was to compare the scores of the KELS between substantiated cases of self-neglect and matched community-dwelling elders. This is a cross-sectional pilot study of 50 adults aged 65 years and older who were recruited from APS as documented cases of self-neglect and 50 control participants recruited from Harris County Hospital District outpatient clinics. Control participants were matched for age, race, gender, and ZIP code. A geriatric nurse practitioner (NP)-led team administered a comprehensive geriatric assessment in homes of all study participants. The assessment included the KELS and mini-mental state examination (MMSE) tests. Chi-square analyses were used to determine if cases of self-neglect were significantly more likely to fail the KELS test than matched controls. The analyses revealed that self-neglectors were significantly more likely to fail the KELS than non-self-neglectors (50% vs. 30%, p = .025). When stratified by MMSE scores, self-neglectors with intact cognitive function remained significantly more likely to fail the KELS compared to matched, cognitively intact controls (45% vs. 17%, p = .013). Abnormal results using an in-home KELS test were significantly associated with substantiated cases of self-neglect. There is currently no gold-standard measure for identifying capacity with self-care behaviors among cases of self-neglect. As a result, self-neglect may remain unidentified in many clinical settings. The KELS provides clinicians with an objective measure of an individual's capacity and performance with everyday life-supporting tasks and thus, provides information that can help NPs identify elders at risk for self-neglect. These findings suggest that the KELS test has significant utility as part of a comprehensive geriatric assessment to aid clinicians in suspected cases of self-neglect.

Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer

PubMed Central

Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven

2017-01-01

Background: BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. Methods: A larger multi-centre, case–control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ2- and Fisher's exact test, and median DFS/OS using Kaplan–Meier method and log-rank testing. Results: Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34–78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). Conclusions: In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation. PMID:28183138

Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

PubMed Central

Liu, Li; Sabo, Aniko; Neale, Benjamin M.; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; DePristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Makarov, Vladimir; Maguire, Jared; Newsham, Irene; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Wu, Yuanqing; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Devlin, Bernie; Schellenberg, Gerard D.; Sutcliffe, James S.; Daly, Mark J.; Gibbs, Richard A.; Roeder, Kathryn

2013-01-01

We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. PMID:23593035

Factors associated with unreported tuberculosis cases in Spanish hospitals.

PubMed

Morales-García, Concepción; Rodrigo, Teresa; García-Clemente, Marta M; Muñoz, Ana; Bermúdez, Pilar; Casas, Francisco; Somoza, María; Milá, Celia; Penas, Antón; Hidalgo, Carmen; Casals, Martí; Caylá, Joan A

2015-07-29

Under-reporting of tuberculosis (TB) cases complicates disease control, hinders contact tracing and alters the accuracy of epidemiological data, including disease burden. The objective of the present study is to evaluate the proportion of unreported TB cases in Spanish healthcare facilities and to identify the associated factors. A multi-center retrospective study design was employed. The study included TB cases diagnosed in 16 facilities during 2011-2012. These cases were compared to those reported to the corresponding public health departments. Demographic, microbiological and clinical data were analyzed to determine the factors associated with unreported cases. Associated factors were analyzed on a bivariate level using the x(2) test and on a multivariate level using a logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated. Of the 592 TB cases included in the study, 85 (14.4 %) were not reported. The percentage of unreported cases per healthcare center ranged from 0-45.2 %. The following variables were associated to under-reporting at a multivariate level: smear-negative TB (OR = 1.87; CI:1.07-3.28), extrapulmonary disease (OR = 2.07; CI:1.05-4.09) and retired patients (OR = 3.04; CI:1.29-7.18). A nurse case manager was present in all of the centers with 100 % reporting. The percentage of reported cases among the smear-positive cases was 9.4 % and 19.4 % (p = 0.001) among the rest of the study population. Smear-positive TB was no associated to under-reporting. It is important that TB Control Programs encourage thorough case reporting to improve disease control, contact tracing and accuracy of epidemiological data. The help from a TB nurse case manager could improve the rate of under-reporting.

Effectiveness of influenza vaccine against life-threatening RT-PCR-confirmed influenza illness in US children, 2010-2012.

PubMed

Ferdinands, Jill M; Olsho, Lauren E W; Agan, Anna A; Bhat, Niranjan; Sullivan, Ryan M; Hall, Mark; Mourani, Peter M; Thompson, Mark; Randolph, Adrienne G

2014-09-01

No studies have examined the effectiveness of influenza vaccine against intensive care unit (ICU) admission associated with influenza virus infection among children. In 2010-2011 and 2011-2012, children aged 6 months to 17 years admitted to 21 US pediatric intensive care units (PICUs) with acute severe respiratory illness and testing positive for influenza were enrolled as cases; children who tested negative were PICU controls. Community controls were children without an influenza-related hospitalization, matched to cases by comorbidities and geographic region. Vaccine effectiveness was estimated with logistic regression models. We analyzed data from 44 cases, 172 PICU controls, and 93 community controls. Eighteen percent of cases, 31% of PICU controls, and 51% of community controls were fully vaccinated. Compared to unvaccinated children, children who were fully vaccinated were 74% (95% CI, 19% to 91%) or 82% (95% CI, 23% to 96%) less likely to be admitted to a PICU for influenza compared to PICU controls or community controls, respectively. Receipt of 1 dose of vaccine among children for whom 2 doses were recommended was not protective. During the 2010-2011 and 2011-2012 US influenza seasons, influenza vaccination was associated with a three-quarters reduction in the risk of life-threatening influenza illness in children. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study

PubMed Central

Moncayo, A-L; Vaca, M; Oviedo, G; Workman, L J; Chico, M E; Platts-Mills, T A E; Rodrigues, L C; Barreto, M L; Cooper, P J

2013-01-01

Background Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. Objective To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. Methods A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. Results The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. Conclusions and clinical relevance Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation. PMID:23278881

Modifiable factors associated with active pulmonary tuberculosis in a Kenyan prison.

PubMed

Amwayi, A S; Kikuvi, G M; Muchiri, E M

2010-02-01

To establish modifiable factors associated with active pulmonary tuberculosis (PTB) among prisoners. Retrospective matched case-control study. Nakuru GK prison in Kenya. A total of 144 subjects (48 cases and 96 controls) were recruited into the study. Cases were adult prisoners who had at least two initial sputum specimens being Acid Fast Bacilli-positive (AFB+) on direct smear microscopy and hence recruited to PTB WHO DOTS Programme. Controls were adults with no chronic cough and not on PTB treatment six months prior to the study. Independent factors significantly associated with active PTB disease were: self reported HIV+ status (OR=11; 95% CI = 2.42-47.77), evidence of BCG vaccination (OR = 0.20; 95% CI = 0.05-0.60), contact with PTB case (OR = 7.0; 95% CI = 1.17-38.23), unemployment (OR = 9.0; 95% CI = 1.84-43.97) and sharing linen (OR = 4.32; 95%CI = 1.08-17.29). Modifiable factors associated with active PTB in Nakuru G.K prison are: HIV status, BCG vaccination, PTB case contact, poverty and poor personal hygiene. We recommend HIV counselling and testing of all PTB patients, screening for TB upon prison entry and TB contact investigation and improving personal hygiene of prisoners.

Maternal hypertension, medication use, and hypospadias in the National Birth Defects Prevention Study.

PubMed

Van Zutphen, Alissa R; Werler, Martha M; Browne, Marilyn M; Romitti, Paul A; Bell, Erin M; McNutt, Louise-Anne; Druschel, Charlotte M; Mitchell, Allen A

2014-02-01

To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study. Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997-2009 births in a population-based case-control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing. Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective β-blockers, centrally acting agents, renin-angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective β-blockers (adjusted OR 3.22, 95% CI 1.47-7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76-2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41-6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective β-blocker use, and late initiation of treatment, respectively. Our study suggests a relationship between hypospadias and the severity of hypertension. II.

Case-control study of hydrocarbon exposures in patients with renal cell carcinoma.

PubMed Central

Sharpe, C R; Rochon, J E; Adam, J M; Suissa, S

1989-01-01

A retrospective case-control study tested the hypothesis that exposure to hydrocarbon combustion products is associated with the development of renal cell carcinoma. One control per case, matched for sex, date of birth (within 5 years) and urologist, was chosen. Controls were patients who presented with hematuria and were shown not to have a urinary tract tumour. A total of 164 cases and 161 controls responded to mailed questionnaires and telephone interviews. Smoking more than 20 cigarettes per day was associated with the presence of metastatic renal cell carcinoma (p less than 0.001). Exposure to burning coal was associated with an increased relative risk of the disease but only when the exposure occurred between the ages of 10 and 24 years (p less than 0.05). Dose-response relations were demonstrated for intensity of exposure (p less than 0.025) and duration of occupational exposure (p less than 0.05). The distribution of latent periods from first exposure to diagnosis was bimodal, with one mode at 21 to 30 years and another at 41 to 50 years. Occupational exposure to tar or pitch or both was also associated with an increased relative risk of renal cell carcinoma (p less than 0.05). PMID:2720514

Genes expressed in dental enamel development are associated with molar-incisor hypomineralization.

PubMed

Jeremias, Fabiano; Koruyucu, Mine; Küchler, Erika C; Bayram, Merve; Tuna, Elif B; Deeley, Kathleen; Pierri, Ricardo A; Souza, Juliana F; Fragelli, Camila M B; Paschoal, Marco A B; Gencay, Koray; Seymen, Figen; Caminaga, Raquel M S; dos Santos-Pinto, Lourdes; Vieira, Alexandre R

2013-10-01

Genetic disturbances during dental development influence variation of number and shape of the dentition. In this study, we tested if genetic variation in enamel formation genes is associated with molar-incisor hypomineralization (MIH), also taking into consideration caries experience. DNA samples from 163 cases with MIH and 82 unaffected controls from Turkey, and 71 cases with MIH and 89 unaffected controls from Brazil were studied. Eleven markers in five genes [ameloblastin (AMBN), amelogenin (AMELX), enamelin (ENAM), tuftelin (TUFT1), and tuftelin-interacting protein 11 (TFIP11)] were genotyped by the TaqMan method. Chi-square was used to compare allele and genotype frequencies between cases with MIH and controls. In the Brazilian data, distinct caries experience within the MIH group was also tested for association with genetic variation in enamel formation genes. The ENAM rs3796704 marker was associated with MIH in both populations (Brazil: p=0.03; OR=0.28; 95% C.I.=0.06-1.0; Turkey: p=1.22e-012; OR=17.36; 95% C.I.=5.98-56.78). Associations between TFIP11 (p=0.02), ENAM (p=0.00001), and AMELX (p=0.01) could be seen with caries independent of having MIH or genomic DNA copies of Streptococcus mutans detected by real time PCR in the Brazilian sample. Several genes involved in enamel formation appear to contribute to MIH. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.

PubMed

Sims, Rebecca; van der Lee, Sven J; Naj, Adam C; Bellenguez, Céline; Badarinarayan, Nandini; Jakobsdottir, Johanna; Kunkle, Brian W; Boland, Anne; Raybould, Rachel; Bis, Joshua C; Martin, Eden R; Grenier-Boley, Benjamin; Heilmann-Heimbach, Stefanie; Chouraki, Vincent; Kuzma, Amanda B; Sleegers, Kristel; Vronskaya, Maria; Ruiz, Agustin; Graham, Robert R; Olaso, Robert; Hoffmann, Per; Grove, Megan L; Vardarajan, Badri N; Hiltunen, Mikko; Nöthen, Markus M; White, Charles C; Hamilton-Nelson, Kara L; Epelbaum, Jacques; Maier, Wolfgang; Choi, Seung-Hoan; Beecham, Gary W; Dulary, Cécile; Herms, Stefan; Smith, Albert V; Funk, Cory C; Derbois, Céline; Forstner, Andreas J; Ahmad, Shahzad; Li, Hongdong; Bacq, Delphine; Harold, Denise; Satizabal, Claudia L; Valladares, Otto; Squassina, Alessio; Thomas, Rhodri; Brody, Jennifer A; Qu, Liming; Sánchez-Juan, Pascual; Morgan, Taniesha; Wolters, Frank J; Zhao, Yi; Garcia, Florentino Sanchez; Denning, Nicola; Fornage, Myriam; Malamon, John; Naranjo, Maria Candida Deniz; Majounie, Elisa; Mosley, Thomas H; Dombroski, Beth; Wallon, David; Lupton, Michelle K; Dupuis, Josée; Whitehead, Patrice; Fratiglioni, Laura; Medway, Christopher; Jian, Xueqiu; Mukherjee, Shubhabrata; Keller, Lina; Brown, Kristelle; Lin, Honghuang; Cantwell, Laura B; Panza, Francesco; McGuinness, Bernadette; Moreno-Grau, Sonia; Burgess, Jeremy D; Solfrizzi, Vincenzo; Proitsi, Petra; Adams, Hieab H; Allen, Mariet; Seripa, Davide; Pastor, Pau; Cupples, L Adrienne; Price, Nathan D; Hannequin, Didier; Frank-García, Ana; Levy, Daniel; Chakrabarty, Paramita; Caffarra, Paolo; Giegling, Ina; Beiser, Alexa S; Giedraitis, Vilmantas; Hampel, Harald; Garcia, Melissa E; Wang, Xue; Lannfelt, Lars; Mecocci, Patrizia; Eiriksdottir, Gudny; Crane, Paul K; Pasquier, Florence; Boccardi, Virginia; Henández, Isabel; Barber, Robert C; Scherer, Martin; Tarraga, Lluis; Adams, Perrie M; Leber, Markus; Chen, Yuning; Albert, Marilyn S; Riedel-Heller, Steffi; Emilsson, Valur; Beekly, Duane; Braae, Anne; Schmidt, Reinhold; Blacker, Deborah; Masullo, Carlo; Schmidt, Helena; Doody, Rachelle S; Spalletta, Gianfranco; Longstreth, W T; Fairchild, Thomas J; Bossù, Paola; Lopez, Oscar L; Frosch, Matthew P; Sacchinelli, Eleonora; Ghetti, Bernardino; Yang, Qiong; Huebinger, Ryan M; Jessen, Frank; Li, Shuo; Kamboh, M Ilyas; Morris, John; Sotolongo-Grau, Oscar; Katz, Mindy J; Corcoran, Chris; Dunstan, Melanie; Braddel, Amy; Thomas, Charlene; Meggy, Alun; Marshall, Rachel; Gerrish, Amy; Chapman, Jade; Aguilar, Miquel; Taylor, Sarah; Hill, Matt; Fairén, Mònica Díez; Hodges, Angela; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Daniilidou, Makrina; Uphill, James; Patel, Yogen; Hughes, Joseph T; Lord, Jenny; Turton, James; Hartmann, Annette M; Cecchetti, Roberta; Fenoglio, Chiara; Serpente, Maria; Arcaro, Marina; Caltagirone, Carlo; Orfei, Maria Donata; Ciaramella, Antonio; Pichler, Sabrina; Mayhaus, Manuel; Gu, Wei; Lleó, Alberto; Fortea, Juan; Blesa, Rafael; Barber, Imelda S; Brookes, Keeley; Cupidi, Chiara; Maletta, Raffaele Giovanni; Carrell, David; Sorbi, Sandro; Moebus, Susanne; Urbano, Maria; Pilotto, Alberto; Kornhuber, Johannes; Bosco, Paolo; Todd, Stephen; Craig, David; Johnston, Janet; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Fox, Nick C; Hardy, John; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Asthana, Sanjay; Atwood, Craig S; Baldwin, Clinton T; Barnes, Lisa L; Barral, Sandra; Beach, Thomas G; Becker, James T; Bigio, Eileen H; Bird, Thomas D; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Burns, Jeffrey M; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carlsson, Cynthia M; Carney, Regina M; Carrasquillo, Minerva M; Carroll, Steven L; Diaz, Carolina Ceballos; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; Dick, Malcolm; Duara, Ranjan; Evans, Denis A; Faber, Kelley M; Fallon, Kenneth B; Fardo, David W; Farlow, Martin R; Ferris, Steven; Foroud, Tatiana M; Galasko, Douglas R; Gearing, Marla; Geschwind, Daniel H; Gilbert, John R; Graff-Radford, Neill R; Green, Robert C; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Honig, Lawrence S; Huentelman, Matthew J; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Abner, Erin; Jin, Lee-Way; Jun, Gyungah; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Ge; Lieberman, Andrew P; Lunetta, Kathryn L; Lyketsos, Constantine G; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Morris, John C; Murrell, Jill R; Myers, Amanda J; O'Bryant, Sid; Olichney, John M; Pankratz, Vernon S; Parisi, Joseph E; Paulson, Henry L; Perry, William; Peskind, Elaine; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rogaeva, Ekaterina; Rosen, Howard J; Rosenberg, Roger N; Sager, Mark A; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Swerdlow, Russell H; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Wilhelmsen, Kirk C; Williamson, Jennifer; Wingo, Thomas S; Woltjer, Randall L; Wright, Clinton B; Yu, Chang-En; Yu, Lei; Garzia, Fabienne; Golamaully, Feroze; Septier, Gislain; Engelborghs, Sebastien; Vandenberghe, Rik; De Deyn, Peter P; Fernadez, Carmen Muñoz; Benito, Yoland Aladro; Thonberg, Hakan; Forsell, Charlotte; Lilius, Lena; Kinhult-Stählbom, Anne; Kilander, Lena; Brundin, RoseMarie; Concari, Letizia; Helisalmi, Seppo; Koivisto, Anne Maria; Haapasalo, Annakaisa; Dermecourt, Vincent; Fievet, Nathalie; Hanon, Olivier; Dufouil, Carole; Brice, Alexis; Ritchie, Karen; Dubois, Bruno; Himali, Jayanadra J; Keene, C Dirk; Tschanz, JoAnn; Fitzpatrick, Annette L; Kukull, Walter A; Norton, Maria; Aspelund, Thor; Larson, Eric B; Munger, Ron; Rotter, Jerome I; Lipton, Richard B; Bullido, María J; Hofman, Albert; Montine, Thomas J; Coto, Eliecer; Boerwinkle, Eric; Petersen, Ronald C; Alvarez, Victoria; Rivadeneira, Fernando; Reiman, Eric M; Gallo, Maura; O'Donnell, Christopher J; Reisch, Joan S; Bruni, Amalia Cecilia; Royall, Donald R; Dichgans, Martin; Sano, Mary; Galimberti, Daniela; St George-Hyslop, Peter; Scarpini, Elio; Tsuang, Debby W; Mancuso, Michelangelo; Bonuccelli, Ubaldo; Winslow, Ashley R; Daniele, Antonio; Wu, Chuang-Kuo; Peters, Oliver; Nacmias, Benedetta; Riemenschneider, Matthias; Heun, Reinhard; Brayne, Carol; Rubinsztein, David C; Bras, Jose; Guerreiro, Rita; Al-Chalabi, Ammar; Shaw, Christopher E; Collinge, John; Mann, David; Tsolaki, Magda; Clarimón, Jordi; Sussams, Rebecca; Lovestone, Simon; O'Donovan, Michael C; Owen, Michael J; Behrens, Timothy W; Mead, Simon; Goate, Alison M; Uitterlinden, Andre G; Holmes, Clive; Cruchaga, Carlos; Ingelsson, Martin; Bennett, David A; Powell, John; Golde, Todd E; Graff, Caroline; De Jager, Philip L; Morgan, Kevin; Ertekin-Taner, Nilufer; Combarros, Onofre; Psaty, Bruce M; Passmore, Peter; Younkin, Steven G; Berr, Claudine; Gudnason, Vilmundur; Rujescu, Dan; Dickson, Dennis W; Dartigues, Jean-François; DeStefano, Anita L; Ortega-Cubero, Sara; Hakonarson, Hakon; Campion, Dominique; Boada, Merce; Kauwe, John Keoni; Farrer, Lindsay A; Van Broeckhoven, Christine; Ikram, M Arfan; Jones, Lesley; Haines, Jonathan L; Tzourio, Christophe; Launer, Lenore J; Escott-Price, Valentina; Mayeux, Richard; Deleuze, Jean-François; Amin, Najaf; Holmans, Peter A; Pericak-Vance, Margaret A; Amouyel, Philippe; van Duijn, Cornelia M; Ramirez, Alfredo; Wang, Li-San; Lambert, Jean-Charles; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D

2017-09-01

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10 -4 ) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10 -8 ) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10 -10 , odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAF controls = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10 -10 , OR = 1.43, MAF cases = 0.011, MAF controls = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10 -14 , OR = 1.67, MAF cases = 0.0143, MAF controls = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

Physical activity, opportunity for reinfection, and sibling history of heart disease as risk factors for Chagas' cardiopathy.

PubMed

Zicker, F; Smith, P G; Netto, J C; Oliveira, R M; Zicker, E M

1990-11-01

A case-control study was conducted to examine whether physical activity, sibling history of heart disease (HHD), and length of residence in an area endemic for Chagas' disease were associated with the risk of developing Chagas' cardiopathy. Two hundred forty-seven cases of Chagas' heart disease and 345 seropositive subjects with normal ECG (controls) were selected in a population survey in Goiânia, Brazil. Prevalence ratios for exposure variables were estimated for cases in relation to controls and for subgroups of seropositives with selected ECG abnormalities in relation to controls. Increasing age and male sex were consistently and significantly related to an increased risk of ECG abnormalities. HHD was significantly associated with ECG alterations in 3 of the 5 comparison subgroups (any ECG alteration, right bundle branch block, and left anterior hemiblock). No association was found between length of residence in an area endemic, physical activity, and ECG abnormalities. A sample of 529 seronegative subjects were also examined and the interaction between exposure variables and seropositivity was tested to assess whether the associations found were specific for seropositives. Males were at greater risk of any ECG alteration and left anterior hemiblock in relation to females if they were seropositive. An increasing risk of ventricular premature beats with age was clearer for seropositive than for seronegative subjects. Subjects with HHD were at an increased risk of ECG abnormalities and this was greater in those with a positive serological test (P less than 0.05). The findings suggest a possible geographical clustering or a familial aggregation of cases of Chagas' heart disease.

Lack of association between Toxoplasma gondii exposure and depression in pregnant women: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Martínez-Martínez, Ana Liliana; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Castillo-Orona, Juan Manuel; Salas-Martínez, Carlos; Sifuentes-Álvarez, Antonio; Sandoval-Carrillo, Ada Agustina; Salas-Pacheco, José M; Liesenfeld, Oliver; Antuna-Salcido, Elizabeth Irasema

2017-03-06

Very little is known about the link of T. gondii infection and depression. Through an age-, gender-, and month of pregnancy-matched case-control study, we determined the association of T. gondii infection and depression in pregnant women. We studied 200 pregnant women with depression and 200 pregnant women without depression attended in a public hospital in Durango City, Mexico. Pregnant women were tested for the presence of anti-Toxoplasma IgG antibodies using an enzyme-linked immunoassay (EIA), and IgG seropositive women were further tested for the presence of IgM using an EIA. IgM positivity by EIA was further analyzed by enzyme-linked fluorescence assay (ELFA). Anti-T. gondii IgG antibodies were found in 9 (4.5%) of the 200 cases and in 12 (6.0%) of the 200 controls (OR = 0.73; 95% CI: 0.30-1.79; P = 0.50). The frequency of high (>150 IU/ml) anti-T. gondii IgG levels was similar in cases and in controls (OR = 1.20; 95% CI: 0.36-4.01; P = 0.75). Two women were positive for IgM by EIA but both were negative by ELFA. We did not find serological evidence of an association between T. gondii infection and depression in pregnant women attended in a public hospital in Durango City, Mexico. Since an association of T. gondii and depression in pregnancy has been reported in the U.S. previously, further research to elucidate the role of T. gondii in prenatal depression should be conducted.

Serotonin-related FEV gene variant in the sudden infant death syndrome is a common polymorphism in the African-American population.

PubMed

Broadbelt, Kevin G; Barger, Melissa A; Paterson, David S; Holm, Ingrid A; Haas, Elisabeth A; Krous, Henry F; Kinney, Hannah C; Markianos, Kyriacos; Beggs, Alan H

2009-12-01

An important subset of the sudden infant death syndrome (SIDS) is associated with multiple serotonergic (5-HT) abnormalities in regions of the medulla oblongata. The mouse ortholog of the fifth Ewing variant gene (FEV) is critical for 5-HT neuronal development. A putatively rare intronic variant [IVS2-191_190insA, here referred to as c.128-(191_192)dupA] has been reported as a SIDS-associated mutation in an African-American population. We tested this association in an independent dataset: 137 autopsied cases (78 SIDS, 59 controls) and an additional 296 control DNA samples from Coriell Cell Repositories. In addition to the c.128-(191_192)dupA variant, we observed an associated single-base deletion [c.128-(301-306)delG] in a subset of the samples. Neither of the two FEV variants showed significant association with SIDS in either the African-American subgroup or the overall cohort. Although we found a significant association of c.128-(191_192)dupA with SIDS when San Diego Hispanic SIDS cases were compared with San Diego Hispanic controls plus Mexican controls (p = 0.04), this became nonsignificant after multiple testing correction. Among Coriell controls, 33 of 99 (33%) African-American and 0 of 197 (0%) of the remaining controls carry the polymorphism (c.128-(191_192)dupA). The polymorphism seems to be a common, likely nonpathogenic, variant in the African-American population.

Forced sexual intercourse and its association with HIV status among people attending HIV Voluntary Counseling and Testing in a healthcare center in Kinshasa (DRC).

PubMed

Burgueño, Eduardo; Carlos, Silvia; Lopez-Del Burgo, Cristina; Osorio, Alfonso; Stozek, Maria; Ndarabu, Adolphe; Muamba, Philémon; Tshisuaka, Philomene; De Irala, Jokin

2017-01-01

Sexual violence, an HIV determinant, is an integrated behavior in the D.R.Congo. We aimed to analyze the prevalence of forced sexual intercourse (FSI) among people receiving HIV Voluntary Counseling and Testing in a hospital in Kinshasa, and its association with socio-demographics, behaviors and HIV status. Case-control study (2010-2012). Two-hundred and seventy-four cases with a new HIV+ test and 1,340 controls with an HIV- test were interviewed about HIV-related knowledge, attitudes and behaviors, including FSI. Thirty-four percent of the participants declared having had FSI (38% of women and 32% of men). Being a woman, aged 25-49 and reporting multiple sexual partners were associated with reporting FSI. For men, being single was protective against FSI; and cohabiting, having a high socioeconomic status, and alcohol consumption increased the odds. For women, being single, divorced/separated and widow was associated with reporting FSI. A significant positive association was found between FSI and an HIV positive test. Among our Congolese population, FSI was strongly associated with HIV infection and it was also associated with alcohol consumption and multiple sexual partnerships, other key HIV determinants. These behaviors need to be identified as potential risk factors of FSI during counseling interventions. Researchers, practitioners and decision-makers should work together to get violence prevention integrated into health, social and educational policies.

Male condom use, multiple sexual partners and HIV: a prospective case-control study in Kinshasa (DRC).

PubMed

Carlos, Silvia; Lopez-Del Burgo, Cristina; Burgueño, Eduardo; Martinez-Gonzalez, Miguel Angel; Osorio, Alfonso; Ndarabu, Adolphe; Passabosc, Clément; de Irala, Jokin

2017-06-01

In the Democratic Republic of Congo no previous studies have assessed the factors associated with different patterns of condom use and with multiple sexual partners, and the association between condom use simultaneously taking into account multiple sexual partnerships, and HIV infection. We carried out a prospective case-control study. From December 2010 until June 2012, 1630 participants aged 15-49 getting HIV Voluntary Counseling and Testing in a hospital in Kinshasa were selected. Cases were new HIV diagnosis and controls were HIV-negative participants detected along the study period. We recruited 274 cases and 1340 controls that were interviewed about HIV-related knowledge, attitudes and behaviours. Among cases there was a high prevalence of multiple lifetime and concurrent sexual partnerships (89.8% and 20.4%, respectively) and most cases never used condoms with only 1.5% using them consistently. Condom use and multiple partnerships were associated with male, single and high-educated participants. An association was found between multiple lifetime partners and 'any condom use' (OR = 2.99; 95%CI: 2.14-4.19) but not with consistent use. Both having two or more multiple concurrent sexual partners or not using condoms were variables similarly and highly associated to HIV risk. The association found between having two or more concurrent sexual partners and HIV was slightly higher (OR = 3.58, 95%CI:2.31-5.56) than the association found between never condom use and HIV (OR = 3.38, 95%CI:1.15-9.93). We found a high prevalence of multiple lifetime sexual partners and an extremely high prevalence of inconsistent condom use, both strongly associated with HIV seropositivity. Local programmes would benefit from comprehensive interventions targeting all behavioural and sociocultural determinants.

Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case-parent triad study in a Norwegian-Swedish population.

PubMed

Kristiansen, W; Andreassen, K E; Karlsson, R; Aschim, E L; Bremnes, R M; Dahl, O; Fosså, S D; Klepp, O; Langberg, C W; Solberg, A; Tretli, S; Adami, H-O; Wiklund, F; Grotmol, T; Haugen, T B

2012-05-01

Testicular germ cell tumour (TGCT) is the most common cancer in young men, and an imbalance between the estrogen and androgen levels in utero is hypothesized to influence TGCT risk. Thus, polymorphisms in genes involved in the action of sex hormones may contribute to variability in an individual's susceptibility to TGCT. We conducted a Norwegian-Swedish case-parent study. A total of 105 single-nucleotide polymorphisms (SNPs) in 20 sex hormone pathway genes were genotyped using Sequenom MassArray iPLEX Gold, in 831 complete triads and 474 dyads. To increase the statistical power, the analysis was expanded to include 712 case singletons and 3922 Swedish controls, thus including triads, dyads and the case-control samples in a single test for association. Analysis for allelic associations was performed with the UNPHASED program, using a likelihood-based association test for nuclear families with missing data, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. False discovery rate (FDR) was used to adjust for multiple testing. Five genetic variants across the ESR2 gene [encoding estrogen receptor beta (ERβ)] were statistically significantly associated with the risk of TGCT. In the case-parent analysis, the markers rs12434245 and rs10137185 were associated with a reduced risk of TGCT (OR = 0.66 and 0.72, respectively; both FDRs <5%), whereas rs2978381 and rs12435857 were associated with an increased risk of TGCT (OR = 1.21 and 1.19, respectively; both FDRs <5%). In the combined case-parent/case-control analysis, rs12435857 and rs10146204 were associated with an increased risk of TGCT (OR = 1.15 and 1.13, respectively; both FDRs <5%), whereas rs10137185 was associated with a reduced risk of TGCT (OR = 0.79, FDR <5%). In addition, we found that three genetic variants in CYP19A1 (encoding aromatase) were statistically significantly associated with the risk of TGCT in the case-parent analysis. The T alleles of the rs2414099, rs8025374 and rs3751592 SNPs were associated with an increased risk of TGCT (OR = 1.30, 1.30 and 1.21, respectively; all FDRs <5%). We found no statistically significant differences in allelic effect estimates between parental inherited genetic variation in the sex hormone pathways and TGCT risk in the offspring, and no evidence of heterogeneity between seminomas and non-seminomas, or between the Norwegian and the Swedish population, in any of the SNPs examined. Our findings provide support for ERβ and aromatase being implicated in the aetiology of TGCT. Exploring the functional role of the TGCT risk-associated SNPs will further elucidate the biological mechanisms involved.

Behavioral Problems and Childhood Epilepsy: Parent vs Child Perspectives.

PubMed

Eom, Soyong; Caplan, Rochelle; Berg, Anne T

2016-12-01

To test whether the reported association between pediatric epilepsy and behavioral problems may be distorted by the use of parental proxy report instruments. Children in the Connecticut Study of Epilepsy were assessed 8-9 years after their epilepsy diagnosis (time-1) with the parent-proxy Child Behavior Check List (CBCL) (ages 6-18 years) or the Young Adult Self-Report (≥18 years of age). For children <18 years of age, parents also completed the Child Health Questionnaire, which contains scales for impact of child's illness on the parents. The same study subjects completed the Adult Self-Report 6-8 years later (time-2). Sibling controls were also tested. Case-control differences were examined for evidence suggesting more behavioral problems in cases with epilepsy than in controls based on proxy- vs self-report measures. At time-1, parent-proxy CBCL scores were significantly higher (worse) for cases than controls (n = 140 matched pairs). After adjustment for Child Health Questionnaire scales reflecting parent emotional and time impact, only 1 case-control difference on the CBCL remained significant. Self-reported Young Adult Self-Report scores did not differ between cases and controls (n = 42 pairs). At time-2, there were no significant self-reported case-control differences on the Adult Self-Report (n = 105 pairs). Parent-proxy behavior measures appear to be influenced by the emotional impact of epilepsy on parents. This may contribute to apparent associations between behavioral problems and childhood epilepsy. Self-report measures in older adolescents (>18 years of age) and young adults do not confirm parental perceptions. Evidence suggesting more behavioral problems in children with epilepsy should be interpreted in light of the source of information. Copyright © 2016 Elsevier Inc. All rights reserved.

The Influence of Screening for Precancerous Lesions on Family-Based Genetic Association Tests: An Example of Colorectal Polyps and Cancer.

PubMed

Schmit, Stephanie L; Figueiredo, Jane C; Cortessis, Victoria K; Thomas, Duncan C

2015-10-15

Unintended consequences of secondary prevention include potential introduction of bias into epidemiologic studies estimating genotype-disease associations. To better understand such bias, we simulated a family-based study of colorectal cancer (CRC), which can be prevented by resecting screen-detected polyps. We simulated genes related to CRC development through risk of polyps (G1), risk of CRC but not polyps (G2), and progression from polyp to CRC (G3). Then, we examined 4 analytical strategies for studying diseases subject to secondary prevention, comparing the following: 1) CRC cases with all controls, without adjusting for polyp history; 2) CRC cases with controls, adjusting for polyp history; 3) CRC cases with only polyp-free controls; and 4) cases with either CRC or polyps with controls having neither. Strategy 1 yielded estimates of association between CRC and each G that were not substantially biased. Strategies 2-4 yielded biased estimates varying in direction according to analysis strategy and gene type. Type I errors were correct, but strategy 1 provided greater power for estimating associations with G2 and G3. We also applied each strategy to case-control data from the Colon Cancer Family Registry (1997-2007). Generally, the best analytical option balancing bias and power is to compare all CRC cases with all controls, ignoring polyps. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case-control study.

PubMed

Colebunders, Robert; Mandro, Michel; Mokili, John L; Mucinya, Gisele; Mambandu, Germain; Pfarr, Kenneth; Reiter-Owona, Ingrid; Hoerauf, Achim; Tepage, Floribert; Levick, Bethanie; Begon, Michael; Laudisoit, Anne

2016-08-01

The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis. In June 2014, a case-control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n=59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n=61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case-control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy. Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42-170; p<0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p=0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p=0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2-125.8; p<0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6-103.7; p=0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5-77.3; p=0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and controls. A Loa loa infestation was found in only one case and one control by PCR and Giemsa smear. Antibodies to Taenia solium, Toxocara, and Trypanosoma sp were not detected in any of the participants. In an age-matched case-control analysis, 16/18 (89%) cases had not taken ivermectin the year before they developed epilepsy, compared to 7/18 (39%) controls that same year (p=0.002). These data suggest that frequent activities at rivers known to be blackfly breeding sites and a historical lack of ivermectin treatment were risk factors for epilepsy in this onchocerciasis endemic area. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Association between age and high-risk human papilloma virus in Mexican oral cancer patients.

PubMed

González-Ramírez, I; Irigoyen-Camacho, M E; Ramírez-Amador, V; Lizano-Soberón, M; Carrillo-García, A; García-Carrancá, A; Sánchez-Pérez, Y; Méndez-Martínez, R; Granados-García, M; Ruíz-Godoy, Lm; García-Cuellar, Cm

2013-11-01

Studies reporting low prevalence of HPV in OSCC with declining age at presentation are increasing. The aim of this study was to determine the prevalence of HPV in a group of OSCC cases and controls in a Mexican population. The matched case-control study included 80 OSCC cases and 320 controls. HPV/DNA presence was evaluated through PCR amplification using three sets of consensus primers for the L1 gene. A conditional logistic regression analysis was carried out for the matched OSCC cases and controls. Interactions between risk factors and OCSS were tested in the construction process of the models. HPV prevalence was 5% in OSCC cases and 2.5% in controls. HPV-detected types were 16, 18 and 56. According to conditional logistics regression model, an association was detected between HR-HPV and OSCC. All HR-HPV-positive OSCC cases corresponded to young patients (<45 years), non-smokers and non-alcohol drinkers. The HR-HPV can be a contributing factor to oral carcinogenesis, especially in younger individuals without known risk factors such as tobacco and alcohol. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Preeclampsia does not share common risk alleles in 9p21 with coronary artery disease and type 2 diabetes.

PubMed

Kaartokallio, Tea; Lokki, A Inkeri; Peterson, Hanna; Kivinen, Katja; Hiltunen, Leena; Salmela, Elina; Lappalainen, Tuuli; Maanselkä, Paula; Heino, Sanna; Knuutila, Sakari; Sayed, Ayat; Poston, Lucilla; Brennecke, Shaun P; Johnson, Matthew P; Morgan, Linda; Moses, Eric K; Kere, Juha; Laivuori, Hannele

2016-08-01

Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia. We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets. Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts. Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia. Key Message Chromosome 9p21 is not associated with preeclampsia.

Association between Zika virus infection and microcephaly in Brazil, January to May, 2016: preliminary report of a case-control study.

PubMed

de Araújo, Thalia Velho Barreto; Rodrigues, Laura Cunha; de Alencar Ximenes, Ricardo Arraes; de Barros Miranda-Filho, Demócrito; Montarroyos, Ulisses Ramos; de Melo, Ana Paula Lopes; Valongueiro, Sandra; de Albuquerque, Maria de Fátima Pessoa Militão; Souza, Wayner Vieira; Braga, Cynthia; Filho, Sinval Pinto Brandão; Cordeiro, Marli Tenório; Vazquez, Enrique; Di Cavalcanti Souza Cruz, Danielle; Henriques, Cláudio Maierovitch Pessanha; Bezerra, Luciana Caroline Albuquerque; da Silva Castanha, Priscila Mayrelle; Dhalia, Rafael; Marques-Júnior, Ernesto Torres Azevedo; Martelli, Celina Maria Turchi

2016-12-01

The microcephaly epidemic, which started in Brazil in 2015, was declared a Public Health Emergency of International Concern by WHO in 2016. We report the preliminary results of a case-control study investigating the association between microcephaly and Zika virus infection during pregnancy. We did this case-control study in eight public hospitals in Recife, Brazil. Cases were neonates with microcephaly. Two controls (neonates without microcephaly), matched by expected date of delivery and area of residence, were selected for each case. Serum samples of cases and controls and cerebrospinal fluid samples of cases were tested for Zika virus-specific IgM and by quantitative RT-PCR. Laboratory-confirmed Zika virus infection during pregnancy was defined as detection of Zika virus-specific IgM or a positive RT-PCR result in neonates. Maternal serum samples were tested by plaque reduction neutralisation assay for Zika virus and dengue virus. We estimated crude odds ratios (ORs) and 95% CIs using a median unbiased estimator for binary data in an unconditional logistic regression model. We estimated ORs separately for cases with and without radiological evidence of brain abnormalities. Between Jan 15, 2016, and May 2, 2016, we prospectively recruited 32 cases and 62 controls. 24 (80%) of 30 mothers of cases had Zika virus infection compared with 39 (64%) of 61 mothers of controls (p=0·12). 13 (41%) of 32 cases and none of 62 controls had laboratory-confirmed Zika virus infection; crude overall OR 55·5 (95% CI 8·6-∞); OR 113·3 (95% CI 14·5-∞) for seven cases with brain abnormalities; and OR 24·7 (95% CI 2·9-∞) for four cases without brain abnormalities. Our data suggest that the microcephaly epidemic is a result of congenital Zika virus infection. We await further data from this ongoing study to assess other potential risk factors and to confirm the strength of association in a larger sample size. Brazilian Ministry of Health, Pan American Health Organization, and Enhancing Research Activity in Epidemic Situations. Copyright This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.

Risk factors for syphilis infection among pregnant women: results of a case‐control study in Shenzhen, China

PubMed Central

Zhou, Hua; Chen, Xiang‐Sheng; Hong, Fu‐Chang; Pan, Peng; Yang, Fan; Cai, Yu‐Mao; Yin, Yue‐Ping; Peeling, Rosanna W; Mabey, David

2007-01-01

Background China has been experiencing a rapidly growing syphilis epidemic since the early 1990s, with the reported incidence of congenital syphilis increasing from 0.01 cases per 100 000 live births in 1991 to 19.7 cases per 100 000 live births in 2005. Detailed studies of risk factors for syphilis in pregnant women are needed to inform new preventive interventions. Objective To investigate factors associated with recent syphilis infection among pregnant women and recommend strategies for improved preventive interventions in the community. Methods A case–control study was conducted among women attending antenatal clinics in Shenzhen City, South China. Cases were antenatal clinic women testing positive for early syphilis, based on laboratory results, with those testing negative being controls. All participants completed the same anonymous questionnaire covering demographics, lifestyle, sexual behaviour, and sexual partnerships. Results 129 cases and 345 controls were recruited. Syphilis was significantly associated with unmarried status, less education, multiple sex partners, travel of sex partner in the past 12 months, a history of induced abortion, and previous sexually transmitted infections. Overall, there were no differences between syphilis‐positive and negative women in household registration status (hukou), living district and duration in Shenzhen, monthly income, and age at first sex. Conclusions Many demographic and behavioural risk factors are associated with syphilis among pregnant women. In the government congenital syphilis control programme, comprehensive preventive interventions should be provided in all clinical settings in addition to the current procedures for syphilis screening among antenatal women. PMID:17675391

[Voice disorders related to job stress in teaching: a case-control study].

PubMed

Giannini, Susana Pimentel Pinto; Latorre, Maria do Rosário Dias de Oliveira; Ferreira, Leslie Piccolotto

2012-11-01

This case-control study aimed to test the association between voice disorders and job stress among public schoolteachers in São Paulo, Brazil. The groups consisted of teachers with (n = 165) and without (n = 105) voice-related complaints. Both groups answered the questionnaires Conditions of Vocal Production and Job Stress Scale. Analysis of cases and controls showed comparable samples, differing only by vocal symptoms. There was a statistically significant difference between cases and controls in relation to job stress involving high strain (OR = 2.1; 95%CI: 1.1-3.9), which places high demands combined with low job control. High strain in cases in this study represents the highest risk of physical and mental disorders for teachers. Loss of voice prevents teachers from continuing in their professional role, eliminates their professional identity, and jeopardizes their career.

Clinical factors associated with readmission for postpartum hypertension in women with pregnancy-related hypertension: a nested case control study.

PubMed

Hirshberg, A; Levine, L D; Srinivas, S K

2016-05-01

To evaluate the association between mode of delivery and length of labor on readmission for postpartum hypertension in women with pregnancy-related hypertension. Nested case control study within a cohort of 99 women with pregnancy-related hypertension who delivered at our institution between 2005 and 2009. Data were abstracted for clinical and labor information. Mode of delivery and length of labor were compared between women with previously diagnosed pregnancy-related hypertension readmitted within 4 weeks post partum (25 cases) and those not readmitted (74 controls). Categorical and continuous variables were compared using χ(2) and T-tests, respectively. Multivariable logistic regression controlled for confounders. Hypertension readmission was not associated with mode of delivery (cases: 10(40%) spontaneous vaginal delivery, 15(60%) cesarean delivery; controls: 38(51%) spontaneous vaginal delivery, 36(49%) cesarean delivery, P=0.33). Length of labor appeared longer in cases, with a trend toward significance (median: 15.5 [7,28] h vs 10.75 [5.8,15.9] h, P=0.12) and was significantly associated with readmission after controlling for delivery mode, induction and parity (adjusted odds ratio=1.06 [1 to 1.12], P=0.048). Readmitted patients were less likely to have initially been started on antihypertensive medications after controlling for age, race and chronic hypertension (adjusted odds ratio=0.23 [0.06 to 0.88], P=0.03). Postpartum readmission for hypertension in women with known pregnancy-related hypertension is not associated with mode of delivery, appears increased in those with longer length of labor and decreased in those initially started on antihypertensive medications. This provides targets for future research to continue to improve transitions of care and reduce preventable readmissions.

Clinical factors associated with readmission for postpartum hypertension in women with pregnancy-related hypertension: a nested case control study

PubMed Central

Hirshberg, A; Levine, LD; Srinivas, SK

2017-01-01

Objective To evaluate the association between mode of delivery and length of labor on readmission for postpartum hypertension in women with pregnancy-related hypertension. Study Design Nested case control study within a cohort of 99 women with pregnancy-related hypertension who delivered at our institution between 2005 and 2009. Data were abstracted for clinical and labor information. Mode of delivery and length of labor were compared between women with previously diagnosed pregnancy-related hypertension readmitted within 4 weeks post partum (25 cases) and those not readmitted (74 controls). Categorical and continuous variables were compared using χ2 and T-tests, respectively. Multivariable logistic regression controlled for confounders. Result Hypertension readmission was not associated with mode of delivery (cases: 10(40%) spontaneous vaginal delivery, 15(60%) cesarean delivery; controls: 38(51%) spontaneous vaginal delivery, 36(49%) cesarean delivery, P=0.33). Length of labor appeared longer in cases, with a trend toward significance (median: 15.5 [7,28] h vs 10.75 [5.8,15.9] h, P=0.12) and was significantly associated with readmission after controlling for delivery mode, induction and parity (adjusted odds ratio = 1.06 [1 to 1.12], P = 0.048). Readmitted patients were less likely to have initially been started on antihypertensive medications after controlling for age, race and chronic hypertension (adjusted odds ratio = 0.23 [0.06 to 0.88], P=0.03). Conclusion Postpartum readmission for hypertension in women with known pregnancy-related hypertension is not associated with mode of delivery, appears increased in those with longer length of labor and decreased in those initially started on antihypertensive medications. This provides targets for future research to continue to improve transitions of care and reduce preventable readmissions. PMID:26765549

Regulatory T-cell activity but not conventional HIV-specific T-cell responses are associated with protection from HIV-1 infection

PubMed Central

Pattacini, Laura; Baeten, Jared M.; Thomas, Katherine K.; Fluharty, Tayler R.; Murnane, Pamela M.; Donnell, Deborah; Bukusi, Elizabeth; Ronald, Allan; Mugo, Nelly; Lingappa, Jairam R.; Celum, Connie; McElrath, M. Juliana; Lund, Jennifer M.

2015-01-01

Objective Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated upon HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4+ T-cells, thereby diminishing the likelihood of infection. Methods To test these hypotheses, we conducted a prospective study among high-risk heterosexual men and women, and tested peripheral blood samples from individuals who subsequently acquired HIV-1 during follow-up (cases) and from a subset of those who remained HIV-1 uninfected (controls). Results We found no difference in HIV-1-specific immune responses between cases and controls, but Treg frequency was higher in controls as compared to cases and was negatively associated with frequency of effector memory CD4+ T-cells. Conclusions Our findings support the hypothesis that low immune activation assists in protection from HIV-1 infection. PMID:26656786

Breast cancer risk and genetic ancestry: a case-control study in Uruguay.

PubMed

Bonilla, Carolina; Bertoni, Bernardo; Hidalgo, Pedro C; Artagaveytia, Nora; Ackermann, Elizabeth; Barreto, Isabel; Cancela, Paula; Cappetta, Mónica; Egaña, Ana; Figueiro, Gonzalo; Heinzen, Silvina; Hooker, Stanley; Román, Estela; Sans, Mónica; Kittles, Rick A

2015-01-01

Uruguay exhibits one of the highest rates of breast cancer in Latin America, similar to those of developed nations, the reasons for which are not completely understood. In this study we investigated the effect that ancestral background has on breast cancer susceptibility among Uruguayan women. We carried out a case-control study of 328 (164 cases, 164 controls) women enrolled in public hospitals and private clinics across the country. We estimated ancestral proportions using a panel of nuclear and mitochondrial ancestry informative markers (AIMs) and tested their association with breast cancer risk. Nuclear individual ancestry in cases was (mean ± SD) 9.8 ± 7.6% African, 13.2 ± 10.2% Native American and 77.1 ± 13.1% European, and in controls 9.1 ± 7.5% African, 14.7 ± 11.2% Native American and 76.2 ± 14.2% European. There was no evidence of a difference in nuclear or mitochondrial ancestry between cases and controls. However, European mitochondrial haplogroup H was associated with breast cancer (OR = 2.0; 95% CI 1.1, 3.5). We have not found evidence that overall genetic ancestry differs between breast cancer patients and controls in Uruguay but we detected an association of the disease with a European mitochondrial lineage, which warrants further investigation.

Association of leptin and insulin resistance in PCOS: A case-controlled study.

PubMed

Namavar Jahromi, Bahia; Dabaghmanesh, Mohammad Hassan; Parsanezhad, Mohammad Ebrahim; Fatehpoor, Faranak

2017-07-01

Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m 2 ) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (p<0.001) and to age in non-PCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (p<0.001), QUICKI (p<0.001), FI (p=.002), and FBS (p=0.02). BMI and IR have positive association with serum leptin in PCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR.

Genetic variation in cell death genes and risk of non-Hodgkin lymphoma.

PubMed

Schuetz, Johanna M; Daley, Denise; Graham, Jinko; Berry, Brian R; Gallagher, Richard P; Connors, Joseph M; Gascoyne, Randy D; Spinelli, John J; Brooks-Wilson, Angela R

2012-01-01

Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5(th) highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility. We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate. Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63-4.82]; p(F) = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.

An ImmunoChip study of multiple sclerosis risk in African Americans

PubMed Central

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J.; Moré, Jayaji M.; Gourraud, Pierre-Antoine; McCauley, Jacob L.; Beecham, Ashley H.; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A. C.; Onengut-Gumuscu, Suna; Rich, Stephen S.; Hauser, Stephen L.; Sawcer, Stephen

2015-01-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10−4), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10−5). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. PMID:25818868

An ImmunoChip study of multiple sclerosis risk in African Americans.

PubMed

Isobe, Noriko; Madireddy, Lohith; Khankhanian, Pouya; Matsushita, Takuya; Caillier, Stacy J; Moré, Jayaji M; Gourraud, Pierre-Antoine; McCauley, Jacob L; Beecham, Ashley H; Piccio, Laura; Herbert, Joseph; Khan, Omar; Cohen, Jeffrey; Stone, Lael; Santaniello, Adam; Cree, Bruce A C; Onengut-Gumuscu, Suna; Rich, Stephen S; Hauser, Stephen L; Sawcer, Stephen; Oksenberg, Jorge R

2015-06-01

The aims of this study were: (i) to determine to what degree multiple sclerosis-associated loci discovered in European populations also influence susceptibility in African Americans; (ii) to assess the extent to which the unique linkage disequilibrium patterns in African Americans can contribute to localizing the functionally relevant regions or genes; and (iii) to search for novel African American multiple sclerosis-associated loci. Using the ImmunoChip custom array we genotyped 803 African American cases with multiple sclerosis and 1516 African American control subjects at 130 135 autosomal single nucleotide polymorphisms. We conducted association analysis with rigorous adjustments for population stratification and admixture. Of the 110 non-major histocompatibility complex multiple sclerosis-associated variants identified in Europeans, 96 passed stringent quality control in our African American data set and of these, >70% (69) showed over-representation of the same allele amongst cases, including 21 with nominally significant evidence for association (one-tailed test P < 0.05). At a further eight loci we found nominally significant association with an alternate correlated risk-tagging single nucleotide polymorphism from the same region. Outside the regions known to be associated in Europeans, we found seven potentially associated novel candidate multiple sclerosis variants (P < 10(-4)), one of which (rs2702180) also showed nominally significant evidence for association (one-tailed test P = 0.034) in an independent second cohort of 620 African American cases and 1565 control subjects. However, none of these novel associations reached genome-wide significance (combined P = 6.3 × 10(-5)). Our data demonstrate substantial overlap between African American and European multiple sclerosis variants, indicating common genetic contributions to multiple sclerosis risk. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Risk Factors for Podoconiosis: Kamwenge District, Western Uganda, September 2015.

PubMed

Kihembo, Christine; Masiira, Ben; Lali, William Z; Matwale, Gabriel K; Matovu, Joseph K B; Kaharuza, Frank; Ario, Alex R; Nabukenya, Immaculate; Makumbi, Issa; Musenero, Monica; Zhu, Bao-Ping; Nanyunja, Miriam

2017-06-01

AbstractPodoconiosis, a noninfectious elephantiasis, is a disabling neglected tropical disease. In August 2015, an elephantiasis case-cluster was reported in Kamwenge District, western Uganda. We investigated to identify the disease's nature and risk factors. We defined a suspected podoconiosis case as onset in a Kamwenge resident of bilateral asymmetrical lower limb swelling lasting ≥ 1 month, plus ≥ 1 of the following associated symptoms: skin itching, burning sensation, plantar edema, lymph ooze, prominent skin markings, rigid toes, or mossy papillomata. A probable case was a suspected case with negative microfilaria antigen immunochromatographic card test (ruling out filarial elephantiasis). We conducted active case-finding. In a case-control investigation, we tested the hypothesis that the disease was caused by prolonged foot skin exposure to irritant soils, using 40 probable case-persons and 80 asymptomatic village control-persons, individually matched by age and sex. We collected soil samples to characterize irritants. We identified 52 suspected (including 40 probable) cases with onset from 1980 to 2015. Prevalence rates increased with age; annual incidence (by reported onset of disease) was stable over time at 2.9/100,000. We found that 93% (37/40) of cases and 68% (54/80) of controls never wore shoes at work (Mantel-Haenszel odds ratio [OR MH ] = 7.7; 95% [confidence interval] CI = 2.0-30); 80% (32/40) of cases and 49% (39/80) of controls never wore shoes at home (OR MH = 5.2; 95% CI = 1.8-15); and 70% (27/39) of cases and 44% (35/79) of controls washed feet at day end (versus immediately after work) (OR = 11; 95% CI = 2.1-56). Soil samples were characterized as rich black-red volcanic clays. In conclusion, this reported elephantiasis is podoconiosis associated with prolonged foot exposure to volcanic soil. We recommended foot hygiene and universal use of protective shoes.

A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes.

PubMed

Hanson, Robert L; Muller, Yunhua L; Kobes, Sayuko; Guo, Tingwei; Bian, Li; Ossowski, Victoria; Wiedrich, Kim; Sutherland, Jeffrey; Wiedrich, Christopher; Mahkee, Darin; Huang, Ke; Abdussamad, Maryam; Traurig, Michael; Weil, E Jennifer; Nelson, Robert G; Bennett, Peter H; Knowler, William C; Bogardus, Clifton; Baier, Leslie J

2014-01-01

Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10(-8), which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.

Validity and power of association testing in family-based sampling designs: evidence for and against the common wisdom.

PubMed

Knight, Stacey; Camp, Nicola J

2011-04-01

Current common wisdom posits that association analyses using family-based designs have inflated type 1 error rates (if relationships are ignored) and independent controls are more powerful than familial controls. We explore these suppositions. We show theoretically that family-based designs can have deflated type-error rates. Through simulation, we examine the validity and power of family designs for several scenarios: cases from randomly or selectively ascertained pedigrees; and familial or independent controls. Family structures considered are as follows: sibships, nuclear families, moderate-sized and extended pedigrees. Three methods were considered with the χ(2) test for trend: variance correction (VC), weighted (weights assigned to account for genetic similarity), and naïve (ignoring relatedness) as well as the Modified Quasi-likelihood Score (MQLS) test. Selectively ascertained pedigrees had similar levels of disease enrichment; random ascertainment had no such restriction. Data for 1,000 cases and 1,000 controls were created under the null and alternate models. The VC and MQLS methods were always valid. The naïve method was anti-conservative if independent controls were used and valid or conservative in designs with familial controls. The weighted association method was generally valid for independent controls, and was conservative for familial controls. With regard to power, independent controls were more powerful for small-to-moderate selectively ascertained pedigrees, but familial and independent controls were equivalent in the extended pedigrees and familial controls were consistently more powerful for all randomly ascertained pedigrees. These results suggest a more complex situation than previously assumed, which has important implications for study design and analysis. © 2011 Wiley-Liss, Inc.

Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

PubMed

Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B; Graff-Radford, Neill R; Evans, Denis; De Jager, Philip L; Crane, Paul K; Buxbaum, Joseph D; Murrell, Jill R; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T; Green, Robert C; Barnes, Lisa L; Cantwell, Laura B; Fallin, M Daniele; Go, Rodney C P; Griffith, Patrick; Obisesan, Thomas O; Manly, Jennifer J; Lunetta, Kathryn L; Kamboh, M Ilyas; Lopez, Oscar L; Bennett, David A; Hendrie, Hugh; Hall, Kathleen S; Goate, Alison M; Byrd, Goldie S; Kukull, Walter A; Foroud, Tatiana M; Haines, Jonathan L; Farrer, Lindsay A; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Mayeux, Richard

2013-04-10

Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. To identify genetic loci associated with late-onset Alzheimer disease in African Americans. The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Presence of Alzheimer disease according to standardized criteria. Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 < D' < 0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ϵ4-determining SNP rs429358 (allele = C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P = 5.5 × 10(-47)). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005 < empirical P < .001). In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.

Association between enteropathogens and malnutrition in children aged 6-23 mo in Bangladesh: a case-control study.

PubMed

Platts-Mills, James A; Taniuchi, Mami; Uddin, Md Jashim; Sobuz, Shihab Uddin; Mahfuz, Mustafa; Gaffar, Sm Abdul; Mondal, Dinesh; Hossain, Md Iqbal; Islam, M Munirul; Ahmed, Am Shamsir; Petri, William A; Haque, Rashidul; Houpt, Eric R; Ahmed, Tahmeed

2017-05-01

Background: Early exposure to enteropathogens has been associated with malnutrition in children in low-resource settings. However, the contribution of individual enteropathogens remains poorly defined. Molecular diagnostics offer an increase in sensitivity for detecting enteropathogens but have not been comprehensively applied to studies of malnutrition. Objective: We sought to identify enteropathogens associated with malnutrition in Bangladesh. Design: Malnourished children [weight-for-age z score (WAZ) <-2] aged 6-23 mo in Dhaka, Bangladesh, and identified by active community surveillance were enrolled as cases, and normal-weight children (WAZ >-1) of the same age and from the same community were enrolled as controls. Stools were collected at enrollment and, for cases, after a 5-mo nutritional intervention. Enrollment and follow-up stools were tested by quantitative polymerase chain reaction for 32 enteropathogens with the use of a custom-developed TaqMan Array Card. Results: Enteropathogen testing was performed on 486 cases and 442 controls upon enrollment and 365 cases at follow-up. At enrollment, the detection of enteroaggregative Escherichia coli (OR: 1.39; 95% CI: 1.05, 1.83), Campylobacter spp. (OR: 1.46; 95% CI: 1.11, 1.91), heat-labile enterotoxin-producing E. coli (OR: 1.55; 95% CI: 1.04, 2.33), Shigella /enteroinvasive E. coli (OR: 1.65; 95% CI: 1.10, 2.46), norovirus genogroup I (OR: 1.66; 95% CI: 1.23, 2.25), and Giardia (OR: 1.73; 95% CI: 1.20, 2.49) were associated with malnourished cases, and the total burden of these pathogens remained associated with malnutrition after adjusting for sociodemographic factors. The number of these pathogens at follow-up was negatively associated with the change in WAZ during the intervention (-0.10 change in WAZ per pathogen detected; 95% CI: -0.14, -0.06), whereas the number at enrollment was positively associated with the change in WAZ (0.05 change in WAZ per pathogen detected; 95% CI: 0.00, 0.10). Conclusions: A subset of enteropathogens was associated with malnutrition in this setting. Broad interventions designed to reduce the burden of infection with these pathogens are needed. This trial was registered at clinicaltrials.gov as NCT02441426.

Pregnancy outcomes of women with failure to retain rubella immunity.

PubMed

Schwartzenburg, Christopher J; Gilmandyar, Dzhamala; Thornburg, Loralei L; Hackney, David N

2014-12-01

We sought to explore the clinical variables associated with the loss of rubella immunity during pregnancy and to determine if these changes are linked to obstetrical complications. This is a case-control study in which women were identified whose rubella antibody titers were equivocal or non-immune and compared to those who had retained immunity. Two hundred and eighty-five cases were identified and compared to the same number of controls using Student's t test, Mann-Whitney U-test or Fisher's exact test. Univariate and multivariate logistic regressions were employed. Subjects with diminished immunity were more likely to have public insurance and higher gravidity with a trend toward increased tobacco use. Diminished rubella immunity was not associated with adverse obstetrical outcomes, including preterm birth and pre-eclampsia and is likely not a risk factor for these pregnancy outcomes. While no adverse pregnancy outcomes were associated with a loss of rubella immunity, women with greater number of pregnancies appear to lose their immunity to rubella. This relationship needs to be explored further and if proven, revaccination prior to pregnancy may need to be addressed.

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study.

PubMed

Schmidt, Axel J; Rockstroh, Jürgen K; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

2011-03-08

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.

Socioeconomic Status and Childhood Cancer Incidence: A Population-Based Multilevel Analysis.

PubMed

Kehm, Rebecca D; Spector, Logan G; Poynter, Jenny N; Vock, David M; Osypuk, Theresa L

2018-05-01

The etiology of childhood cancers remains largely unknown, especially regarding environmental and behavioral risk factors. Unpacking the association between socioeconomic status (SES) and incidence may offer insight into such etiology. We tested associations between SES and childhood cancer incidence in a population-based case-cohort study (source cohort: Minnesota birth registry, 1989-2014). Cases, ages 0-14 years, were linked from the Minnesota Cancer Surveillance System to birth records through probabilistic record linkage. Controls were 4:1 frequency matched on birth year (2,947 cases and 11,907 controls). We tested associations of individual-level (maternal education) and neighborhood-level (census tract composite index) SES using logistic mixed models. In crude models, maternal education was positively associated with incidence of acute lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI): 1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and neuroblastoma (OR = 1.15, 95% CI: 1.02, 1.30). Adjustment for established risk factors-including race/ethnicity, maternal age, and birth weight-substantially attenuated these positive associations. Similar patterns were observed for neighborhood-level SES. Conversely, higher maternal education was inversely associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51, 0.98). Overall, beyond the social patterning of established demographic and pregnancy-related exposures, SES is not strongly associated with childhood cancer incidence.

The association between reflux esophagitis and airway hyper-reactivity in patients with gastro-esophageal reflux

PubMed Central

Karbasi, Ashraf; Ardestani, Mohammad Emami; Ghanei, Mostafa; Harandi, Ali Amini

2013-01-01

Background: The association of gastro-esophageal reflux (GER) with a wide variety of pulmonary disorders was recognized. We aimed to evaluate the effect of GER-induced esophagitis on airway hyper-reactivity (AHR) in patients and the response to treatment. Materials and Methods: In this cohort study, 30 patients attending the gastrointestinal clinic of a university hospital with acid reflux symptoms were included. All patients were evaluated endoscopically and divided into case group with esophagitis and control group without any evidence of esophagitis. Spirometry and methacholine test were done in all patients before and after treatment of GER with pantoprazole 40 mg daily for six months. Results: There was a significant difference in the rate of positive methacholine test between the cases (40%) and the controls (6.7%) prior to anti-acid therapy (P < 0.0001). After six months of treatment, the frequency of positive methacholine test diminished from 40 to 13.3% in the case group (P < 0.05) but did not change in the controls (P = 0.15). Conclusion: The presence of esophagitis due to GER would increase the AHR and treatment with pantoperazole would decrease AHR in patients with proved esophagitis and no previous history of asthma after six months. PMID:24250694

Mitochondrial DNA variants in obesity.

PubMed

Knoll, Nadja; Jarick, Ivonne; Volckmar, Anna-Lena; Klingenspor, Martin; Illig, Thomas; Grallert, Harald; Gieger, Christian; Wichmann, Heinz-Erich; Peters, Annette; Wiegand, Susanna; Biebermann, Heike; Fischer-Posovszky, Pamela; Wabitsch, Martin; Völzke, Henry; Nauck, Matthias; Teumer, Alexander; Rosskopf, Dieter; Rimmbach, Christian; Schreiber, Stefan; Jacobs, Gunnar; Lieb, Wolfgang; Franke, Andre; Hebebrand, Johannes; Hinney, Anke

2014-01-01

Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n = 1,697 obese cases (BMI ≥ 30 kg/m2) and n = 2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p = 0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p = 0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p = 0.007, m.16189T/C, p = 0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their offspring could not be substantiated by the findings of the present study.

Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.

PubMed

Wang, S; Wang, J; Fan, M-J; Li, T-Y; Pan, H; Wang, X; Liu, H-K; Lin, Q-F; Zhang, J-G; Guan, L-P; Zhernakova, D V; O'Brien, S J; Feng, Z-R; Chang, L; Dai, E-H; Lu, J-H; Xi, H-L; Zeng, Z; Yu, Y-Y; Wang, B-B

2018-03-27

The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population. © 2018 John Wiley & Sons Ltd.

Association between resilience and posttraumatic stress disorder among Brazilian victims of urban violence: a cross-sectional case-control study.

PubMed

Teche, Stefania Pigatto; Barros, Alcina Juliana Soares; Rosa, Regis Goulart; Guimarães, Luciano Pinto; Cordini, Kariny Larissa; Goi, Julia Domingues; Hauck, Simone; Freitas, Lucia Helena

2017-01-01

This study investigated the association between resilience and posttraumatic stress disorder (PTSD) among Brazilian victims of urban violence. It also compared defense mechanisms, parental bonding, and childhood trauma between those who developed PTSD and those who did not. This cross-sectional case-control study included 66 adult subjects exposed to recent urban violence in southern Brazil - 33 with PTSD and 33 healthy controls matched by sex and age - who were administered the Resilience Scale, Defense Style Questionnaire, Parental Bonding Instrument, and Childhood Trauma Questionnaire. The statistical tests used were the McNemar test for categorical variables, the Wilcoxon signed-rank test for continuous asymmetric variables, and the paired Student t-test for continuous symmetric variables. The PTSD group showed lower total Resilience Scale scores compared with controls (128.4±20.7 vs. 145.8±13.1, respectively; p = 0.01), along with a lower ability to solve situations and lower personal values that give meaning to life (p = 0.019). They also had lower rates of mature defense mechanisms (p < 0.001) and higher rates of emotional (p = 0.001) and physical (p = 0.003) abuse during childhood. Lower levels of resilience, especially the ability to solve situations and having personal values that give meaning to life, immature defense mechanisms, and emotional and physical abuse in childhood are associated with PTSD in adult Brazilian victims of urban violence.

Association of Interleukin 23 Receptor Polymorphisms with Anti-Topoisomerase-I Positivity and Pulmonary Hypertension in Systemic Sclerosis

PubMed Central

AGARWAL, SANDEEP K.; GOURH, PRAVITT; SHETE, SANJAY; PAZ, GENE; DIVECHA, DIPAL; REVEILLE, JOHN D.; ASSASSI, SHERVIN; TAN, FILEMON K.; MAYES, MAUREEN D.; ARNETT, FRANK C.

2010-01-01

Objective IL23R has been identified as a susceptibility gene for development of multiple autoimmune diseases. We investigated the possible association of IL23R with systemic sclerosis (SSc), an autoimmune disease that leads to the development of cutaneous and visceral fibrosis. Methods We tested 9 single-nucleotide polymorphisms (SNP) in IL23R for association with SSc in a cohort of 1402 SSc cases and 1038 controls. IL23R SNP tested were previously identified as SNP showing associations with inflammatory bowel disease. Results Case-control comparisons revealed no statistically significant differences between patients and healthy controls with any of the IL23R polymorphisms. Analyses of subsets of SSc patients showed that rs11209026 (Arg381Gln variant) was associated with anti-topoisomerase I antibody (ATA)-positive SSc (p = 0.001)) and rs11465804 SNP was associated with diffuse and ATA-positive SSc (p = 0.0001, p = 0.0026, respectively). These associations remained significant after accounting for multiple comparisons using the false discovery rate method. Wild-type genotype at both rs11209026 and rs11465804 showed significant protection against the presence of pulmonary hypertension (PHT). (p = 3×10−5, p = 1×10−5, respectively). Conclusion Polymorphisms in IL23R are associated with susceptibility to ATA-positive SSc and protective against development of PHT in patients with SSc. PMID:19918037

Influence of individual differences in disease perception on consumer response to direct-to-consumer genomic testing

PubMed Central

Boeldt, D.L.; Schork, N.J.; Topol, E.J.; Bloss, C.S.

2016-01-01

Individuals who undergo multiplex direct-to-consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow-up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer’s disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services. PMID:24798746

Influence of individual differences in disease perception on consumer response to direct-to-consumer genomic testing.

PubMed

Boeldt, D L; Schork, N J; Topol, E J; Bloss, C S

2015-03-01

Individuals who undergo multiplex direct-to-consumer (DTC) genomic testing receive genetic risk results for multiple conditions. To date, research has not investigated the influence of individual differences in disease perceptions among consumers on testing outcomes. A total of 2037 participants received DTC genomic testing and completed baseline and follow-up surveys assessing disease perceptions and health behaviors. Participants were asked to indicate their most feared disease of those tested. Perceived seriousness and controllability of the disease via lifestyle or medical intervention were assessed. Participants most frequently reported heart attack (19.1%) and Alzheimer's disease (18.6%) as their most feared disease. Perceived seriousness and control over the feared disease both influenced response to DTC genomic testing. Greater perceived seriousness and diminished perceived control were associated with higher, but not clinically significant levels of anxiety and distress. In some cases these associations were modified by genetic risk. No significant associations were observed for diet, exercise and screening behaviors. Individual differences in disease perceptions influence psychological outcomes following DTC genomic testing. Higher perceived seriousness may make a consumer more psychologically sensitive to test results and greater perceived control may protect against adverse psychological outcomes. Findings may inform development of educational and counseling services. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors associated with adult poisoning in northern Malaysia: a case-control study.

PubMed

Fathelrahman, A I; Ab Rahman, A F; Zain, Z Mohd; Tengku, M A

2006-04-01

Data on adult risk factors associated with drug or chemical poisonings in Malaysia are scarce. The objective of the study was to identify possible risk factors associated with adult admissions to the Penang General Hospital (PGH) due to chemical poisoning and/or drug overdose. The present study was a case-control study, conducted over 18 weeks. One hundred acutely poisoned adult patients admitted to PGH during the period from September 2003 to February 2004 were considered as cases. Two hundred patients admitted to the same medical wards for other illnesses, during the same period, were matched for age and gender with the poisoned cases and thus selected as controls. McNemar test and binary logistic were used for univariate analysis and logistic regression analysis for multivariate analyses. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for each predictor variable. Positive histories of psychiatric illness and previous poisoning, problems in boy/girl friend relationships, family problems, marital problems, Indian ethnicity, Chinese ethnicity, living in rented houses and living in a household with less than five people were significant risk factors associated with adult admissions due to poisoning.

Association between autism and variants in the wingless-type MMTV integration site family member 2 ( WNT2) gene.

PubMed

Marui, Tetsuya; Funatogawa, Ikuko; Koishi, Shinko; Yamamoto, Kenji; Matsumoto, Hideo; Hashimoto, Ohiko; Jinde, Seiichiro; Nishida, Hisami; Sugiyama, Toshiro; Kasai, Kiyoto; Watanabe, Keiichiro; Kano, Yukiko; Kato, Nobumasa

2010-05-01

Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time. We conducted a case-control study of nine single nucleotide polymorphisms (SNPs) within the WNT2 gene in 170 patients with autism and 214 normal controls in a Japanese population. We then conducted a TDT analysis in 98 autistic families (trios) to replicate the results of the case-control study. In the case-control study, three SNPs (rs3779547, rs4727847 and rs3729629), two major individual haplotypes (A-T-C and G-G-G, consisting of rs3779547, rs4727847, and rs3729629), and global probability values of the haplotype distributions in the same region (global p=0.0091) showed significant associations with autism. Furthermore, all of these significant associations were also observed in the TDT analysis. Our findings provide evidence for a significant association between WNT2 and autism. Considering the important role of the WNT2 gene in brain development, our results therefore indicate that the WNT2 gene is one of the strong candidate genes for autism.

Seizures in the elderly: Impact on mental status, mood and sleep

PubMed Central

Haut, Sheryl R.; Katz, Mindy; Masur, Jonathan; Lipton, Richard B.

2009-01-01

Co-morbidities of epilepsy have not been well explored in the elderly. Herein, we examined mental status, mood, and sleep in elderly patients with epilepsy, compared to age and gender matched community controls without epilepsy from the Einstein Aging Study. Testing included a mental status test, the Blessed Information Memory and Concentration (BIMC) test; Prime-MD Patient Health Questionnaire (PHQ) Depression and Anxiety Modules; and Medical Outcomes Study Sleep Scale. Persons with epilepsy (n=31) had higher mean BIMC scores than controls (n=31, BIMC 6.3 vs.1.2; p<0.0001). Mean PHQ Depression scores were higher for cases than controls indicating more depressive symptoms (4.2 vs. 0.8; p=0.006); six cases (18%) and no controls met screening criteria for depression. Mean PHQ Anxiety scores were also higher for cases than controls (3.7 vs. 0.0; p=0.001). Cases demonstrated poorer sleep scores in the categories of somnolence (p=0.009) and shortness of breath/headache (p=0.021). Thus, co-morbidities of epilepsy in this elderly population included decreased mental status, a higher prevalence of depression and anxiety, and poorer sleep health when compared to age mates without epilepsy. Mental status impairment was not related to anti-epileptic medication or mood disturbance. Further investigation will explore these associations prospectively. PMID:19189862

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

PubMed

van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

2016-07-14

Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Factors associated with voice disorders among teachers: a case-control study.

PubMed

Giannini, Susana Pimentel Pinto; Latorre, Maria do Rosário Dias de Oliveira; Ferreira, Léslie Piccolotto

2013-01-01

We aimed at verifying an association between voice disorders/stress and loss of work ability among female teachers who work in São Paulo's public school system. This is a paired case- control study. The case group was composed offiteachers with alterations in speech and larynges assessments, and the control group was formed by teachers without alterations in these evaluations who work in the same schools. Both groups answered the following questionnaires: Conditions of Vocal Production-Teachers, Job Stress Scale, and Work Ability Index. The analysis was performed using the chi-square association test and logistic regression models with the purpose of estimating the association between independent variables and voice disorders. We found differences between the groups in relation to stress in the workplace under high demand, a situation that poses greater risks of adverse reactions to the workers' physical and mental health. Regarding the ability to work, the categories poor and moderate ability for work are associated with voice disorders, regardless of job stress factors, age, and the unsatisfactory acoustic properties of the classrooms. This study confirmed the association between voice disorders and job stress, as well as between voice disorders and loss of work ability.

Household contact with pets and birds and risk of lymphoma.

PubMed

Bellizzi, Saverio; Cocco, Pierluigi; Zucca, Mariagrazia; D'Andrea, Ileana; Sesler, Simonetta; Monne, Maria; Onida, Angela; Piras, Giovanna; Uras, Antonella; Angelucci, Emanuele; Gabbas, Attilio; Rais, Marco; Nitsch, Dorothea; Ennas, Maria G

2011-02-01

Contact with household pets has been suggested to be inversely associated with lymphoma risk. We tested the hypothesis in a case-control study of lymphoma in the Sardinia region of Italy. Cases were 326 patients, first diagnosed with lymphoma in 1999-2003. Controls were 464 population controls, frequency matched to cases by age, gender, and area of residence. In person interviews included self-reported household contact with pets and birds, type of pet(s), and age at starting contact. Frequent contact with birds was inversely associated with lymphoma, and particularly B-cell non-Hodgkin lymphoma (odds ratio [OR] = 0.6, 95% confidence interval [95% CI]: 0.4, 0.9). Contact with chickens accounted for this inverse association, which was strongest for first contact occurring at age ≤8 years (OR = 0.4, 95% CI: 0.2, 1.0). No association was observed when first contact occurred at age 9 or older. Contact with any pets was inversely associated with risk of diffuse large B-cell lymphoma (OR = 0.4, 95% CI: 0.2, 1.0), but not other lymphoma subtypes. Our results support the hypothesis that early-life exposure to pets, birds and particularly with chickens might be associated with a reduced risk of lymphoma.

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel.

PubMed

Fernandez-Rozadilla, Ceres; Kartsonaki, Christiana; Woolley, Connor; McClellan, Michael; Whittington, Deb; Horgan, Gareth; Leedham, Simon; Kriaucionis, Skirmantas; East, James; Tomlinson, Ian

2018-03-06

Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.

PubMed

Dicks, Ed; Song, Honglin; Ramus, Susan J; Oudenhove, Elke Van; Tyrer, Jonathan P; Intermaggio, Maria P; Kar, Siddhartha; Harrington, Patricia; Bowtell, David D; Group, Aocs Study; Cicek, Mine S; Cunningham, Julie M; Fridley, Brooke L; Alsop, Jennifer; Jimenez-Linan, Mercedes; Piskorz, Anna; Goranova, Teodora; Kent, Emma; Siddiqui, Nadeem; Paul, James; Crawford, Robin; Poblete, Samantha; Lele, Shashi; Sucheston-Campbell, Lara; Moysich, Kirsten B; Sieh, Weiva; McGuire, Valerie; Lester, Jenny; Odunsi, Kunle; Whittemore, Alice S; Bogdanova, Natalia; Dürst, Matthias; Hillemanns, Peter; Karlan, Beth Y; Gentry-Maharaj, Aleksandra; Menon, Usha; Tischkowitz, Marc; Levine, Douglas; Brenton, James D; Dörk, Thilo; Goode, Ellen L; Gayther, Simon A; Pharoah, D P Paul

2017-08-01

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10 -3 ). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2 , where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P=0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P=0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P=0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality.

Investigation of a national outbreak of STEC Escherichia coli O157 using online consumer panel control methods: Great Britain, October 2014.

PubMed

Sinclair, C; Jenkins, C; Warburton, F; Adak, G K; Harris, J P

2017-04-01

In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2-92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0-157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.

Effectiveness of rotavirus pentavalent vaccine under a universal immunization programme in Israel, 2011-2015: a case-control study.

PubMed

Muhsen, K; Anis, E; Rubinstein, U; Kassem, E; Goren, S; Shulman, L M; Ephros, M; Cohen, D

2018-01-01

The use of rotavirus pentavalent vaccine (RotaTeq ® ) as a sole vaccine within rotavirus universal immunization programmes remains limited. We examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis (RVGE) hospitalization in Israel, after the introduction of universal immunization against the disease. A test-negative case-control study included age-eligible children for universal RotaTeq immunization (aged 2-59 months, born in 2011-2015). Cases (n = 98) were patients who tested positive for rotavirus by immunochromatography; those who tested negative (n = 628) comprised the control group. Information on rotavirus immunization history was obtained through linkage with a national immunization registry. Vaccination status was compared between cases and controls, adjusted odds ratios (aORs) were obtained from logistic regression models, and vaccine effectiveness calculated as (1 - aOR)*100. Immunization with RotaTeq was less frequent in RVGE cases (73.5%) than in controls (90.1%), p < 0.001; this association persisted after controlling for potential confounders. Effectiveness of the complete vaccine series was estimated at 77% (95% confidence interval (CI): 49-90) in children aged 6-59 months, and 86% (95% CI: 65-94) in children aged 6-23 months; whereas for the incomplete series, the respective estimates were 72% (95% CI: 28-89) and 75% (95% CI: 30-91). Vaccine effectiveness was estimated at 79% (95% CI: 45-92) against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11-89) against other genotype-RVGE hospitalizations. High effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country. Although partial vaccination conferred protection, completing the vaccine series is warranted to maximize the benefit. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture

PubMed Central

Hwang, Joo-Yeon; Lee, Seung Hun; Go, Min Jin; Kim, Beom-Jun; Kou, Ikuyo; Ikegawa, Shiro; Guo, Yan; Deng, Hong-Wen; Raychaudhuri, Soumya; Kim, Young Jin; Oh, Ji Hee; Kim, Youngdoe; Moon, Sanghoon; Kim, Dong-Joon; Koo, Heejo; Cha, My-Jung; Lee, Min Hye; Yun, Ji Young; Yoo, Hye-Sook; Kang, Young-Ah; Cho, Eun-Hee; Kim, Sang-Wook; Oh, Ki Won; Kang, Moo II; Son, Ho Young; Kim, Shin-Yoon; Kim, Ghi Su; Han, Bok-Ghee; Cho, Yoon Shin; Cho, Myeong-Chan; Lee, Jong-Young; Koh, Jung-Min

2014-01-01

Background Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10−8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions Our findings provide new insights into the genetic architecture underlying OF in East Asians. PMID:23349225

Do non-communicable diseases such as hypertension and diabetes associate with primary open-angle glaucoma? Insights from a case-control study in Nepal.

PubMed

Shakya-Vaidya, Suraj; Aryal, Umesh Raj; Upadhyay, Madan; Krettek, Alexandra

2013-11-04

Non-communicable diseases (NCDs) such as hypertension and diabetes are rapidly emerging public health problems worldwide, and they associate with primary open-angle glaucoma (POAG). POAG is the most common cause of irreversible blindness. The most effective ways to prevent glaucoma blindness involve identifying high-risk populations and conducting routine screening for early case detection. This study investigated whether POAG associates with hypertension and diabetes in a Nepalese population. To explore the history of systemic illness, our hospital-based case-control study used non-random consecutive sampling in the general eye clinics in three hospitals across Nepal to enroll patients newly diagnosed with POAG and controls without POAG. The study protocol included history taking, ocular examination, and interviews with 173 POAG cases and 510 controls. Data analysis comprised descriptive and inferential statistics. Descriptive statistics computed the percentage, mean, and standard deviation (SD); inferential statistics used McNemar's test to measure associations between diseases. POAG affected males more frequently than females. The odds of members of the Gurung ethnic group having POAG were 2.05 times higher than for other ethnic groups. Hypertension and diabetes were strongly associated with POAG. The overall odds of POAG increased 2.72-fold among hypertensive and 3.50-fold among diabetic patients. POAG associates significantly with hypertension and diabetes in Nepal. Thus, periodic glaucoma screening for hypertension and diabetes patients in addition to opportunistic screening at eye clinics may aid in detecting more POAG cases at an early stage and hence in reducing avoidable blindness.

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing

PubMed Central

Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Glendon, Gord; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hart, Steven N; Hartman, Mikael; Hooning, Maartje J; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; James, Paul A; John, Esther M; Johnson, Nichola; Jones, Michael; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lambrechts, Diether; Li, Na; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Meindl, Alfons; Mitchell, Gillian; Muir, Kenneth; Nevelsteen, Ines; van den Ouweland, Ans; Peterlongo, Paolo; Phuah, Sze Yee; Pylkäs, Katri; Rowley, Simone M; Sangrajrang, Suleeporn; Schmutzler, Rita K; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Verhoef, Senno; Wong-Brown, Michelle; Zheng, Wei; Zheng, Ying; Nevanlinna, Heli; Scott, Rodney J; Andrulis, Irene L; Wu, Anna H; Hopper, John L; Couch, Fergus J; Winqvist, Robert; Burwinkel, Barbara; Sawyer, Elinor J; Schmidt, Marjanka K; Rudolph, Anja; Dörk, Thilo; Brauch, Hiltrud; Hamann, Ute; Neuhausen, Susan L; Milne, Roger L; Fletcher, Olivia; Pharoah, Paul D P; Campbell, Ian G; Dunning, Alison M; Le Calvez-Kelm, Florence; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia

2016-01-01

Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. PMID:26921362

Polygenic interactions with environmental adversity in the aetiology of major depressive disorder.

PubMed

Mullins, N; Power, R A; Fisher, H L; Hanscombe, K B; Euesden, J; Iniesta, R; Levinson, D F; Weissman, M M; Potash, J B; Shi, J; Uher, R; Cohen-Woods, S; Rivera, M; Jones, L; Jones, I; Craddock, N; Owen, M J; Korszun, A; Craig, I W; Farmer, A E; McGuffin, P; Breen, G; Lewis, C M

2016-03-01

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene-environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10(-6)). SLEs and CT were also associated with MDD status (p = 2.19 × 10(-4) and p = 5.12 × 10(-20), respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene-environment interactions in complex traits.

Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece).

PubMed

Kokouva, Maria; Bitsolas, Nikolaos; Hadjigeorgiou, Georgios M; Rachiotis, George; Papadoulis, Nikolaos; Hadjichristodoulou, Christos

2011-01-04

The causality of lymphohaematopoietic cancers (LHC) is multifactorial and studies investigating the association between chemical exposure and LHC have produced variable results. The aim of this study was to investigate the relationships between exposure to pesticides and LHC in an agricultural region of Greece. A structured questionnaire was employed in a hospital-based case control study to gather information on demographics, occupation, exposure to pesticides, agricultural practices, family and medical history and smoking. To control for confounders, backward conditional and multinomial logistic regression analyses were used. To assess the dose-response relationship between exposure and disease, the chi-square test for trend was used. Three hundred and fifty-four (354) histologically confirmed LHC cases diagnosed from 2004 to 2006 and 455 sex- and age-matched controls were included in the study. Pesticide exposure was associated with total LHC cases (OR 1.46, 95% CI 1.05-2.04), myelodysplastic syndrome (MDS) (OR 1.87, 95% CI 1.00-3.51) and leukaemia (OR 2.14, 95% CI 1.09-4.20). A dose-response pattern was observed for total LHC cases (P = 0.004), MDS (P = 0.024) and leukaemia (P = 0.002). Pesticide exposure was independently associated with total LHC cases (OR 1.41, 95% CI 1.00 - 2.00) and leukaemia (OR 2.05, 95% CI 1.02-4.12) after controlling for age, smoking and family history (cancers, LHC and immunological disorders). Smoking during application of pesticides was strongly associated with total LHC cases (OR 3.29, 95% CI 1.81-5.98), MDS (OR 3.67, 95% CI 1.18-12.11), leukaemia (OR 10.15, 95% CI 2.15-65.69) and lymphoma (OR 2.72, 95% CI 1.02-8.00). This association was even stronger for total LHC cases (OR 18.18, 95% CI 2.38-381.17) when eating simultaneously with pesticide application. Lymphohaematopoietic cancers were associated with pesticide exposure after controlling for confounders. Smoking and eating during pesticide application were identified as modifying factors increasing the risk for LHC. The poor pesticide work practices identified during this study underline the need for educational campaigns for farmers.

Protecting health care workers from tuberculosis: a 10-year experience.

PubMed

Welbel, Sharon F; French, Audrey L; Bush, Patricia; DeGuzman, Delia; Weinstein, Robert A

2009-10-01

Cook County Hospital (CCH) is an inner-city, large public hospital. Twenty-five percent of Chicago's tuberculosis (TB) cases are diagnosed at CCH. We wanted to review and analyze interventions implemented over a 10-year period at CCH to prevent TB infection in health care workers. We performed a retrospective review of interventions to prevent health care-associated tuberculosis. We collated and analyzed tuberculin skin test conversions in our employees for the same time period. From 1990 to 2002, we cared for over 1800 in-patients with tuberculosis. During 1992-1997, multiple interventions to eliminate health care-associated spread of tuberculosis were implemented. Tuberculin skin test conversions in our employees decreased markedly from January 1994 through December 2002. Two drops in tuberculin skin test conversion rates occurred: one after introduction of basic administrative and engineering controls and a second after we experienced a decrease in missed TB cases and the introduction of N-95 personal respirators with 1-time qualitative fit testing. Our annual health care worker skin test conversion rate fell significantly when our primary interventions were relatively simple administrative and engineering controls. Educating health care workers to promptly recognize patients with TB and placing exhaust fans to create negative-pressure respiratory isolation rooms were probably our 2 most potent infection control measures.

Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.

PubMed

Song, Minsun; Wheeler, William; Caporaso, Neil E; Landi, Maria Teresa; Chatterjee, Nilanjan

2018-03-01

Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large-scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta-analysis of "one-step" maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package. © 2017 WILEY PERIODICALS, INC.

Missed opportunities for HIV testing in health care settings among young African American men who have sex with men: implications for the HIV epidemic.

PubMed

Dorell, Christina G; Sutton, Madeline Y; Oster, Alexandra M; Hardnett, Felicia; Thomas, Peter E; Gaul, Zaneta J; Mena, Leandro A; Heffelfinger, James D

2011-11-01

Limited health care access and missed opportunities for HIV and other sexually transmitted infection (STI) education and testing in health care settings may contribute to risk of HIV infection. In 2008, we conducted a case-control study of African American men who have sex with men (MSM) in a southeastern city (Jackson, Mississippi) with an increase in numbers of newly reported HIV cases. Our aims were to evaluate associations between health care and HIV infection and to identify missed opportunities for HIV/STI testing. We queried 40 potential HIV-infected cases and 936 potential HIV-uninfected controls for participation in this study. Study enrollees included HIV-infected cases (n=30) and HIV-uninfected controls (n=95) who consented to participate and responded to a self-administered computerized survey about sexual risk behaviors and health care utilization. We used bivariate analysis and logistic regression to test for associations between potential risk factors and HIV infection. Cases were more likely than controls to lack health insurance (odds ratio [OR]=2.5; 95% confidence interval [CI]=1.1-5.7), lack a primary care provider (OR=6.3; CI=2.3-16.8), and to not have received advice about HIV or STI testing or prevention (OR=5.4; CI=1.3-21.5) or disclose their sexual identity (OR=7.0; CI=1.6-29.2) to a health care provider. In multivariate analysis, lacking a primary health care provider (adjusted odds ratio [AOR]=4.5; CI=1.4-14.7) and not disclosing sexual identity to a health care provider (AOR=8.6; CI=1.8-40.0) were independent risk factors for HIV infection among African American MSM. HIV prevention interventions for African American MSM should address access to primary health care providers for HIV/STI prevention and testing services and the need for increased discussions about sexual health, sexual identity, and sexual behaviors between providers and patients in an effort to reduce HIV incidence and HIV-related health disparities.

Molecular genetic studies in Saudi population; identified variants from GWAS and meta-analysis in stroke.

PubMed

Alharbi, Khalid Khalaf; Ali Khan, Imran; Alotaibi, Mohammad Abdullah; Saud Aloyaid, Abdullah; Al-Basheer, Haifa Abdulaziz; Alghamdi, Naelah Abdullah; Al-Baradie, Raid Saleem; Al-Sulaiman, A M

2018-01-01

Stroke is a multifactorial and heterogeneous disorder, correlates with heritability and considered as one of the major diseases. The prior reports performed the variable models such as genome-wide association studies (GWAS), replication, case-control, cross-sectional and meta-analysis studies and still, we lack diagnostic marker in the global world. There are limited studies were carried out in Saudi population, and we aim to investigate the molecular association of single nucleotide polymorphisms (SNPs) identified through GWAS and meta-analysis studies in stroke patients in the Saudi population. In this case-control study, we have opted gender equality of 207 cases and 207 controls from the capital city of Saudi Arabia in King Saud University Hospital. The peripheral blood (5 ml) sample will be collected in two different vacutainers, and three mL of the coagulated blood will be used for lipid analysis (biochemical tests) and two mL will be used for DNA analysis (molecular tests). Genomic DNA will be extracted with the collected blood samples, and specific primers will be designed for the opted SNPs ( SORT1 -rs646218 and OLR1 -rs11053646 polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be carried out to cross check the results. The rs646218 and rs11053646 polymorphisms were significantly associated with allele, genotype and dominant models with and without crude odds ratios (OR's) and Multiple logistic regression analysis (p < 0.05). Correlation between lipid profile and genotypes has confirmed the significant relation between triglycerides and rs646218 and rs1105364 6polymorphisms. However, rs11053646 polymorphism was correlated with HDLC (p = 0.04). Genotypes were examined in both males' vs. males and females' vs. females in cases and control and we concluded that in rs11053646 polymorphisms with male subjects compared between cases and controls found to be associated with dominant model heterozygote genotypes (p < 0.05). The results of the current study confirmed the SORT1 and OLR1  SNPs were associated in the Saudi population. The current results were in the association with the prior study results documented through GWAS and meta-analysis association. However, other ethnic population studies should be performed to rule out in the human hereditary diseases.

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population.

PubMed

Geng, Ting-Ting; Xun, Xiao-Jie; Li, Sen; Feng, Tian; Wang, Li-Ping; Jin, Tian-Bo; Hou, Peng

2015-06-14

To investigate the association between colorectal cancer (CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population. A case-control study was conducted including 360 esophageal cancer patients and 310 healthy controls. Thirty-one single-nucleotide polymorphisms (SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from Hardy-Weinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ(2) test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models (codominant, dominant, recessive, overdominant, and additive). ORs and 95%CIs were calculated by unconditional logistic regression with adjustments for age and sex. The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold (95%CI: 1.15-2.06; P = 0.004) and 1.28-fold (95%CI: 1.03-1.60; P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model (OR = 0.52, 95%CI: 0.31-0.88; P = 0.033) and recessive model (OR = 0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827 C/T-T/T genotype was associated with a 0.67-fold (95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition, rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold (95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model. These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.

Childhood exposure to infection and risk of adult onset wheeze and atopy.

PubMed

Bodner, C; Anderson, W J; Reid, T S; Godden, D J

2000-05-01

The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.

Environmental Exposures, Genetic Polymorphisms and p53 Mutational Spectra in a Case-Control Study of Breast Cancer

DTIC Science & Technology

1999-01-01

potential benefits of serotonin reuptake inhibitors in X1 tests were performed to evaluate associations of 5-HTT smoking cessation (15) suggested... dogs , sausages, bacon and cold diet assessment instrument used is a well-established tool for cuts was also assessed. A poultry index included...Controls were frequency-matched to cases on age and county. The listing of licensed New York State drivers was used for random selection of women

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

PubMed

Sýkora, Josef; Huml, Michal; Siala, Konrad; Pomahačová, Renáta; Jehlička, Petr; Liška, Jiří; Kuntscherová, Jana; Schwarz, Jan

2016-10-01

Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 μg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 μg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

Comparing Anxiety and Depression in Patients With Takotsubo Stress Cardiomyopathy to Those With Acute Coronary Syndrome.

PubMed

Goh, Anne C H; Wong, Stephanie; Zaroff, Jonathan G; Shafaee, Navid; Lundstrom, Robert J

2016-01-01

To determine whether anxiety or depression is associated with takotsubo stress cardiomyopathy (TSCM). A retrospective case-control study was conducted among 73 TSCM cases and 111 acute coronary syndrome (ACS) controls matched for age, sex, and cardiac catheterization date. The study was conducted between May 1, 2009, and February 28, 2010. The Hospital Anxiety and Depression Scale was completed by all participants after hospital discharge. The Hospital Anxiety and Depression Scale was used to assess psychological distress with measurement of anxiety and depression scores. The presence of a stressful emotional or physical trigger before the TSCM presentation was determined. Univariate testing was performed to quantify the associations between anxiety and depression and TSCM trigger status. Multivariable logistic regression was used to quantify the independent associations between anxiety and depression and TSCM status after controlling for relevant covariates. The mean anxiety score was 6.7 ± 4.7 for TSCM cases versus 5.4 ± 3.4 for ACS controls (P = .06). The mean depression score was 4.3 ± 3.7 for TSCM cases versus 4.0 ± 3.1 for controls (P = .61). Anxiety was particularly associated with TSCM status with an emotional trigger (P = .05). After multivariable adjustment, anxiety (OR = 1.13; 95% CI, 1.01-1.26; P = .03) was associated with TSCM status but depression was not (OR = 0.94; 95% CI, 0.83-1.05; P = .29). In comparison with a control group with ACS, patients who presented with TSCM have higher levels of anxiety but not depression.

Neospora caninum versus Brucella spp. exposure among dairy cattle in Ethiopia: a case control study.

PubMed

Asmare, Kassahun

2014-08-01

This case-control study aimed at assessing the relative association of Neospora caninum and Brucella species exposure with reproductive disorders. The study was carried out between October 2011 and June 2012 on 731 dairy cows sampled from 150 dairy farms in selected 17 conurbations of Ethiopia. Two hundred sixty-six of the cows were categorized as cases based on their history of abortion or stillbirth while the remaining 465 were controls. The presence of antibody to N. caninum was screened using indirect ELISA, while Brucella spp. exposure was assayed serially using Rose Bengal Plate Test and Complement Fixation Test. Exposure to N. caninum was more frequently observed among cases (23.8%) than controls (12.7%), while no significant difference (p > 0.05) was noted for Brucella exposure between the two groups. Moreover, the proportion of cows with disorders like retention of fetal membrane, endometritis and increased inter-calving period were significantly higher (p < 0.05) among Neospora seropositive cows. In conclusion, the finding discloses the strong association of N. caninum with reproductive disorders compared to Brucella spp. exposure. However, neither N. caninum nor Brucella spp. could explain the majority (73.2%) of the reported abortions and stillbirths in cattle. Hence, this observation underscores the need for more intensive investigation on the identification of causes of the aforementioned disorders in dairy cattle of Ethiopia.

Pain in adolescents and its risk factors: A case-control study.

PubMed

Agüero, Gonzalo; Salmain, Soledad; Manzur, Belén; Berner, Enrique

2018-04-01

The most common painful syndromes (headache, abdominal pain and musculoskeletal pain) develop or worsen during adolescence and are a common reason for consultation. Evaluate the association of age, sex, obesity, pubertal development, schooling level, employment and family structure with consultation for pain in adolescents. Case-control study conducted between February 1st, 2014 and June 30th, 2015. ages 10 to 20 years, both sexes, consultation for pain (cases), or a checkup and/or school physical (controls). χ 2 test and Student" s tests were used. Odds ratios (OR) were calculated. A binary logistic regression model was constructed to independently assess each pain-related variable. A total of 4224 medical records were evaluated; 237 cases and 468 controls were included. Adolescents with pain exhibited: greater age (p < 0.0001; OR 2.3; 95% CI: 1.63.2); greater number of females (p < 0.0001; OR 2.24; 95% CI: 1.61-3.12); greater pubertal development (p < 0.0035; OR 2.16; 95% CI: 1.33.6); greater school dropout level (p < 0.0001; OR 13.4; 95% CI: 3.9-42.9); greater employment levels (p < 0.0001; OR 3.04; 95% CI: 1.7-5.3). Only age, female sex and school dropout were independently associated with consultation for pain. There were no significant differences with obesity and family structure. Older age, female sex and school dropout were independent risk factors in consultation for pain in adolescents. Puberty and employment were associated, but were not found to be independent risk factors. Sociedad Argentina de Pediatría.

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap.

PubMed

Hinks, Anne; Cobb, Joanna; Sudman, Marc; Eyre, Stephen; Martin, Paul; Flynn, Edward; Packham, Jonathon; Barton, Anne; Worthington, Jane; Langefeld, Carl D; Glass, David N; Thompson, Susan D; Thomson, Wendy

2012-07-01

Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case-Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.

FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

PubMed Central

Agarwal, D; Pineda, S; Michailidou, K; Herranz, J; Pita, G; Moreno, L T; Alonso, M R; Dennis, J; Wang, Q; Bolla, M K; Meyer, K B; Menéndez-Rodríguez, P; Hardisson, D; Mendiola, M; González-Neira, A; Lindblom, A; Margolin, S; Swerdlow, A; Ashworth, A; Orr, N; Jones, M; Matsuo, K; Ito, H; Iwata, H; Kondo, N; Hartman, M; Hui, M; Lim, W Y; T-C Iau, P; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Kang, D; Choi, J-Y; Park, S K; Noh, D-Y; Hopper, J L; Schmidt, D F; Makalic, E; Southey, M C; Teo, S H; Yip, C H; Sivanandan, K; Tay, W-T; Brauch, H; Brüning, T; Hamann, U; Dunning, A M; Shah, M; Andrulis, I L; Knight, J A; Glendon, G; Tchatchou, S; Schmidt, M K; Broeks, A; Rosenberg, E H; van't Veer, L J; Fasching, P A; Renner, S P; Ekici, A B; Beckmann, M W; Shen, C-Y; Hsiung, C-N; Yu, J-C; Hou, M-F; Blot, W; Cai, Q; Wu, A H; Tseng, C-C; Van Den Berg, D; Stram, D O; Cox, A; Brock, I W; Reed, M W R; Muir, K; Lophatananon, A; Stewart-Brown, S; Siriwanarangsan, P; Zheng, W; Deming-Halverson, S; Shrubsole, M J; Long, J; Shu, X-O; Lu, W; Gao, Y-T; Zhang, B; Radice, P; Peterlongo, P; Manoukian, S; Mariette, F; Sangrajrang, S; McKay, J; Couch, F J; Toland, A E; Yannoukakos, D; Fletcher, O; Johnson, N; Silva, I dos Santos; Peto, J; Marme, F; Burwinkel, B; Guénel, P; Truong, T; Sanchez, M; Mulot, C; Bojesen, S E; Nordestgaard, B G; Flyer, H; Brenner, H; Dieffenbach, A K; Arndt, V; Stegmaier, C; Mannermaa, A; Kataja, V; Kosma, V-M; Hartikainen, J M; Lambrechts, D; Yesilyurt, B T; Floris, G; Leunen, K; Chang-Claude, J; Rudolph, A; Seibold, P; Flesch-Janys, D; Wang, X; Olson, J E; Vachon, C; Purrington, K; Giles, G G; Severi, G; Baglietto, L; Haiman, C A; Henderson, B E; Schumacher, F; Le Marchand, L; Simard, J; Dumont, M; Goldberg, M S; Labrèche, F; Winqvist, R; Pylkäs, K; Jukkola-Vuorinen, A; Grip, M; Devilee, P; Tollenaar, R A E M; Seynaeve, C; García-Closas, M; Chanock, S J; Lissowska, J; Figueroa, J D; Czene, K; Eriksson, M; Humphreys, K; Darabi, H; Hooning, M J; Kriege, M; Collée, J M; Tilanus-Linthorst, M; Li, J; Jakubowska, A; Lubinski, J; Jaworska-Bieniek, K; Durda, K; Nevanlinna, H; Muranen, T A; Aittomäki, K; Blomqvist, C; Bogdanova, N; Dörk, T; Hall, P; Chenevix-Trench, G; Easton, D F; Pharoah, P D P; Arias-Perez, J I; Zamora, P; Benítez, J; Milne, R L

2014-01-01

Background: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. Methods: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. Results: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. Conclusion: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2. PMID:24548884

The Relationship between Chlamydia trachomatis Genital Infection and Spontaneous Abortion.

PubMed

Ahmadi, Amjad; Khodabandehloo, Mazaher; Ramazanzadeh, Rashid; Farhadifar, Fariba; Roshani, Daem; Ghaderi, Ebrahim; Farhangi, Niloofar

2016-01-01

Chlamydia trachomatis is the etiology of most of sexually transmitted diseases. Colonization of C. trachomatis in the genital tract during early gestation has been associated with preterm birth, and preterm premature rupture of the membranes. The role of C. trachomatis on spontaneous abortion has not yet been proved completely. The aim of this study was to evaluate the frequency of C. trachomatis infection among pregnant women and its association with spontaneous abortion. This case-control study was conducted from August 2012 until January 2013. Totally, 218 women were included; 109 women with spontaneous abortion with gestation age between 10-20 weeks (cases), and 109 women with normal pregnancy with gestation age between 20-30 weeks (controls) in Sanandaj, Iran. DNA was extracted from endocervical swabs and a PCR test was conducted for detection of C. trachomatis infection in women using specific primers. Independent T-test and Chi-square were used for comparison of quantitative and qualitative variables, respectively, and p<0.05 was considered significant. The total prevalence of C. trachomatis infection was 38(17.43%) in endocervical swabs of women. However, the number of cases with C. trachomatis infections was 25 out of 109(22.9%) in the case group and 13 out of 109(11.9%) in control group, respectively. Association between chlamydia infection and spontaneous abortion was statistically significant (OR=2.198, CI 95%: 1.058-4.56). Our study showed that C. trachomatis infection was associated with spontaneous abortion. Thus, screening and treatment of pregnant women may prevent this adverse pregnancy outcome.

Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC.

PubMed

Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Bayés, Mònica; Cormand, Bru

2013-09-01

Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case-control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.

Integrated rare variant-based risk gene prioritization in disease case-control sequencing studies.

PubMed

Lin, Jhih-Rong; Zhang, Quanwei; Cai, Ying; Morrow, Bernice E; Zhang, Zhengdong D

2017-12-01

Rare variants of major effect play an important role in human complex diseases and can be discovered by sequencing-based genome-wide association studies. Here, we introduce an integrated approach that combines the rare variant association test with gene network and phenotype information to identify risk genes implicated by rare variants for human complex diseases. Our data integration method follows a 'discovery-driven' strategy without relying on prior knowledge about the disease and thus maintains the unbiased character of genome-wide association studies. Simulations reveal that our method can outperform a widely-used rare variant association test method by 2 to 3 times. In a case study of a small disease cohort, we uncovered putative risk genes and the corresponding rare variants that may act as genetic modifiers of congenital heart disease in 22q11.2 deletion syndrome patients. These variants were missed by a conventional approach that relied on the rare variant association test alone.

A polymorphism in the glucokinase gene that raises plasma fasting glucose, rs1799884, is associated with diabetes mellitus and prostate cancer: findings from a population-based, case-control study (the ProtecT study)

PubMed Central

Murad, Ali S; Smith, George Davey; Lewis, Sarah J; Cox, Angela; Donovan, Jenny L; Neal, David E; Hamdy, Freddie C; Martin, Richard M

2010-01-01

Epidemiological studies have identified a positive association between prostate cancer and recent onset type 2 diabetes mellitus but an increasingly inverse association with greater duration of type 2 diabetes. The mecha- nisms underlying these paradoxical associations are not clear. A single nucleotide polymorphism in the glucokinase gene, rs1799884, is associated with higher circulating plasma fasting glucose and with an increased risk of type 2 diabetes. We report a case-control study nested within the population-based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50-69 years based around 9 UK cities were invited for a prostate specific antigen (PSA) test between June 2002 and November 2006. 1,551 cases and 2,993 controls were geno-typed. We observed suggestive evidence for a positive association between the AA variant rs1799884 and PSA-detected prostate cancer (ORAA V GG= 1.40, 95% CI= 0.95 to 2.07). There was little evidence that this effect was greater for more advanced stage/ grade cancers (ORAA V GG= 1.78, 95% CI= 0.99 to 3.21) versus less advanced cancers (ORAA V GG= 1.23, 95% CI= 0.77 to 1.94) (p for interaction = 0.33). The rs1799884 genotype was not associated with PSA concentration, suggesting that any effect on prostate cancer risk is not attributable to PSA detection bias. Our results provide suggestive evidence for a link between a genotype associated with type 2 diabetes mellitus and PSA-detected prostate cancer. We hypothesize that hyperglycaemia may be important in mediating this relationship. PMID:21537389

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

PubMed

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic differences exist between these two tumors that may be important for future therapeutic strategies.

How allele frequency and study design affect association test statistics with misrepresentation errors.

PubMed

Escott-Price, Valentina; Ghodsi, Mansoureh; Schmidt, Karl Michael

2014-04-01

We evaluate the effect of genotyping errors on the type-I error of a general association test based on genotypes, showing that, in the presence of errors in the case and control samples, the test statistic asymptotically follows a scaled non-central $\\chi ^2$ distribution. We give explicit formulae for the scaling factor and non-centrality parameter for the symmetric allele-based genotyping error model and for additive and recessive disease models. They show how genotyping errors can lead to a significantly higher false-positive rate, growing with sample size, compared with the nominal significance levels. The strength of this effect depends very strongly on the population distribution of the genotype, with a pronounced effect in the case of rare alleles, and a great robustness against error in the case of large minor allele frequency. We also show how these results can be used to correct $p$-values.

Mycoplasma and ureaplasma infection and male infertility: a systematic review and meta-analysis.

PubMed

Huang, C; Zhu, H L; Xu, K R; Wang, S Y; Fan, L Q; Zhu, W B

2015-09-01

The relationship between mycoplasma and ureaplasma infection and male infertility has been studied widely; however, results remain controversial. This meta-analysis investigated the association between genital ureaplasmas (Ureaplasma urealyticum, Ureaplasma parvum) and mycoplasmas (Mycoplasma hominis, Mycoplasma genitalium), and risk of male infertility. Differences in prevalence of ureaplasma and mycoplasma infection between China and the rest of the world were also compared. Study data were collected from PubMed, Embase and the China National Knowledge Infrastructure. Summary odds ratio (OR) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing and publication bias testing were also performed. A total of 14 studies were used: five case-control studies with 611 infertile cases and 506 controls featuring U. urealyticum infection, and nine case-control studies with 2410 cases and 1223 controls concerning M. hominis infection. Two other infection (U. parvum and M. genitalium) were featured in five and three studies, respectively. The meta-analysis results indicated that U. parvum and M. genitalium are not associated with male infertility. However, a significant relationship existed between U. urealyticum and M. hominis and male infertility. Comparing the global average with China, a significantly higher positive rate of U. urealyticum, but a significantly lower positive rate of M. hominis, was observed in both the infertile and control groups in China. © 2015 American Society of Andrology and European Academy of Andrology.

Whole genome sequencing reveals an outbreak of Salmonella Enteritidis associated with reptile feeder mice in the United Kingdom, 2012-2015.

PubMed

Kanagarajah, Sanch; Waldram, Alison; Dolan, Gayle; Jenkins, Claire; Ashton, Philip M; Carrion Martin, Antonio Isidro; Davies, Robert; Frost, Andrew; Dallman, Timothy J; De Pinna, Elizabeth M; Hawker, Jeremy I; Grant, Kathie A; Elson, Richard

2018-05-01

Analysis of whole genome sequencing data uncovered a previously undetected outbreak of Salmonella Enteritidis that had been on-going for four years. Cases were resident in all countries of the United Kingdom and 40% of the cases were aged less than 11 years old. Initial investigations revealed that 30% of cases reported exposure to pet snakes. A case-control study was designed to test the hypothesis that exposure to reptiles or their feed were risk factors. A robust case-definition, based on the single nucleotide polymorphism (SNP) profile, increased the power of the analytical study. Following univariable and multivariable analysis, exposure to snakes was the only variable independently associated with infection (Odds ratio 810 95% CI (85-7715) p < 0.001). Isolates of S. Enteritidis belonging to the outbreak profile were recovered from reptile feeder mice sampled at the retail and wholesale level. Control measures included improved public health messaging at point of sale, press releases and engagement with public health and veterinary counterparts across Europe. Mice destined to be fed to reptiles are not regarded as pet food and are not routinely tested for pathogenic bacteria. Routine microbiological testing to ensure feeder mice are free from Salmonella is recommended. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Transcranial Doppler-based assessment of cerebral autoregulation in critically ill children during diabetic ketoacidosis treatment.

PubMed

Ma, Li; Roberts, Joan S; Pihoker, Catherine; Richards, Todd L; Shaw, Dennis W W; Marro, Ken I; Vavilala, Monica S

2014-10-01

Impaired cerebral autoregulation may be associated with poor outcome in diabetic ketoacidosis. We examined change in cerebral autoregulation during diabetic ketoacidosis treatment. Prospective observational cohort study. Tertiary care children's hospital. Children admitted to the ICU with diabetic ketoacidosis (venous pH < 7.3, glucose > 300 mg/dL, HCO3 < 15 mEq/L, and ketonuria) constituted cases, and children with type I diabetes without diabetic ketoacidosis constituted controls. None. Between 2005 and 2009, 32 cases and 50 controls were enrolled. Transcranial Doppler ultrasonography was used to measure middle cerebral artery flow velocities, and cerebral autoregulation testing was achieved via tilt-table testing. Cases underwent two and controls underwent one cerebral autoregulation test. Cerebral autoregulation was quantified by the autoregulatory index (autoregulatory index < 0.4 = impaired and autoregulatory index 0.4-1.0 = intact autoregulation). The first autoregulation test was obtained early (time 1, 12-24 hr; median [interquartile range], 8 hr [5-18 hr]) during diabetic ketoacidosis treatment, and a second autoregulation test was obtained during recovery (time 2, 36-72 hr; median [ interquartile range], 46 hr [40-59 hr]) from time 0 (defined as time of insulin start). Cases had lower autoregulatory index at time 1 than time 2 (p < 0.001) as well lower autoregulatory index than control subjects (p < 0.001). Cerebral autoregulation was impaired in 40% (n = 13) of cases at time 1 and in 6% (n = 2) of cases at time 2. Five cases (17%) showed persistent impairment of cerebral autoregulation between times 1 and 2 of treatment. All control subjects had intact cerebral autoregulation. Impaired cerebral autoregulation was common early during diabetic ketoacidosis treatment. Although the majority improved during diabetic ketoacidosis treatment, 17% of subjects had impairment between 36 and 72 hours after start of insulin therapy. The observed impaired cerebral autoregulation appears specific to the diabetic ketoacidosis process in patients with type I diabetes.

High Seroprevalence of Toxoplasma Gondii Infection in Female Sex Workers: A Case-Control Study

PubMed Central

Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Arreola-Cháidez, Emilio; López, Juan; Salcido-Meraz, Karla Itzel; Estrada-Martínez, Sergio; Navarrete-Flores, José Antonio; Pérez-Álamos, Alma Rosa; Hernández-Ochoa, Marcia; Rábago-Sánchez, Elizabeth; Liesenfeld, Oliver

2015-01-01

Through an age- and sex-matched case-control study, we sought to determine whether female sex workers have an increased risk of Toxoplasma gondii exposure and to determine the sociodemographic, work, clinical, and behavioral characteristics of these workers associated with T. gondii exposure. Female workers (n = 136) and controls (n = 272) were examined with enzyme-linked immunoassays (EIA) for the presence of anti-Toxoplasma IgG and IgM antibodies. IgM positive sera were additionally tested with enzyme linked-fluorescence immunoassay (ELFA). Anti-T. gondii IgG antibodies were found in 21 (15.44%) of 136 cases and in 10 (3.67%) of 272 controls (OR = 4.05; 95% CI: 1.84–8.89; P = 0.0001). Anti-T. gondii IgG levels higher than 150 IU/ml were found in 13 (9.6%) of 136 cases and in 8 (2.9%) of 272 controls (P = 0.007). Anti-T. gondii IgM antibodies were found in two cases and in six controls by EIA, but all were negative by ELFA. T. gondii seropositivity was associated with being born out of Durango State (OR = 10.47; 95% CI: 2.9–36.8; P < 0.01), injuries during sex work (OR = 6.30; 95% CI: 1.1–33.7; P = 0.03), and soil contact (OR = 4.11; 95% CI: 1.2–14.0; P = 0.02). This is the first report of an association of T. gondii infection and female sex workers. PMID:26716017

Hospital admissions for ischemic stroke: does long-term exposure to air pollution interact with major risk factors?

PubMed

Oudin, Anna; Strömberg, Ulf; Jakobsson, Kristina; Stroh, Emilie; Lindgren, Arne G; Norrving, Bo; Pessah-Rasmussen, Hélène; Engström, Gunnar; Björk, Jonas

2011-01-01

The aim was to investigate whether the effects of major risk factors for ischemic stroke were modified by long-term exposure to air pollution in Scania, southern Sweden. Cases were defined as first-ever ischemic strokes in patients born between 1923 and 1965 during 2001-2006 (n = 7,244). Data were collected from The Swedish National Stroke Register (Riks-stroke) and the Malmö and Lund Stroke Registers. Population controls were matched on age and sex. Modeled outdoor annual mean NO(x) concentrations were used as proxy for long-term exposure to air pollution. Heterogeneity across NO(x) categories was tested for smoking, hypertension, diabetes mellitus, atrial fibrillation and physical inactivity. Data were analyzed as case-control data and to some extent as case-only data, with logistic regression analysis. The case-control odds ratios for ischemic stroke in association with diabetes were 1.3 [95% confidence interval (CI): 1.1-1.6] and 2.0 (95% CI: 1.2-3.4) in the lowest and highest NO(x) category, respectively (p value for testing heterogeneity across the categories = 0.056). The case-only approach gave further support for the risk associated with diabetes to increase with NO(x) (p for trend = 0.033). We observed no main effect of mean NO(x) or any conclusive effect modifications between NO(x) and smoking, hypertension, atrial fibrillation or physical inactivity. In a low-level air pollution area, the risk for ischemic stroke associated with diabetes seemed to increase with long-term exposure to air pollution. Copyright © 2010 S. Karger AG, Basel.

Investigation of a Guillain-Barré syndrome cluster in the Republic of Fiji.

PubMed

Pastula, Daniel M; Khan, Aalisha Sahu; Sharp, Tyler M; Biaukula, Viema L; Naivalu, Taina K; Rafai, Eric; Ermias Belay; Staples, J Erin; Fischer, Marc; Kosoy, Olga I; Laven, Janeen J; Bennett, Elizabeth J; Jenney, Adam W J; Naidu, Ravi Narayan; Lanciotti, Robert S; Galloway, Renee L; Nilles, Eric J; Sejvar, James J; Kama, Mike

2017-01-15

In 2014, we investigated a cluster of Guillain-Barre syndrome (GBS) in Fiji that occurred during a dengue epidemic. We designed a case-control study to determine the etiology. Cases were patients meeting Brighton Collaboration criteria for GBS with onset from February 2014 to May 2014. Controls were persons without symptoms of GBS who were matched by age group and location. We collected information on demographics and potential exposures. Serum samples were tested for evidence of recent arboviral or Leptospira spp. infections. Nine cases of GBS were identified for an incidence of five cases per 100,000 population/year. Median age of cases was 27years (range: 0.8-52); five (56%) were male. Six (67%) reported an acute illness prior to GBS onset. Among the 9 cases and 28 controls enrolled, odds ratios for reported exposures or antibodies against various arboviruses or Leptospira spp. were not statistically significant. No clear etiologies were identified for this unusual GBS cluster. There was a temporal association between the GBS cluster and a dengue epidemic, but we were unable to substantiate an epidemiologic or laboratory association. Further study is needed to explore potential associations between arboviral infections and GBS. Copyright © 2016. Published by Elsevier B.V.

HIV infection among U.S. Army and Air Force military personnel: sociodemographic and genotyping analysis.

PubMed

Singer, Darrell E; Bautista, Christian T; O'Connell, Robert J; Sanders-Buell, Eric; Agan, Brian K; Kijak, Gustavo H; Hakre, Shilpa; Sanchez, Jose L; Sateren, Warren B; McCutchan, Francine E; Michael, Nelson L; Scott, Paul T

2010-08-01

Since 1985, the U.S. Department of Defense has periodically screened all military personnel for HIV allowing for the monitoring of the infection in this dynamic cohort population. A nested case-control study was performed to study sociodemographics, overseas assignment, and molecular analysis of HIV. Cases were newly identified HIV infections among U.S. Army and Air Force military personnel from 2000 to 2004. Controls were frequency matched to cases by gender and date of case first positive HIV screening test. Genotyping analysis was performed using high-throughput screening assays and partial genome sequencing. HIV was significantly associated with black race [odds ratio (OR) = 6.65], single marital status (OR = 4.45), and age (OR per year = 1.07). Ninety-seven percent were subtype B and 3% were non-B subtypes (A3, CRF01_AE, A/C recombinant, G, CRF02_AG). Among cases, overseas assignment in the period at risk prior to their first HIV-positive test was associated with non-B HIV subtype infection (OR = 8.44). Black and single military personnel remain disproportionately affected by HIV infection. Most non-B HIV subtypes were associated with overseas assignment. Given the increased frequency and length of assignments, and the expanding HIV genetic diversity observed in this population, there is a need for active HIV genotyping surveillance and a need to reinforce primary HIV prevention efforts.

Antilock brakes and the risk of driver injury in a crash: a case-control study.

PubMed

Cummings, Peter; Grossman, David C

2007-09-01

While antilock brakes can improve steering and reduce stopping distance in some test situations, there is little evidence that they reduce the risk of crash-related injury. We sought to estimate the association between presence of antilock brakes and the risk of driver injury. We conducted a case-control study using claims data from the Insurance Corporation of British Columbia, Canada, for passenger vehicles insured during July 1, 2003, to June 30, 2004. Cases were 5000 vehicles with a driver crash injury during the study period. Controls were 49,994 vehicles insured at the mid-point of the study interval. The adjusted risk ratio for a crash with driver injury in a vehicle with antilock brakes was 1.06 (95% confidence interval, 0.95-1.17), compared with a vehicle without antilock brakes. If this estimated association is causal, antilock brakes do not prevent crash-related driver injuries.

A simple test of association for contingency tables with multiple column responses.

PubMed

Decady, Y J; Thomas, D R

2000-09-01

Loughin and Scherer (1998, Biometrics 54, 630-637) investigated tests of association in two-way tables when one of the categorical variables allows for multiple-category responses from individual respondents. Standard chi-squared tests are invalid in this case, and they developed a bootstrap test procedure that provides good control of test levels under the null hypothesis. This procedure and some others that have been proposed are computationally involved and are based on techniques that are relatively unfamiliar to many practitioners. In this paper, the methods introduced by Rao and Scott (1981, Journal of the American Statistical Association 76, 221-230) for analyzing complex survey data are used to develop a simple test based on a corrected chi-squared statistic.

Visits on 'lamb-viewing days' at a sheep farm open to the public was a risk factor for Q fever in 2009.

PubMed

Whelan, J; Schimmer, B; de Bruin, A; van Beest Holle, M Robert-du Ry; van der Hoek, W; ter Schegget, R

2012-05-01

Between February and May 2009, 347 laboratory-confirmed cases of acute Q fever were reported in a southern municipal health service region in The Netherlands. Commercial dairy-goat farms were implicated and control measures were initially targeted there. A preliminary investigation also implicated a non-dairy sheep farm, open to the public on 'lamb-viewing days'. This study tested the association between visiting the non-dairy sheep farm and developing Q fever in residents of the region between February and May 2009. A case-control study of 146 cases and 431 address-matched controls was conducted. Multivariable logistic regression analysis confirmed the association between visiting to the sheep farm and Q fever disease (matched odds ratio 43, 95% confidence interval 9-200). Other risk factors were being a smoker, having a past medical history and being aged >40 years. Vaccination of sheep and goats on farms open to the public should help to reduce the number of future human cases.

Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study.

PubMed

Jyonouchi, Harumi; Geng, Lee; Cushing-Ruby, Agnes; Quraishi, Huma

2008-11-21

Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. This study assessed whether these clinical features of this ASD subset are associated with atopy, asthma, food allergy (FA), primary immunodeficiency (PID), or innate immune responses important in viral infections. This study included the ASD children described above (ASD test, N = 26) and the following controls: ASD controls (N = 107), non-ASD controls with FA (N = 24), non-ASD controls with chronic rhinosinusitis/recurrent otitis media (CRS/ROM; N = 38), and normal controls (N = 43). We assessed prevalence of atopy, asthma, FA, CRS/ROM, and PID. Innate immune responses were assessed by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of Toll-like receptors (TLRs), with or without pre-treatment of lipopolysaccharide (LPS), a TLR4 agonist. Non-IgE mediated FA was equally prevalent in both ASD test and ASD control groups, occurring at higher frequency than in the non-ASD controls. Allergic rhinitis, atopic/non-atopic asthma, and atopic dermatitis were equally prevalent among the study groups except for the CRS/ROM group in which non-atopic asthma was more prevalent (52.6%). CRS/ROM and specific polysaccharide antibody deficiency (SPAD) were more prevalent in the ASD test group than in the ASD control, FA, and normal control groups: 23.1% vs. < 5% for CRS/ROS and 19.2% vs. < 1% for SPAD. However, CRS/ROM patients had the highest prevalence of SPAD (34.2%). When compared to ASD and normal case controls, PBMCs from 19 non-SPAD, ASD test group children produced: 1) less IL-1beta with a TLR7/8 agonist, less IL-10 with a TLR2/6 agonist, and more IL-23 with a TLR4 agonist without LPS pre-treatment, and 2) less IL-1beta with TLR4/7/8 agonists with LPS pre-treatment. These are cytokines associated with the neuro-immune network. Clinical features of the ASD test group were not associated with atopy, asthma, FA, or PID in our study but may be associated with altered TLR responses mediating neuro-immune interactions.

Bayes Factor based on the Trend Test Incorporating Hardy-Weinberg Disequilibrium: More Powerful to Detect Genetic Association

PubMed Central

Xu, Jinfeng; Yuan, Ao; Zheng, Gang

2012-01-01

Summary In the analysis of case-control genetic association, the trend test and Pearson’s test are the two most commonly used tests. In genome-wide association studies (GWAS), Bayes factor is a useful tool to support significant p-values, and a better measure than p-value when results are compared across studies with different sample sizes. When reporting the p-value of the trend test, we propose a Bayes factor directly based on the trend test. To improve the power to detect association under recessive or dominant genetic models, we propose a Bayes factor based on the trend test and incorporating Hardy-Weinberg disequilibrium in cases. When the true model is unknown, or both the trend test and Pearson’s test or other robust tests are applied in genome-wide scans, we propose a joint Bayes factor, combining the previous two Bayes factors. All three Bayes factors studied in this paper have closed forms and are easy to compute without integrations, so they can be reported along with p-values, especially in GWAS. We discuss how to use each of them and how to specify priors. Simulation studies and applications to three GWAS are provided to illustrate their usefulness to detect non-additive gene susceptibility in practice. PMID:22607017

Dyslexia and Dyscalculia: Two Learning Disorders with Different Cognitive Profiles

ERIC Educational Resources Information Center

Landerl, Karin; Fussenegger, Barbara; Moll, Kristina; Willburger, Edith

2009-01-01

This study tests the hypothesis that dyslexia and dyscalculia are associated with two largely independent cognitive deficits, namely a phonological deficit in the case of dyslexia and a deficit in the number module in the case of dyscalculia. In four groups of 8- to 10-year-olds (42 control, 21 dyslexic, 20 dyscalculic, and 26…

Association of the homeobox transcription factor gene ENGRAILED 2 with autistic disorder in Chinese children.

PubMed

Yang, Pinchen; Lung, For-Wey; Jong, Yuh-Jyh; Hsieh, Hsin-Yi; Liang, Chung-Ling; Juo, Suh-Hang Hank

2008-01-01

Autism is a neurodevelopmental disorder with a strong genetic component. Previous studies have mapped the disease to chromosome 7q, where the homeobox transcription factor ENGRAILED 2 (EN2) gene is located. EN2 is specifically involved in patterning the region that gives rise to the cerebellum. In the present work, we carried out a case-control study to determine whether 2 intronic single-nucleotide polymorphisms (SNPs) of EN2 are a susceptibility to autism in a Han Chinese population. We enrolled 184 cases of DSM-IV-TR diagnosed autistic disorder, 225 controls of unrelated healthy volunteers and 409 randomly selected controls from the community who lives in the adjacent geographical regions for this study. Two SNPs (rs1861972, rs1861973) at the EN2 gene that have been reported to be associated with autism underwent analysis among our studied cohorts. Both the UNPHASE and PHASE statistical programs were utilized for evaluating the association of EN2 SNPs with autism based on allelic and genotypic frequencies and haplotype compositions accompanied with the goodness-of-fit method of the chi(2) test. The gender difference was also investigated by using 2-side Fisher's exact test treated as a covariate in logistic regression analysis. Both the allelic and genotypic distributions of the 2 polymorphisms were concordant with Hardy-Weinberg equilibrium. Significant differences were found for cases versus community and overall controls. By using the UNPHASE and PHASE programs, the 2-marker haplotype A-C of EN2 was identified to have a protective effect for autism, indicating that the ethnic difference might confound the EN2 association with autism. Therefore, more EN2 gene association studies of Han Chinese populations are warranted to confirm this finding. 2008 S. Karger AG, Basel.

Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study.

PubMed

Stark, Klaus; Reinhard, Wibke; Neureuther, Katharina; Wiedmann, Silke; Sedlacek, Kamil; Baessler, Andrea; Fischer, Marcus; Weber, Stefan; Kaess, Bernhard; Erdmann, Jeanette; Schunkert, Heribert; Hengstenberg, Christian

2008-04-09

Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population.

Early life predictors of preschool overweight and obesity: a case-control study in Sri Lanka.

PubMed

Rathnayake, Kumari M; Satchithananthan, Aberna; Mahamithawa, Senarath; Jayawardena, Ranil

2013-10-22

Childhood obesity increases the risk of obesity in adulthood and is associated with cardiovascular disease risk factors. Our aim was to assess the early life risk factors associated with overweight and obesity among preschool children. In this case-control study, from the 1087 preschool children measured, age, sex and ethnicity matched 71 cases and 71 controls were recruited. Cases and controls were defined according to the WHO 2006 growth standards. The birth and growth characteristics were extracted from the child health development records. Infant feeding practices and maternal factors were obtained from the mother. Rapid weight gain was defined as an increase in weight-for-age Z score (WHO standards) above 0.67 SD from birth to 2 years. The magnitude and significant difference in mean values of the variables associated with overweight and obesity were evaluated using logistic regressions and paired t-test, respectively. Cases had significantly shorter duration (months) of breastfeeding (19.4, 24.6, p = 0.003), and smaller duration (months) of exclusive breastfeeding (3.7, 5.1, p = 0.001) compared to controls. Rapid weight gain (OR = 6.3, 95% CI = 2.04-19.49), first born status (OR = 3.6, 95% CI = 1.17-10.91) and pre-pregnancy obesity (OR = 4.0, 95% CI = 1.46-10.76) were positively associated with overweight and obesity. Breastfeeding more than 2 years (OR = 0.2, 95% CI = 0.06-0.57) was negatively associated with overweight and obesity. Rapid weight gain within first two years, first-born status and pre-pregnancy obesity of the mother contributed for preschool obesity. Our results suggest that intervention may be indicated earlier in infancy and during the toddler and preschool years to tackle the increasing prevalence of obesity.

Comprehensive evaluation of the Estrogen Receptor Alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population

PubMed Central

Keene, Keith L.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Leak, Tennille S.; Perlegas, Peter S.; Langefeld, Carl D.; Herrington, David M.; Freedman, Barry I.; Rich, Stephen S.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

We previously investigated the estrogen receptor α gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and type 2 diabetes and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and End Stage Renal Disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a χ2 statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P< 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P=0.000291, adjusted P=0.0289), and intron 4 SNPs rs1569788 (nominal P=0.000754, adjusted P=0.0278) and rs9340969 (nominal P=0.00109, adjusted P=0.0467) remained significant at experimentwise error rate (EER) P<0.05 for the dominant class of tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4-intron 6 region. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls) and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy. PMID:18305958

Comprehensive evaluation of the estrogen receptor alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population.

PubMed

Keene, Keith L; Mychaleckyj, Josyf C; Smith, Shelly G; Leak, Tennille S; Perlegas, Peter S; Langefeld, Carl D; Herrington, David M; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

2008-05-01

We previously investigated the estrogen receptor alpha gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found evidence for association between the intron 1-intron 2 region of this gene and T2DM and/or nephropathy in an African American (AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA with T2DM and end stage renal disease (T2DM-ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577 AA individuals with T2DM-ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models, and haplotypic association, were calculated using a chi(2) statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P < 0.05) with T2DM-ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal P = 0.000291, adjusted P = 0.0289), and intron 4 SNPs rs1569788 (nominal P = 0.000754, adjusted P = 0.0278) and rs9340969 (nominal P = 0.00109, adjusted P = 0.0467) remained significant at experimentwise error rate (EER) P

Lack of association of the serotonin transporter polymorphism with the sudden infant death syndrome in the San Diego Dataset.

PubMed

Paterson, David S; Rivera, Keith D; Broadbelt, Kevin G; Trachtenberg, Felicia L; Belliveau, Richard A; Holm, Ingrid A; Haas, Elisabeth A; Stanley, Christina; Krous, Henry F; Kinney, Hannah C; Markianos, Kyriacos

2010-11-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS.

Lack of Association of the Serotonin Transporter Polymorphism With the Sudden Infant Death Syndrome in the San Diego Dataset

PubMed Central

Paterson, David S.; Rivera, Keith D.; Broadbelt, Kevin G.; Trachtenberg, Felicia L.; Belliveau, Richard A.; Holm, Ingrid A.; Haas, Elisabeth A.; Stanley, Christina; Krous, Henry F.; Kinney, Hannah C.; Markianos, Kyriacos

2011-01-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS. PMID:20661167

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

PubMed Central

van Manen, Daniëlle; Bunnik, Evelien M.; van Sighem, Ard I.; Sieberer, Margit; Boeser-Nunnink, Brigitte; de Wolf, Frank; Schuitemaker, Hanneke; Portegies, Peter; Kootstra, Neeltje A.; van 't Wout, Angélique B.

2012-01-01

Background Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. Methods We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. Results The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2×10−5). Prep1 has recently been identified as a transcription factor preferentially binding the −2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. Conclusion These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders. PMID:22347417

A 2cM genome-wide scan of European Holstein cattle affected by classical BSE

PubMed Central

2010-01-01

Background Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with variations in transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism (SNP) markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic. Results Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set of paired cases with controls. The family set comprises half-sibling progeny from six sires. The progeny from four of these sires had previously been scanned with microsatellite markers. The results obtained from the current analysis of the family set yielded both some supporting and new results compared with those obtained in the earlier study. The results revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease. These results confirm a region previously reported on chromosome 20, and identify additional regions on chromosomes 2, 14, 16, 21 and 28. This study did not identify a significant association near the PRNP in the family sample set. The only association found in the PRNP region was in the case-control sample set and this was not significant after multiple test correction. The genome scan of the case-control animals did not identify any associations that passed a stringent genome-wide significance threshold. Conclusions Several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. Further investigation of loci on chromosomes 2, 14, 16, 20, 21 and 28 will be required to uncover any biological significance underlying these marker associations. PMID:20350325

Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning.

PubMed

Schier, J G; Hunt, D R; Perala, A; McMartin, K E; Bartels, M J; Lewis, L S; McGeehin, M A; Flanders, W D

2013-12-01

Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6-75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14-118.4) and only five (23%) controls (median, < Lower Limit of Quantitation (LLQ); range, < LLQ-43.3 mcg/mL). Significant differences and associations were identified between case status and the following: 1) serum oxalic acid and serum HEAA (both OR = 14.6; 95% C I = 2.8-100.9); 2) serum diglycolic acid and urine diglycolic acid (both OR > 999; exact p < 0.0001); and 3) urinary glycolic acid (OR = 0.057; 95% C I = 0.001-0.55). Two CSF sample results were excluded and two from the same case were averaged, yielding eight samples from eight cases. Diglycolic acid was detected in seven (88%) of case CSF samples (median, 2.03 mcg/mL; range, < LLQ, 7.47). Significantly elevated HEAA (serum) and diglycolic acid (serum and urine) concentrations were identified among cases, which is consistent with animal data. Low urinary glycolic acid concentrations in cases may have been due to concurrent AKI. Although serum glycolic concentrations among cases may have initially increased, further metabolism to oxalic acid may have occurred thereby explaining the similar glycolic acid concentrations in cases and controls. The increased serum oxalic acid concentration results in cases versus controls are consistent with this hypothesis. Diglycolic acid is associated with human DEG poisoning and may be a biomarker for poisoning. These findings add to animal data suggesting a possible role for traditional antidotal therapies. The detection of HEAA and diglycolic acid in the CSF of cases suggests a possible association with signs and symptoms of DEG-associated neurotoxicity. Further work characterizing the pathophysiology of DEG-associated neurotoxicity and the role of traditional toxic alcohol therapies such as fomepizole and hemodialysis is needed.

A Two-Phase Case-Control Study of Autism Risk Among Children Born From the Late 1990s Through the Early 2000s in the United States.

PubMed

Geier, David A; Kern, Janet K; Geier, Mark R

2016-12-29

BACKGROUND This study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism. MATERIAL AND METHODS A two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken. RESULTS Analysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998-2003. CONCLUSIONS This study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

Patterns and determinants of malaria risk in urban and peri-urban areas of Blantyre, Malawi.

PubMed

Mathanga, Don P; Tembo, Atupele Kapito; Mzilahowa, Themba; Bauleni, Andy; Mtimaukenena, Kondwani; Taylor, Terrie E; Valim, Clarissa; Walker, Edward D; Wilson, Mark L

2016-12-08

Although malaria disease in urban and peri-urban areas of sub-Saharan Africa is a growing concern, the epidemiologic patterns and drivers of transmission in these settings remain poorly understood. Factors associated with variation in malaria risk in urban and peri-urban areas were evaluated in this study. A health facility-based, age and location-matched, case-control study of children 6-59 months of age was conducted in four urban and two peri-urban health facilities (HF) of Blantyre city, Malawi. Children with fever who sought care from the same HF were tested for malaria parasites by microscopy and PCR. Those testing positive or negative on both were defined as malaria cases or controls, respectively. A total of 187 cases and 286 controls were studied. In univariate analyses, higher level of education, possession of TV, and electricity in the house were negatively associated with malaria illness; these associations were similar in urban and peri-urban zones. Having travelled in the month before testing was strongly associated with clinical malaria, but only for participants living in the urban zones (OR = 5.1; 95% CI = 1.62, 15.8). Use of long-lasting insecticide nets (LLINs) the previous night was not associated with protection from malaria disease in any setting. In multivariate analyses, electricity in the house, travel within the previous month, and a higher level of education were all associated with decreased odds of malaria disease. Only a limited number of Anopheles mosquitoes were found by aspiration inside the households in the peri-urban areas, and none was collected from the urban households. Travel was the main factor influencing the incidence of malaria illness among residents of urban Blantyre compared with peri-urban areas. Identification and understanding of key mobile demographic groups, their behaviours, and the pattern of parasite dispersal is critical to the design of more targeted interventions for the urban setting.

Sperm count and motility are quantitatively affected by functional polymorphisms of HTR2A, MAOA and SLC18A.

PubMed

Cortés-Rodriguez, Miriam; Royo, Jose-Luis; Reyes-Palomares, Arturo; Lendínez, Ana M; Ruiz-Galdón, Maximiliano; Reyes-Engel, Armando

2018-05-01

Spermatozoa and neurones share similar membrane characteristics and features. Associations of multiple polymorphisms traditionally related to neurotransmission were investigated. Infertile men were grouped into controls with normospermia (n = 182) and idiopathic infertile men with asthenozoospermia (n = 103), and analysed as a case-control study and as a quantitative association of each genotype. Ten neurotransmission-associated genetic variants were mapped by SNP analysis using quantitative polymerase chain reaction with TaqMan probes. Men with HTR2A rs6313 had a higher risk of asthenozoospermia (OR = 2.14; P = 0.04). MAOA rs3788862 G carriers displayed an increased risk of asthenozoospermia (OR = 2.29; P = 0.02). The SLC18A1 rs1390938 G allele was more frequent among such cases (0.75 versus 0.87; P < 0.01 and P < 0.01 for Armitage trend test); for SLC18A1 rs2270641 P = 0.02 (case-control frequency) and P = 0.01 (Armitage trend test). MAOA rs3788862 was correlated with sperm motility (Spearman ρ = 0.14; P = 0.02); SLC18A1 rs1390938 was correlated with sperm count and motility (Spearman ρ = 0.20; P < 0.01). Gene polymorphisms of HTR2A, MAOA and SLC18A1, related to neurotransmission, are individually associated with asthenozoospermia through variation in sperm count and motility, without detectable allelic or genotype interaction. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The Association Between Mild Intraoperative Hypotension and Stroke in General Surgery Patients.

PubMed

Hsieh, Jason K; Dalton, Jarrod E; Yang, Dongsheng; Farag, Ehab S; Sessler, Daniel I; Kurz, Andrea M

2016-10-01

Intraoperative hypotension may contribute to perioperative strokes. We therefore tested the hypothesis that intraoperative hypotension is associated with perioperative stroke. After institutional review board approval for this case-control study, we identified patients who had nonneurological, noncardiac, and noncarotid surgery under general anesthesia at the Cleveland Clinic between 2005 and 2011 and experienced a postoperative stroke. Control patients not experiencing postoperative stroke were matched in a 4-to-1 ratio using propensity scores and restriction to the same procedure type as stroke patients. The association between intraoperative hypotension, measured as time-integrated area under a mean arterial pressure (MAP) of 70 mm Hg, and postoperative stroke was assessed using zero-inflated negative binomial regression. Among 106 337 patients meeting inclusion criteria, we identified 120 who had confirmed postoperative stroke events based on manual chart review. Four-to-one propensity matching yielded a final matched sample of 104 stroke cases and 398 controls. There was no association between stroke and intraoperative hypotension. Stroke patients were not more likely than controls to have been hypotensive (odds ratio, 0.49 [0.18-1.38]), and among patients with intraoperative hypotension, stroke patients did not experience a greater degree of hypotension than controls (ratio of geometric means, 1.07 [0.76-1.53]). In our propensity score-matched case-control study, we did not find an association between intraoperative hypotension, defined as MAP < 70 mm Hg, and postoperative stroke.

The Association Between the Genetic Variants of the NOTCH3 Gene and Ischemic Stroke Risk.

PubMed

Yuan, Xiaoling; Dong, Zifeng

2016-10-22

BACKGROUND Ischemic stroke (IS) is a leading cause of disability and death and NOTCH3 as a gene related with cardiac-cerebral vascular disease plays a vital role in IS development. However, the reports about the effect of genetic variants in NOTCH3 gene on IS are still few. MATERIAL AND METHODS In order to explore the association between NOTCH3 polymorphisms and IS, 134 patients with IS and 115 controls were enrolled in this case-control study. Polymerase chain reaction was used to do the genotyping of polymorphisms. The χ² test was performed to evaluate Hardy-Weinberg equilibrium (HWE) in the control group and calculate odds ratio (OR) with corresponding 95% confidence interval (CI) which represented the association intensity of NOTCH3 gene polymorphisms and IS risk. RESULTS The genotype frequencies in the control group all confirmed to HWE. TT genotype of 381C>T was associated significantly with IS risk (OR=2.441, 95%CI=1.021-5.837). TC, CC mutant genotypes of 1735T>C had higher frequencies in cases than controls and the difference was significant (P=0.013, 0.041); further, its C allele also increased 0.722 times risk in the case group than controls (OR=1.722, 95%CI=1.166-2.541). CONCLUSIONS NOTCH3 381C>T and 1735T>C polymorphisms were associated with IS and might be the risk factors for IS development, but not NOTCH3 605C>T polymorphism.

Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study.

PubMed

Woo, Daniel; Kaushal, Ritesh; Kissela, Brett; Sekar, Padmini; Wolujewicz, Michael; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Ewing, Irene; Miller, Rosie; Kleindorfer, Dawn; Flaherty, Matthew; Chakraborty, Ranajit; Deka, Ranjan; Broderick, Joseph

2006-02-01

The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.

The influence of participation in target-shooting sport for children with inattentive, hyperactive and impulsive symptoms - A controlled study of best practice.

PubMed

Månsson, Annegrete Gohr; Elmose, Mette; Dalsgaard, Søren; Roessler, Kirsten K

2017-03-28

Practising target-shooting sport requires focused attention and motoric steadiness. A previous non-controlled pilot study suggests that children with impairing symptoms of attention-deficit/hyperactivity disorder (ADHD) benefit from participating in target-shooting sport in local shooting associations, as rated by parents and teachers. This study aims at examining if, and to which extent, target-shooting sport reduces parent- and teacher-reported severity of inattentiveness, hyperactivity, and impulsivity in children with attention difficulties, and if, and to which extend, target-shooting sport improves the children's wellbeing and quality of life. A mixed method approach is applied. A non-blinded, waiting list controlled study is combined with a case study, consisting of interviews and observations. The intervention consists of children practising target-shooting sport, by attending a local shooting association, once a week for six months, during regular school hours. Data from questionnaires (ADHD-RS, SDQ, Kidscreen-27), as well as a computerized continued performance test (Qb test), measure the children's activity and attention. The study includes 50 children in an intervention group and 50 children in a waiting list control group. The Qb test collects data from at least 20 children from the intervention group and at least 20 children from the waiting list control group. Data from the questionnaires and Qb-test is collected at baseline, and six months post intervention. In addition, a case study is carried out, consisting of interviews of at least five children from the intervention group, their parents, teachers and shooting instructors. Observations are carried out, when children are in school and while they are attending the local shooting association. The case study adds to an in-depth understanding of children's participation in target-shooting sports. At present, little is known about the effects and influence of practising target-shooting sport for children experiencing difficulties with inattentiveness, hyperactivity and impulsivity. This study is expected to contribute to an understanding of the influence of participating in target-shooting sports on inattentive, hyperactive and impulsive symptoms, and the effects on the children's psychological wellbeing and quality of life. Current Controlled Trials NCT02898532 . Retrospectively registered 14 September 2016.

Testing for genetic association taking into account phenotypic information of relatives.

PubMed

Uh, Hae-Won; Wijk, Henk Jan van der; Houwing-Duistermaat, Jeanine J

2009-12-15

We investigated efficient case-control association analysis using family data. The outcome of interest was coronary heart disease. We employed existing and new methods that take into account the correlations among related individuals to obtain the proper type I error rates. The methods considered for autosomal single-nucleotide polymorphisms were: 1) generalized estimating equations-based methods, 2) variance-modified Cochran-Armitage (MCA) trend test incorporating kinship coefficients, and 3) genotypic modified quasi-likelihood score test. Additionally, for X-linked single-nucleotide polymorphisms we proposed a two-degrees-of-freedom test. Performance of these methods was tested using Framingham Heart Study 500 k array data.

Ultrasound analysis of mental artery flow in elderly patients: a case-control study.

PubMed

Baladi, Marina G; Tucunduva Neto, Raul R C M; Cortes, Arthur R G; Aoki, Eduardo M; Arita, Emiko S; Freitas, Claudio F

2015-01-01

Mental artery flow decreases with age and may have an aetiological role in alveolar ridge atrophy. The aim of this study was to identify factors associated with alterations of mental artery flow, assessed by ultrasonography. This case-control study was conducted on elderly patients (aged above 60 years) at the beginning of dental treatment. Intraoral B-mode Doppler ultrasonography was used to assess mental artery flow. The cases were defined as patients with a weak/absent ultrasound signal, whereas the controls presented a strong ultrasound signal. Demographics and radiographic findings (low bone mineral density on dual-energy X-ray absorptiometry and mandibular cortical index on panoramic radiographs) were analysed as risk factors for weak/absent ultrasound signal and were calculated as adjusted odds ratios (AORs) with 95% confidence intervals (CIs) using conditional logistic regression. In addition, the Student's t-test was used to compare the mean alveolar bone height of the analysed groups. A p-value <0.05 was considered statistically significant. A total of 30 ultrasound examinations (12 cases and 18 controls) were analysed. A weak/absent mental artery pulse strength was significantly associated with edentulism (AOR = 3.67; 95% CI = 0.86-15.63; p = 0.046). In addition, there was a significant difference in alveolar bone height between edentulous cases and controls (p = 0.036). Within the limitations of this study, the present results indicate that edentulism is associated with diminished mental artery flow, which, in turn, affects alveolar bone height.

Effect of Periodontal Disease on Preeclampsia

PubMed Central

Sayar, F; Hoseini, M Sadat; Abbaspour, S

2011-01-01

Background: A lot of studies have shown periodontal diseases as a risk factor for adverse pregnancy outcomes. The association between periodontitis and preeclampsia has been studied recently with controversy. Considering the importance of preventing preeclampsia as a dangerous and life-threatening disease in pregnant women, the present study was carried out. Methods: Two hundred and ten pregnant women participated in this case-control study (105 controls & 105 cases) during years 2007 and 2008. Preeclamptic cases were defined as blood pressure ≥140/90mmHg and proteinuria +1. Control group were pregnant women with normal blood pressure without proteinuria. Both groups were examined during 48 hours after child delivery. Plaque Index (PLI), Pocket Depth (PD), Clinical Attachment Level (CAL), Bleeding On Probing (BOP), Gingival Recession (GR) were measured on all teeth except for third molars and recorded as periodontal examination. Data was analyzed using t-test, chi-square, and Mann-Whitney U statistical tests. Results: There was no significant difference between the two study groups for PD. CAL, GR, BOP significantly increased in the case group (P< 0.02). This study showed that preeclamptic cases were more likely to develop periodontal disease (P< 0.0001). Eighty three percent of the control group and 95% of the case group had periodontal disease (P< 0.005) which had shown that preeclamptic cases were 4.1 times more likely to have periodontal disease (OR= 4.1). Conclusion: Preeclamptic cases significantly had higher attachment loss and gingival recession than the control group. PMID:23113094

Association of Interleukin-1 gene clusters polymorphisms with primary open-angle glaucoma: a meta-analysis.

PubMed

Li, Junhua; Feng, Yifan; Sung, Mi Sun; Lee, Tae Hee; Park, Sang Woo

2017-11-28

Previous studies have associated the Interleukin-1 (IL-1) gene clusters polymorphisms with the risk of primary open-angle glaucoma (POAG). However, the results were not consistent. Here, we performed a meta-analysis to evaluate the role of IL-1 gene clusters polymorphisms in POAG susceptibility. PubMed, EMBASE and Cochrane Library (up to July 15, 2017) were searched by two independent investigators. All case-control studies investigating the association between single-nucleotide polymorphisms (SNPs) of IL-1 gene clusters and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for quantifying the strength of association that has been involved in at least two studies. Five studies on IL-1β rs16944 (c. -511C > T) (1053 cases and 986 controls), 4 studies on IL-1α rs1800587 (c. -889C > T) (822 cases and 714 controls), and 4 studies on IL-1β rs1143634 (c. +3953C > T) (798 cases and 730 controls) were included. The results suggest that all three SNPs were not associated with POAG risk. Stratification analyses indicated that the rs1143634 has a suggestive associated with high tension glaucoma (HTG) under dominant (P = 0.03), heterozygote (P = 0.04) and allelic models (P = 0.02), however, the weak association was nullified after Bonferroni adjustments for multiple tests. Based on current meta-analysis, we indicated that there is lack of association between the three SNPs of IL-1 and POAG. However, this conclusion should be interpreted with caution and further well designed studies with large sample-size are required to validate the conclusion as low statistical powers.

Hyperthyroidism association with SLE, lessons from real-life data--A case-control study.

PubMed

Watad, Abdulla; Cohen, Arnon D; Comaneshter, Doron; Tekes-Manova, Dorit; Amital, Howard

2016-01-01

Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation. To investigate the association of comorbid SLE and hyperthyroidism. Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p < 0.001). In a multivariate analysis, SLE was associated with hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137). Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.

Association of Age Related Macular Degeneration and Age Related Hearing Impairment

PubMed Central

Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

2016-01-01

Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

Does iodine excess lead to hypothyroidism? Evidence from a case-control study in India.

PubMed

Kotwal, Atul; Kotwal, Jyoti; Prakash, Rajat; Kotwal, Narendra

2015-08-01

Iodine deficiency disorders have been known to mankind since antiquity and various researchers elucidated the role of iodine in its causation. However, recent evidence shows that the entire control program ignored multi-causality and association of increased iodine intake with hypothyroidism. This study was conducted to assess differences of iodine intake as measured by urinary iodine excretion (UIE) between cases of hypothyroidism and healthy controls. A case-control study was conducted with three groups (cases, hospital controls and community controls) in two cities of India. Patients with overt hypothyroidism were cases (n = 150) and were compared with age, sex and socioeconomic status-matched hospital (n = 154) and community (n = 488) controls. Thyroid function tests (T3, T4, TSH) were used as diagnostic and inclusion criteria. TPOAb and UIE estimation were carried out for all study participants. Mean values of TPOAb and UIE were higher in cases as compared to hospital controls as well as community controls (p <0.05). With a cut off of 34 IU/mL for TPOAb, more cases had an anti-TPO level >34 as compared to hospital controls (p <0.001) as well as community controls (p <0.001); OR, 0.06 (95% CI, 0.03, 0.12) and 0.08 (0.05, 0.12), respectively. For UIE cut-off of 300 μg/L, more cases than hospital controls (p = 0.090) and community controls (p = 0.001) had higher levels; OR, 0.671, (0.422, 1.066) and 0.509, (0.348, 0.744), respectively. The study has clearly shown that cases of hypothyroidism are associated with excess iodine intake. Cohort studies to generate further evidence and an eco-social epidemiological approach have been suggested as the way forward. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans

PubMed Central

Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Schellenberg, Gerard D.; Mayeux, Richard

2013-01-01

Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

PubMed

Deloria Knoll, Maria; Morpeth, Susan C; Scott, J Anthony G; Watson, Nora L; Park, Daniel E; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; O'Brien, Katherine L; Thea, Donald M; Ahmed, Dilruba; Antonio, Martin; Awori, Juliet O; Baillie, Vicky L; Chipeta, James; Deluca, Andrea N; Dione, Michel; Driscoll, Amanda J; Higdon, Melissa M; Jatapai, Anchalee; Karron, Ruth A; Mazumder, Razib; Moore, David P; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Seidenberg, Phil; Siludjai, Duangkamon; Sow, Samba O; Tamboura, Boubou; Zeger, Scott L; Murdoch, David R; Madhi, Shabir A

2017-06-15

Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Identifying disease polymorphisms from case-control genetic association data.

PubMed

Park, L

2010-12-01

In case-control association studies, it is typical to observe several associated polymorphisms in a gene region. Often the most significantly associated polymorphism is considered to be the disease polymorphism; however, it is not clear whether it is the disease polymorphism or there is more than one disease polymorphism in the gene region. Currently, there is no method that can handle these problems based on the linkage disequilibrium (LD) relationship between polymorphisms. To distinguish real disease polymorphisms from markers in LD, a method that can detect disease polymorphisms in a gene region has been developed. Relying on the LD between polymorphisms in controls, the proposed method utilizes model-based likelihood ratio tests to find disease polymorphisms. This method shows reliable Type I and Type II error rates when sample sizes are large enough, and works better with re-sequenced data. Applying this method to fine mapping using re-sequencing or dense genotyping data would provide important information regarding the genetic architecture of complex traits.

Elevated urinary leukotriene E4 levels are associated with hospitalization for pain in children with sickle cell disease.

PubMed

Jennings, Jeanine E; Ramkumar, Thiruvamoor; Mao, Jingnan; Boyd, Jessica; Castro, Mario; Field, Joshua J; Strunk, Robert C; DeBaun, Michael R

2008-08-01

Cysteinyl leukotrienes (CsyLTs) are inflammatory mediators produced by white blood cells. Leukotriene LTE(4) is the stable metabolite of CsyLTs, which can be measured in urine. We tested two hypotheses among children with sickle cell disease (SCD): (1) baseline urinary LTE(4) levels are elevated in children with SCD when compared with controls; and (2) baseline LTE(4) levels are associated with an increased incidence rate of hospitalization for SCD-related pain. Baseline LTE(4) levels were measured in children with SCD (cases) and children without SCD matched for age and ethnicity (controls). Medical records of cases were reviewed to assess the frequency of hospitalization for pain within 3 years of study entry. LTE(4) levels were obtained in 71 cases and 22 controls. LTE(4) levels were higher in cases compared with controls (median LTE(4): 100 vs. 57 pg/mg creatinine, P < 0.001). After adjustment for age and asthma diagnosis, a greater incidence rate of hospitalization for pain was observed among children with SCD in the highest LTE(4) tertile when compared with the lowest (114 vs. 52 episodes per 100 patient-years, P = 0.038). LTE(4) levels are elevated in children with SCD when compared with controls. LTE(4) levels are associated with an increased rate of hospitalizations for pain. Copyright 2008 Wiley-Liss, Inc.

Parental consanguinity and susceptibility to drug abuse among offspring, a case-control study.

PubMed

Saadat, Mostafa; Vakili-Ghartavol, Roghayyeh

2010-11-30

Consanguineous marriage is the union of individuals having at least one common ancestor. It is well established that consanguinity is a potential risk factor for many adverse health outcome of offspring. In the present case-control study we tested the hypothesis of an association between parental consanguinity marriages and risk of offspring substance abuse. The study was performed in Shiraz (Fars province, Iran). Here 156 male drug abusers (case group) and 264 randomly selected healthy blood donors, matched for age and gender as control group, were included in the study. The prevalence of parental consanguineous marriages in the studied sample was 39.1 and 28.0% among cases and controls, respectively. The difference was statistically significant. The substance abusers were more smokers and drinkers compared with the control group. There was significant negative linear trend between drug abuse and level of education. The participants stratified using drinking habits and then the analysis was carried out separately for drinker and non-drinker subjects. Among drinkers, neither before nor after adjusting for smoking status and educational level, parental consanguinity did not show association with risk of substance abuse. Among non-drinkers, after adjusting for smoking status and educational level, parental consanguineous marriage was significantly associated with increased risk of substance abuse. Our study supports a significant relationship between parental consanguinity and drug abuse among non-drinker subjects. Copyright © 2010 Elsevier Ltd. All rights reserved.

The SPINK gene family and celiac disease susceptibility.

PubMed

Wapenaar, Martin C; Monsuur, Alienke J; Poell, Jos; van 't Slot, Ruben; Meijer, Jos W R; Meijer, Gerrit A; Mulder, Chris J; Mearin, Maria Luisa; Wijmenga, Cisca

2007-05-01

The gene family of serine protease inhibitors of the Kazal type (SPINK) are functional and positional candidate genes for celiac disease (CD). Our aim was to assess the gut mucosal gene expression and genetic association of SPINK1, -2, -4, and -5 in the Dutch CD population. Gene expression was determined for all four SPINK genes by quantitative reverse-transcription polymerase chain reaction in duodenal biopsy samples from untreated (n=15) and diet-treated patients (n=31) and controls (n=16). Genetic association of the four SPINK genes was tested within a total of 18 haplotype tagging SNPs, one coding SNP, 310 patients, and 180 controls. The SPINK4 study cohort was further expanded to include 479 CD cases and 540 controls. SPINK4 DNA sequence analysis was performed on six members of a multigeneration CD family to detect possible point mutations or deletions. SPINK4 showed differential gene expression, which was at its highest in untreated patients and dropped sharply upon commencement of a gluten-free diet. Genetic association tests for all four SPINK genes were negative, including SPINK4 in the extended case/control cohort. No SPINK4 mutations or deletions were observed in the multigeneration CD family with linkage to chromosome 9p21-13 nor was the coding SNP disease-specific. SPINK4 exhibits CD pathology-related differential gene expression, likely derived from altered goblet cell activity. All of the four SPINK genes tested do not contribute to the genetic risk for CD in the Dutch population.

Polymorphisms in CTNNBL1 in relation to colorectal cancer with evolutionary implications

PubMed Central

Huhn, Stefanie; Ingelfinger, Dierk; Bermejo, Justo Lorenzo; Bevier, Melanie; Pardini, Barbara; Naccarati, Alessio; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Pox, Christian P; Goecke, Timm; Kloor, Matthias; Loeffler, Markus; Büttner, Reinhard; Vodickova, Ludmila; Novotny, Jan; Demir, Kubilay; Cruciat, Cristina-Maria; Renneberg, Rebecca; Huber, Wolfgang; Niehrs, Christof; Boutros, Michael; Propping, Peter; Vodička, Pavel; Hemminki, Kari; Försti, Asta

2011-01-01

Colorectal cancer (CRC) is a complex disease related to environmental and genetic risk factors. Several studies have shown that susceptibility to complex diseases can be mediated by ancestral alleles. Using RNAi screening, CTNNBL1 was identified as a putative regulator of the Wnt signaling pathway, which plays a key role in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in CTNNBL1 have been associated with obesity, a known risk factor for CRC. We investigated whether genetic variation in CTNNBL1 affects susceptibility to CRC and tested for signals of recent selection. We applied a tagging SNP approach that cover all known common variation in CTNNBL1 (allele frequency >5%; r2>0.8). A case-control study was carried out using two well-characterized study populations: a hospital-based Czech population composed of 751 sporadic cases and 755 controls and a family/early onset-based German population (697 cases and 644 controls). Genotyping was performed using allele specific PCR based TaqMan® assays (Applied Biosystems, Weiterstadt, Germany). In the Czech cohort, containing sporadic cases, the ancestral alleles of three SNPs showed evidence of association with CRC: rs2344481 (OR 1.44, 95%CI 1.06-1.95, dominant model), rs2281148 (OR 0.59, 95%CI 0.36-0.96, dominant model) and rs2235460 (OR 1.38, 95%CI 1.01-1.89, AA vs. GG). The associations were less prominent in the family/early onset-based German cohort. Data derived from several databases and statistical tests consistently pointed to a likely shaping of CTNNBL1 by positive selection. Further studies are needed to identify the actual function of CTNNBL1 and to validate the association results in other populations. PMID:21537400

Genetic moderators and psychiatric mediators of the link between sexual abuse and alcohol dependence.

PubMed

Copeland, William E; Magnusson, Asa; Göransson, Mona; Heilig, Markus A

2011-06-01

This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that might affect treatment planning. A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Genetic Moderators and Psychiatric Mediators of the link between Sexual Abuse and Alcohol Dependence

PubMed Central

Copeland, William E.; Magnusson, Åsa; Göransson, Mona; Heilig, Markus A.

2011-01-01

Background/Objective This study used a case-control female sample to test psychiatric mediators and genetic moderators of the effect of sexual abuse on later alcohol dependence. The study also tested differences between alcohol dependent women with or without a history of sexual abuse on variables that that might affect treatment planning. Methods A case-control design compared 192 treatment-seeking alcohol dependent women with 177 healthy population controls. All participants were assessed for alcohol-related behaviors, sexual abuse history, psychiatric problems, and personality functioning. Markers were genotyped in the CRHR1, MAO-A and OPRM1 genes. Results The association of sexual abuse with alcohol dependence was limited to the most severe category of sexual abuse involving anal or vaginal penetration. Of the five psychiatric disorders tested, anxiety, anorexia nervosa, and bulimia met criteria as potential mediators of the abuse-alcohol dependence association. Severe sexual abuse continued to have an independent effect on alcohol dependence status even after accounting for these potential mediators. None of the candidate genetic markers moderated the association between sexual abuse and alcohol dependence. Of alcohol dependent participants, those with a history of severe abuse rated higher on alcoholism severity, and psychiatric comorbidities. Conclusion Sexual abuse is associated with later alcohol problems directly as well as through its effect on psychiatric problems. Treatment-seeking alcohol dependent women with a history of abuse have distinct features as compared to other alcohol dependent women. PMID:21193270

Comprehensive association analysis of 27 genes from the GABAergic system in Japanese individuals affected with schizophrenia.

PubMed

Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo

2017-07-01

Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA A receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA A receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P allele =0.002; uncorrected) and rs1157122 (P allele =0.006; uncorrected) showed top hits, followed by rs723432 (P allele =0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.

Aseptic meningitis outbreak associated with echovirus 30 among high school football players--Los Angeles County, California, 2014.

PubMed

Croker, Curtis; Civen, Rachel; Keough, Kathleen; Ngo, Van; Marutani, Amy; Schwartz, Benjamin

2015-01-02

On August 4, 2014, the Acute Communicable Disease Control Program of the Los Angeles County Department of Public Health received a report of three aseptic meningitis cases among football players at a county high school. An investigation was conducted to determine the extent of the outbreak, identify potential exposures, and recommend control measures. An outbreak-associated aseptic meningitis case was defined as an illness of any team or family member with onset during July 28-August 11 with 1) cerebrospinal fluid pleocytosis and negative bacterial culture or 2) an emergency department visit with headache, fever, and stiff neck. Ten cases were identified; nine in males, and one in a female; patient ages ranged from 13 to 17 years. All the patients sought care at an emergency department, and five were hospitalized, resulting in 12 total hospital days. All 10 patients have recovered. Eight patients were football players, and two were siblings of football players. The most affected subgroup was the junior varsity football team, with seven cases out of 57 players (attack rate = 12.3%); the relative risk for aseptic meningitis was higher among players who were linemen than among those who were not linemen (relative risk = 5.4 [p = 0.03]). Of the 10 patients, eight tested positive by polymerase chain reaction for enterovirus, and two were not tested. Echovirus testing was performed at the California Viral and Rickettsial Disease Laboratory. Of the eight specimens testing positive for enterovirus, seven tested positive for echovirus 30, and one specimen could not be typed because of insufficient quantity.

Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

PubMed

Park, Jong-Moo; Cho, Yong-Jin; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Han, Moon-Ku; Ko, Youngchai; Lee, Jun; Cha, Jae-Kwan; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

2014-01-01

This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population.

PubMed

Cai, Lei; Chen, Tianlu; Yang, Jinglei; Zhou, Kejun; Yan, Xiaomei; Chen, Wenzhong; Sun, Liya; Li, Linlin; Qin, Shengying; Wang, Peng; Yang, Ping; Cui, Donghong; Burmeister, Margit; He, Lin; Jia, Wei; Wan, Chunling

2015-10-12

Little is known about the trace element profile differences between Schizophrenia patients and healthy controls; previous studies about the association of certain elements with Schizophrenia have obtained conflicting results. To identify these differences in the Han Chinese population, inductively coupled plasma-mass spectrometry was used to quantify the levels of 35 elements in the sera of 111 Schizophrenia patients and 110 healthy participants, which consisted of a training (61/61 for cases/controls included) and a test group including remaining participants. An orthogonal projection to latent structures model was constructed from the training group (R(2)Y = 0.465, Q(2)cum = 0.343) had a sensitivity of 76.0% and a specificity of 71.4% in the test group. Single element analysis indicated that the concentrations of cesium, zinc, and selenium were significantly reduced in patients with Schizophrenia in both the training and test groups. The meta-analysis including 522 cases and 360 controls supported that Zinc was significantly associated with Schizophrenia (standardized mean difference [SMD], -0.81; 95% confidence intervals [CI], -1.46 to -0.16, P = 0.01) in the random-effect model. Information theory analysis indicated that Zinc could play roles independently in Schizophrenia. These results suggest clear element profile differences between patients with Schizophrenia and healthy controls, and reduced Zn level is confirmed in the Schizophrenia patients.

Possible roles of bilirubin and breast milk in protection against retinopathy of prematurity.

PubMed

Kao, Joanna S; Dawson, Jeffrey D; Murray, Jeffrey C; Dagle, John M; Berends, Susan K; Gillen, Susan B; Bell, Edward F

2011-03-01

To explore the association of serum bilirubin level and breast milk feeding with retinopathy of prematurity (ROP) in preterm infants. We conducted a case-control study to examine the independent and combined effects of serum bilirubin and breast milk feeding on ROP risk in infants <32 weeks gestation or with birth weight <1500 g. Cases (66 infants with ROP) were matched with controls (66 infants without ROP) based on factors known to affect ROP risk. When analysed using the paired t-test, the peak bilirubin levels were lower in ROP cases than in controls (mean 7.2 vs. 7.9 mg/dL; p = 0.045). Using conditional logistic regression, we found a negative association between highest serum bilirubin level and risk of ROP (OR = 0.82 per 1-mg/dL change in bilirubin; p = 0.06). There was no significant association between breast milk feeding and risk of ROP. Bilirubin may help to protect preterm infants against ROP. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

A prolonged, community-wide cholera outbreak associated with drinking water contaminated by sewage in Kasese District, western Uganda.

PubMed

Kwesiga, Benon; Pande, Gerald; Ario, Alex Riolexus; Tumwesigye, Nazarius Mbona; Matovu, Joseph K B; Zhu, Bao-Ping

2017-07-18

In May 2015, a cholera outbreak that had lasted 3 months and infected over 100 people was reported in Kasese District, Uganda, where multiple cholera outbreaks had occurred previously. We conducted an investigation to identify the mode of transmission to guide control measures. We defined a suspected case as onset of acute watery diarrhoea from 1 February 2015 onwards in a Kasese resident. A confirmed case was a suspected case with Vibrio cholerae O1 El Tor, serotype Inaba cultured from a stool sample. We reviewed medical records to find cases. We conducted a case-control study to compare exposures among confirmed case-persons and asymptomatic controls, matched by village and age-group. We conducted environmental assessments. We tested water samples from the most affected area for total coliforms using the Most Probable Number (MPN) method. We identified 183 suspected cases including 61 confirmed cases of Vibrio cholerae 01; serotype Inaba, with onset between February and July 2015. 2 case-persons died of cholera. The outbreak occurred in 80 villages and affected all age groups; the highest attack rate occurred in the 5-14 year age group (4.1/10,000). The outbreak started in Bwera Sub-County bordering the Democratic Republic of Congo and spread eastward through sustained community transmission. The first case-persons were involved in cross-border trading. The case-control study, which involved 49 confirmed cases and 201 controls, showed that 94% (46/49) of case-persons compared with 79% (160/201) of control-persons drank water without boiling or treatment (OR M-H =4.8, 95% CI: 1.3-18). Water collected from the two main sources, i.e., public pipes (consumed by 39% of case-persons and 38% of control-persons) or streams (consumed by 29% of case-persons and 24% control-persons) had high coliform counts, a marker of faecal contamination. Environmental assessment revealed evidence of open defecation along the streams. No food items were significantly associated with illness. This prolonged, community-wide cholera outbreak was associated with drinking water contaminated by faecal matter and cross-border trading. We recommended rigorous disposal of patients' faeces, chlorination of piped water, and boiling or treatment of drinking water. The outbreak stopped 6 weeks after these recommendations were implemented.

Toxocara canis infection of children: epidemiologic and neuropsychologic findings.

PubMed Central

Marmor, M; Glickman, L; Shofer, F; Faich, L A; Rosenberg, C; Cornblatt, B; Friedman, S

1987-01-01

Sera from 4,652 children whose blood was submitted to the New York City Department of Health for lead analysis were tested for antibodies to Toxocara canis using an enzyme-linked immunosorbent assay (ELISA). Standardized to the age distribution of the study population, T. canis seropositivity (inverse titers greater than or equal to 16) was 5.7 per cent in males and 5.1 per cent in females. T. canis antibody titers and lead exposures as measured by Centers for Disease Control lead classes were positively correlated. Children who were seropositive to T. canis (cases) were compared to seronegatives (controls) matched on age (+/- 6 months), sex, time-of-screening (+/- 3 months) and CDC lead class. Logistic regression analysis of 155 case-control pairs demonstrated elevated relative risks (RRs) for geophagia (RR = 3.14; 95% CI = 1.75, 5.64) and having had a litter of puppies in the home (RR = 5.22; 95% CI = 1.63, 16.71). Compared to controls, cases had increased eosinophil counts, serum immunoglobulin E concentrations, and anti-hemagglutinin-A titers. Small deficits in cases compared to controls were found in performance on several neuropsychological tests after adjustment for potential confounders including case-control differences in race, socioeconomic status, and current blood lead concentrations. The study thus confirmed that T. canis infection is common in urban children and suggested that infection may be associated with adverse neuropsychological effects. PMID:3565646

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

PubMed

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Marchand, Loïc Le; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2011-10-30

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

Cytokine levels as biomarkers of radiation fibrosis in patients treated with breast radiotherapy

PubMed Central

2014-01-01

Background Radiation fibrosis is not easily measurable although clinical scores have been developed for this purpose. Biomarkers present an alternative more objective approach to quantification, and estimation in blood provides accessible samples. We investigated if blood cytokines could be used to measure established fibrosis in patients who have undergone radiotherapy for breast cancer. Methods We studied two cohorts treated by breast-conserving surgery and radiotherapy in the UK START Trial A, one with breast fibrosis (cases) and one with no or minimal fibrosis (controls). Two candidate cytokines, plasma connective tissue growth factor (CTGF) and serum interleukin-6 (IL6) were estimated by ELISA. Comparisons between cases and controls used the t-test or Mann–Whitney test and associations between blood concentration and clinical factors were assessed using the Spearman rank correlation coefficient. Results Seventy patients were included (26 cases, 44 controls). Mean time since radiotherapy was 9.9 years (range 8.3-12.0). No statistically significant differences between cases and controls in serum IL6 (median (IQR) 0.84 pg/ml (0.57-1.14), 0.75 pg/ml (0.41-1.43) respectively) or plasma CTGF (331.4 pg/ml (234.8-602.9), 334.5 pg/ml (270.0-452.8) were identified. There were no significant associations between blood cytokine concentration and age, fibrosis severity, breast size or time since radiotherapy. Conclusions No significant difference in IL6 or CTGF concentrations was detected between patients with breast fibrosis and controls with minimal or no fibrosis. PMID:24885397

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

PubMed

Browning, B L; Annese, V; Barclay, M L; Bingham, S A; Brand, S; Büning, C; Castro, M; Cucchiara, S; Dallapiccola, B; Drummond, H; Ferguson, L R; Ferraris, A; Fisher, S A; Gearry, R B; Glas, J; Henckaerts, L; Huebner, C; Knafelz, D; Lakatos, L; Lakatos, P L; Latiano, A; Liu, X; Mathew, C; Müller-Myhsok, B; Newman, W G; Nimmo, E R; Noble, C L; Palmieri, O; Parkes, M; Petermann, I; Rutgeerts, P; Satsangi, J; Shelling, A N; Siminovitch, K A; Török, H-P; Tremelling, M; Vermeire, S; Valvano, M R; Witt, H

2008-01-01

DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. DLG5 30Q is associated with a small reduction in risk of CD in women.

Pesticide exposure and lymphohaematopoietic cancers: a case-control study in an agricultural region (Larissa, Thessaly, Greece)

PubMed Central

2011-01-01

Background The causality of lymphohaematopoietic cancers (LHC) is multifactorial and studies investigating the association between chemical exposure and LHC have produced variable results. The aim of this study was to investigate the relationships between exposure to pesticides and LHC in an agricultural region of Greece. Methods A structured questionnaire was employed in a hospital-based case control study to gather information on demographics, occupation, exposure to pesticides, agricultural practices, family and medical history and smoking. To control for confounders, backward conditional and multinomial logistic regression analyses were used. To assess the dose-response relationship between exposure and disease, the chi-square test for trend was used. Results Three hundred and fifty-four (354) histologically confirmed LHC cases diagnosed from 2004 to 2006 and 455 sex- and age-matched controls were included in the study. Pesticide exposure was associated with total LHC cases (OR 1.46, 95% CI 1.05-2.04), myelodysplastic syndrome (MDS) (OR 1.87, 95% CI 1.00-3.51) and leukaemia (OR 2.14, 95% CI 1.09-4.20). A dose-response pattern was observed for total LHC cases (P = 0.004), MDS (P = 0.024) and leukaemia (P = 0.002). Pesticide exposure was independently associated with total LHC cases (OR 1.41, 95% CI 1.00 - 2.00) and leukaemia (OR 2.05, 95% CI 1.02-4.12) after controlling for age, smoking and family history (cancers, LHC and immunological disorders). Smoking during application of pesticides was strongly associated with total LHC cases (OR 3.29, 95% CI 1.81-5.98), MDS (OR 3.67, 95% CI 1.18-12.11), leukaemia (OR 10.15, 95% CI 2.15-65.69) and lymphoma (OR 2.72, 95% CI 1.02-8.00). This association was even stronger for total LHC cases (OR 18.18, 95% CI 2.38-381.17) when eating simultaneously with pesticide application. Conclusions Lymphohaematopoietic cancers were associated with pesticide exposure after controlling for confounders. Smoking and eating during pesticide application were identified as modifying factors increasing the risk for LHC. The poor pesticide work practices identified during this study underline the need for educational campaigns for farmers. PMID:21205298

Fine mapping of the chromosome 10q11-q21 linkage region in Alzheimer's disease cases and controls.

PubMed

Fallin, Margaret Daniele; Szymanski, Megan; Wang, Ruihua; Gherman, Adrian; Bassett, Susan S; Avramopoulos, Dimitrios

2010-07-01

We have previously reported strong linkage on chromosome 10q in pedigrees transmitting Alzheimer's disease through the mother, overlapping with many significant linkage reports including the largest reported study. Here, we report the most comprehensive fine mapping of this region to date. In a sample of 638 late-onset Alzheimer's disease (LOAD) cases and controls including 104 maternal LOAD cases, we genotyped 3,884 single nucleotide polymorphisms (SNPs) covering 15.2 Mb. We then used imputations and publicly available data to generate an extended dataset including 4,329 SNPs for 1,209 AD cases and 839 controls in the same region. Further, we screened eight genes in this region for rare alleles in 283 individuals by nucleotide sequencing, and we tested for possible monoallelic expression as it might underlie our maternal parent of origin linkage. We excluded the possibility of multiple rare coding risk variants for these genes and monoallelic expression when we could test for it. One SNP, rs10824310 in the PRKG1 gene, showed study-wide significant association without a parent of origin effect, but the effect size estimate is not of sufficient magnitude to explain the linkage, and no association is observed in an independent genome-wide association studies (GWAS) report. Further, no causative variants were identified though sequencing. Analysis of cases with maternal disease origin pointed to a few regions of interest that included the genes PRKG1 and PCDH15 and an intergenic interval of 200 Kb. It is likely that non-transcribed rare variants or other mechanisms involving these genomic regions underlie the observed linkage and parent of origin effect. Acquiring additional support and clarifying the mechanisms of such involvement is important for AD and other complex disorder genetics research.

Systemic Lupus Erythematosus is Associated with Uranium Exposure in a Community Living Near a Uranium Processing Plant: A Nested Case-Control Study

PubMed Central

Lu-Fritts, Pai-Yue; Kottyan, Leah C.; James, Judith A.; Xie, Changchung; Buckholz, Jeanette M.; Pinney, Susan M.; Harley, John B.

2014-01-01

Objective Explore the hypothesis that cases of SLE will be found more frequently in community members with high prior uranium exposure in the Fernald Community Cohort (FCC). Methods A nested case control study was performed. The FCC is a volunteer population that lived near a uranium ore processing plant in Fernald, Ohio, USA during plant operation and members were monitored for 18 years. Uranium plant workers were excluded. SLE cases were identified using American College of Rheumatology classification criteria, laboratory testing, and medical record review. Each case was matched to four age-, race-, and sex-matched controls. Sera from potential cases and controls were screened for autoantibodies. Cumulative uranium particulate exposure was calculated using a dosimetry model. Logistic regression with covariates was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Results The FCC includes 4,187 individuals with background uranium exposure, 1,273 with moderate exposure, and 2,756 with higher exposure. SLE was confirmed in 23 of 31 individuals with a lupus ICD9 code, and in 2 of 43 other individuals prescribed hydroxychloroquine. The female:male ratio was 5.25:1. Of the 25 SLE cases, 12 were in the higher exposure group. SLE was associated with higher uranium exposure (OR 3.92, 95% CI 1.131-13.588, p = 0.031). Conclusion High uranium exposure is associated with SLE relative to matched controls in this sample of uranium exposed individuals. Potential explanations for this relationship include possible autoimmune or estrogen effects of uranium, somatic mutation, epigenetic effects, or effects of some other unidentified accompanying exposure. PMID:25103365

Patterns of Migration and Risks Associated with Leprosy among Migrants in Maranhão, Brazil

PubMed Central

Murto, Christine; Chammartin, Frédérique; Schwarz, Karolin; da Costa, Lea Marcia Melo; Kaplan, Charles; Heukelbach, Jorg

2013-01-01

Leprosy remains a public health problem in Brazil with new case incidence exceeding World Health Organization (WHO) goals in endemic clusters throughout the country. Migration can facilitate movement of disease between endemic and non-endemic areas, and has been considered a possible factor in continued leprosy incidence in Brazil. A study was conducted to investigate migration as a risk factor for leprosy. The study had three aims: (1) examine past five year migration as a risk factor for leprosy, (2) describe and compare geographic and temporal patterns of migration among past 5-year migrants with leprosy and a control group, and (3) examine social determinants of health associated with leprosy among past 5-year migrants. The study implemented a matched case-control design and analysis comparing individuals newly diagnosed with leprosy (n = 340) and a clinically unapparent control group (n = 340) without clinical signs of leprosy, matched for age, sex and location in four endemic municipalities in the state of Maranhão, northeastern Brazil. Fishers exact test was used to conduct bivariate analyses. A multivariate logistic regression analysis was employed to control for possible confounding variables. Eighty cases (23.5%) migrated 5-years prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the corresponding case diagnosis. Past 5 year migration was found to be associated with leprosy (OR: 1.59; 95% CI 1.07–2.38; p = 0.02), and remained significantly associated with leprosy after controlling for leprosy contact in the family, household, and family/household contact. Poverty, as well as leprosy contact in the family, household and other leprosy contact, was associated with leprosy among past 5-year migrants in the bivariate analysis. Alcohol consumption was also associated with leprosy, a relevant risk factor in susceptibility to infection that should be explored in future research. Our findings provide insight into patterns of migration to localize focused control efforts in endemic areas with high population mobility. PMID:24040433

Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation.

PubMed

Atchison, Christie M; Amankwah, Ernest; Wilhelm, Jean; Arlikar, Shilpa; Branchford, Brian R; Stock, Arabela; Streiff, Michael; Takemoto, Clifford; Ayala, Irmel; Everett, Allen; Stapleton, Gary; Jacobs, Marshall L; Jacobs, Jeffrey P; Goldenberg, Neil A

2018-02-01

Paediatric hospital-associated venous thromboembolism is a leading quality and safety concern at children's hospitals. The aim of this study was to determine risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. We conducted a retrospective, case-control study of children admitted to the cardiovascular intensive care unit at Johns Hopkins All Children's Hospital (St. Petersburg, Florida, United States of America) from 2006 to 2013. Hospital-associated venous thromboembolism cases were identified based on ICD-9 discharge codes and validated using radiological record review. We randomly selected two contemporaneous cardiovascular intensive care unit controls without hospital-associated venous thromboembolism for each hospital-associated venous thromboembolism case, and limited the study population to patients who had undergone cardiothoracic surgery or therapeutic cardiac catheterisation. Odds ratios and 95% confidence intervals for associations between putative risk factors and hospital-associated venous thromboembolism were determined using univariate and multivariate logistic regression. Among 2718 admissions to the cardiovascular intensive care unit during the study period, 65 met the criteria for hospital-associated venous thromboembolism (occurrence rate, 2%). Restriction to cases and controls having undergone the procedures of interest yielded a final study population of 57 hospital-associated venous thromboembolism cases and 76 controls. In a multiple logistic regression model, major infection (odds ratio=5.77, 95% confidence interval=1.06-31.4), age ⩽1 year (odds ratio=6.75, 95% confidence interval=1.13-160), and central venous catheterisation (odds ratio=7.36, 95% confidence interval=1.13-47.8) were found to be statistically significant independent risk factors for hospital-associated venous thromboembolism in these children. Patients with all three factors had a markedly increased post-test probability of having hospital-associated venous thromboembolism. Major infection, infancy, and central venous catheterisation are independent risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or cardiac catheter-based intervention, which, in combination, define a high-risk group for hospital-associated venous thromboembolism.

Comparison of two control groups for estimation of oral cholera vaccine effectiveness using a case-control study design.

PubMed

Franke, Molly F; Jerome, J Gregory; Matias, Wilfredo R; Ternier, Ralph; Hilaire, Isabelle J; Harris, Jason B; Ivers, Louise C

2017-10-13

Case-control studies to quantify oral cholera vaccine effectiveness (VE) often rely on neighbors without diarrhea as community controls. Test-negative controls can be easily recruited and may minimize bias due to differential health-seeking behavior and recall. We compared VE estimates derived from community and test-negative controls and conducted bias-indicator analyses to assess potential bias with community controls. From October 2012 through November 2016, patients with acute watery diarrhea were recruited from cholera treatment centers in rural Haiti. Cholera cases had a positive stool culture. Non-cholera diarrhea cases (test-negative controls and non-cholera diarrhea cases for bias-indicator analyses) had a negative culture and rapid test. Up to four community controls were matched to diarrhea cases by age group, time, and neighborhood. Primary analyses included 181 cholera cases, 157 non-cholera diarrhea cases, 716 VE community controls and 625 bias-indicator community controls. VE for self-reported vaccination with two doses was consistent across the two control groups, with statistically significant VE estimates ranging from 72 to 74%. Sensitivity analyses revealed similar, though somewhat attenuated estimates for self-reported two dose VE. Bias-indicator estimates were consistently less than one, with VE estimates ranging from 19 to 43%, some of which were statistically significant. OCV estimates from case-control analyses using community and test-negative controls were similar. While bias-indicator analyses suggested possible over-estimation of VE estimates using community controls, test-negative analyses suggested this bias, if present, was minimal. Test-negative controls can be a valid low-cost and time-efficient alternative to community controls for OCV effectiveness estimation and may be especially relevant in emergency situations. Copyright © 2017. Published by Elsevier Ltd.

The influence of hepatitis B and C virus coinfection on liver histopathology in children.

PubMed

Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Walewska-Zielecka, Bożena; Marczyńska, Magdalena

2015-03-01

The influence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection on liver histology in children remains unknown. We analyzed histopathological features in 70 treatment-naïve children: 10 with HBV/HCV coinfection (case group A), 30 with HBV (control group B), and 30 with HCV (control group C). Liver biopsies were scored for grading and staging according to Knodell's modified system and were tested for an association with demographic and laboratory data. The mean grade was higher in coinfected children compared to control group C (6.2 ± 3.0 vs. 4.2 ± 2.5, p = 0.04), but not control group B (p = 0.47). A higher proportion of patients with moderate to severe necroinflammation were observed in case group A compared to isolated HCV (p = 0.05). Mean staging did not differ between the case and control groups. Multivariate analysis revealed that HBV/HCV coinfection and aminotransferase activity were independently associated with moderate to severe necroinflammatory activity Conclusion: HBV/HCV coinfection was associated with moderate to severe necroinflammation irrespective of age at biopsy or duration of infection and led to significantly higher necroinflammatory activity than HCV monoinfection. HBV/HCV coinfection did not enhance fibrosis. High aminotransferase levels were positively associated with moderate to severe necroinflammation.

Ear Infection in Isolated Cleft Lip: Etiological Implications.

PubMed

Ruegg, Teresa A; Cooper, Margaret E; Leslie, Elizabeth J; Ford, Matthew D; Wehby, George L; Deleyiannis, Frederic W B; Czeizel, Andrew E; Hecht, Jacqueline T; Marazita, Mary L; Weinberg, Seth M

2017-03-01

  Chronic ear infections are a common occurrence in children with orofacial clefts involving the secondary palate. Less is known about the middle ear status of individuals with isolated clefts of the lip, although several studies have reported elevated rates of ear infection in this group. The purpose of this retrospective study was to test the hypothesis that chronic ear infections occur more frequently in isolated cleft lip cases (n = 94) compared with controls (n = 183).   A questionnaire was used to obtain information on history of chronic ear infection. The association between ear infection status (present/absent) and cleft lip status (cleft lip case/control) was tested using both chi-square and logistic regression.   The reported occurrence of chronic ear infection was significantly greater in cleft lip cases (31%) compared with unaffected controls (11%). After adjusting for age and sex, having a cleft lip increased the odds of being positive for ear infection by a factor greater than 3 (odds ratio = 3.698; 95% confidence interval = 1.91 to 7.14). Within cleft lip cases, there was no difference in the occurrence of ear infection by defect laterality or by the type of clefting present in the family history. Although velopharyngeal insufficiency was present in 18.4% of our cleft lip sample, there was no statistical association between ear infection and abnormal speech patterns. These results may have potential implications both for the clinical management of isolated cleft lip cases and for understanding the etiology of orofacial clefting.

Mediation analysis of alcohol consumption, DNA methylation, and epithelial ovarian cancer.

PubMed

Wu, Dongyan; Yang, Haitao; Winham, Stacey J; Natanzon, Yanina; Koestler, Devin C; Luo, Tiane; Fridley, Brooke L; Goode, Ellen L; Zhang, Yanbo; Cui, Yuehua

2018-03-01

Epigenetic factors and consumption of alcohol, which suppresses DNA methylation, may influence the development and progression of epithelial ovarian cancer (EOC). However, there is a lack of understanding whether these factors interact to affect the EOC risk. In this study, we aimed to gain insight into this relationship by identifying leukocyte-derived DNA methylation markers acting as potential mediators of alcohol-associated EOC. We implemented a causal inference test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to examine CpG sites that mediate the association between alcohol consumption and EOC risk. We modified one step of the CIT by adopting a high-dimensional inference procedure. The data were based on 196 cases and 202 age-matched controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent potential mediators of the relationship between alcohol consumption and EOC case-control status. Implementation of the VanderWeele and Vansteelandt multiple mediator model further revealed that these two CpGs were the key mediators. Decreased methylation at both CpGs was more common in cases who drank alcohol at the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which has been previously shown to be overexpressed in EOC. These findings suggest two CpGs may serve as novel biomarkers for EOC susceptibility.

Fasting urinary calcium-to-creatinine and oxalate-to-creatinine ratios in dogs with calcium oxalate urolithiasis and breed-matched controls.

PubMed

Furrow, E; Patterson, E E; Armstrong, P J; Osborne, C A; Lulich, J P

2015-01-01

Hypercalciuria and hyperoxaluria are risk factors for calcium oxalate (CaOx) urolithiasis, but breed-specific reports of urinary metabolites and their relationship with stone status are lacking. To compare urinary metabolites (calcium and oxalate) and blood ionized calcium (iCa) concentrations between CaOx stone formers and breed-matched stone-free controls for the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. Forty-seven Miniature Schnauzers (23 cases and 24 controls), 27 Bichons Frise (14 cases and 13 controls), and 15 Shih Tzus (7 cases and 8 controls). Prospective study. Fasting spot urinary calcium-to-creatinine and oxalate-to-creatinine ratios (UCa/Cr and UOx/Cr, respectively) and blood iCa concentrations were measured and compared between cases and controls within and across breeds. Regression models were used to test the effect of patient and environmental factors on these variables. UCa/Cr was higher in cases than controls for each of the 3 breeds. In addition to stone status, being on a therapeutic food designed to prevent CaOx stone recurrence was associated with higher UCa/Cr. UOx/Cr did not differ between cases and controls for any of the breeds. Blood iCa was higher in cases than controls in the Miniature Schnauzer and Bichon Frise breeds and had a moderate correlation with UCa/Cr. Hypercalciuria is associated with CaOx stone status in the Miniature Schnauzer, Bichon Frise, and Shih Tzu breeds. UOx/Cr did not correlate with stone status in these 3 breeds. These findings may influence breed-specific stone prevention recommendations. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Vitamin D deficiency in first episode psychosis: a case-control study.

PubMed

Crews, Matthieu; Lally, John; Gardner-Sood, Poonam; Howes, Oliver; Bonaccorso, Stefania; Smith, Shubulade; Murray, Robin M; Di Forti, Marta; Gaughran, Fiona

2013-11-01

Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP). We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using student's-t tests, paired t-tests and odds ratios for further analysis. Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827). We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies. © 2013 Elsevier B.V. All rights reserved.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case–Control Data?

PubMed Central

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case–control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case–control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case–control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls. PMID:29552553

Impulse-Control Disorders in Parkinson's Disease: A Meta-Analysis and Review of Case-Control Studies.

PubMed

Molde, Helge; Moussavi, Yasaman; Kopperud, Stine Therese; Erga, Aleksander Hagen; Hansen, Anita Lill; Pallesen, Ståle

2018-01-01

Although several case-control studies on the prevalence of Impulse-Control Disorders (ICDs) in Parkinson's Disease (PD) have been conducted, no meta-analytic study on this topic has previously been published. Thus, knowledge about the overall prevalence rate of ICD in PD and factors that might moderate this relationship is lacking. Prevalence studies of ICDs in PD were identified by computer searches in the MEDLINE, PsycINFO, and Web of Science databases, covering the period from January 2000 to February 2017. Data for N  = 4,539, consisting of 2,371 PD patients and 2,168 healthy controls, representing 14 case-control studies were included. Estimation of the odds ratio ( OR ) of ICDs in PD compared to healthy controls was conducted using random-effects models. Mixed-effects models were applied in the moderator analysis of heterogeneity. Publication bias was estimated using a contour-enhanced funnel plot, the Rüker's test, and fail-safe N test for estimating the number of potential missing studies. Overall, the results showed significantly higher ratios for several ICDs in PD compared to healthy controls with the estimated overall OR s ranging between 2.07, 95% CI [1.26, 3.48], for having any ICDs, and 4.26, 95% CI [2.17, 8.36], for hypersexuality. However, the random-effects results for shopping were non-significant, though the fixed-effects model was significant ( OR  = 1.66, 95%CI [1.21, 2.27]). The testing of potential moderator variables of heterogeneity identified the following two variables that were both associated with increased risk: being medically treated for PD and disease duration. The results must be interpreted with some caution due to possible small-studies effect or publication bias. Individuals with PD seem to have a significantly greater risk of suffering from ICDs compared to healthy controls. Gambling, hypersexuality, eating, punding, and hobbying are all ICDs significantly associated with PDs being medically treated for PD.

Escherichia coli O157:H7 outbreak associated with consumption of ground beef, June-July 2002.

PubMed

Vogt, Richard L; Dippold, Laura

2005-01-01

A case-control and environmental study tested the hypothesis that purchasing and eating ground beef from a specific source was the cause of a cluster of cases of hemolytic uremic syndrome (HUS) and Escherichia coli (E. coli) O157:H7 gastroenteritis. A case-control study comparing risk factors was conducted over the telephone on nine case-patients with 23 selected controls. An environmental investigation was conducted that consisted of reviewing beef handling practices at a specific local supermarket and obtaining ground beef samples from the store and two households with case-patients. The analysis of the case-control study showed that eight case-patients (89%) purchased ground beef at Grocery Chain A compared with four controls who did not develop illness (17%) (matched odds ratio=undefined; 95% confidence interval 2.8, infinity; p=0.006). The environmental investigation showed that Grocery Chain A received meat from Meatpacker A. Laboratory analysis of meat samples from Meatpacker A and Grocery Chain A and stool samples from some patients recovered an identical strain of E. coli O157:H7 according to pulse-field gel electrophoresis. Both the case-control and environmental studies showed that purchasing ground beef at Grocery Chain A, which received ground beef from Meatpacker A, was the major risk factor for illness in eight case-patients; the ninth case-patient was found to be unrelated to the outbreak. Furthermore, meat from Meatpacker A was associated with a nationwide outbreak of E. coli O157:H7 illness that resulted in the second largest recall of beef in U.S. history at the time.

The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

PubMed Central

Roura, Esther; Travier, Noémie; Waterboer, Tim; de Sanjosé, Silvia; Bosch, F. Xavier; Pawlita, Michael; Pala, Valeria; Weiderpass, Elisabete; Margall, Núria; Dillner, Joakim; Gram, Inger T.; Tjønneland, Anne; Munk, Christian; Palli, Domenico; Khaw, Kay-Tee; Overvad, Kim; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Fournier, Agnès; Fortner, Renée T.; Ose, Jennifer; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Philippos; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Polidoro, Silvia; Mattiello, Amalia; Lund, Eiliv; Peeters, Petra H.; Bueno-de-Mesquita, H. B(as).; Quirós, J. Ramón; Sánchez, María-José; Navarro, Carmen; Barricarte, Aurelio; Larrañaga, Nerea; Ekström, Johanna; Lindquist, David; Idahl, Annika; Travis, Ruth C.; Merritt, Melissa A.; Gunter, Marc J.; Rinaldi, Sabina; Tommasino, Massimo; Franceschi, Silvia; Riboli, Elio; Castellsagué, Xavier

2016-01-01

Background In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4–0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors. PMID:26808155

SNP rs16906252C>T is an expression and methylation quantitative trait locus associated with an increased risk of developing MGMT-methylated colorectal cancer

PubMed Central

Kuroiwa-Trzmielina, Joice; Wang, Fan; Rapkins, Robert W.; Ward, Robyn L.; Buchanan, Daniel D.; Win, Aung Ko; Clendenning, Mark; Rosty, Christophe; Southey, Melissa C.; Winship, Ingrid M.; Hopper, John L.; Jenkins, Mark A.; Olivier, Jake; Hawkins, Nicholas J.; Hitchins, Megan P.

2016-01-01

Purpose Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter-enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer (CRC) featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. Experimental design By applying a molecular pathological epidemiology case-control study design, associations between rs16906252C>T and risk for CRC overall, and CRC stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of CRC cases and controls. The test sample comprised 1054 CRC cases and 451 controls from Sydney, Australia. The validation sample comprised 612 CRC cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine if rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. Results An association between rs16906252C>T and increased risk of developing MGMT-methylated CRC in the Sydney sample was observed (OR 3.3; 95%CI=2.0–5.3; P<0.0001), which was replicated in the ACCFR sample (OR 4.0; 95%CI=2.4–6.8; P<0.0001). The T allele demonstrated ~2.5-fold reduced transcription in normal colorectal mucosa from cases and controls, and was selectively methylated in a minority of normal cells, indicating rs16906252C>T represents an expression and methylation quantitative trait locus. Conclusions We provide evidence that rs16906252C>T is associated with elevated risk for MGMT-methylated CRC, likely mediated by constitutive epigenetic repression of the T allele. PMID:27267851

The Paraoxonase 1 Gene c.-108C>T SNP in the Promoter Is Associated with Risk for Glioma in Mexican Patients, but Not the p.L55M or p.Q192R Polymorphisms in the Coding Region.

PubMed

González-Herrera, Lizbeth; Gamas-Trujillo, Pablo Alejandro; Medina-Escobedo, Gilberto; Oaxaca-Castillo, David; Pérez-Mendoza, Gerardo; Williams-Jacquez, Dayana; Canto-Cetina, Thelma; Vargas-García, Rubén Darío

2015-09-01

To evaluate the association of the paraoxonase 1 (PON1) gene polymorphisms c.-108C>T, p.L55M, and p.Q192R with the risk of glioma in Southeast Mexico. Decreased PON1 activity caused by polymorphisms has been observed in gliomas, thus supporting the theory that PON1 is involved in tumorigenesis in the brain. Sixty-seven glioma patients and 58 control individuals were included. Three PON1 polymorphisms were genotyped by real-time PCR allelic discrimination using TaqMan probes: c.-108C>T in the promoter region, p.Q192R and p.L55M, both of which were in the coding region. Allele, genotype, and haplotype frequencies were assessed in cases and controls to test for statistical associations (STATA 10.2 package). Significant differences were found for the PON1 c.-108C>T polymorphism between the cases and controls. Compared to the controls the cases were more likely to be CT heterozygous (p =  0.002) or TT homozygous (p = 0.036); similarly cases were more likely to possess a T allele (p = 0.032). In contrast, the p.L55M and p.Q192R polymorphisms did not show significant differences between the glioma cases and controls (p > 0.05). The PON1 c.-108C>T polymorphism in the promoter region is associated with genetic risk for glioma. Conversely, p.L55M and p.Q192R polymorphisms in the coding region do not seem to have an influence in this population.

Association between childhood dimensions of attention deficit hyperactivity disorder and adulthood clinical severity of bipolar disorders.

PubMed

Etain, Bruno; Lajnef, M; Loftus, J; Henry, C; Raust, A; Gard, S; Kahn, J P; Leboyer, M; Scott, J; Bellivier, F

2017-04-01

Clinical features of attention deficit hyperactivity disorder can be frequently observed in cases with bipolar disorders and associated with greater severity of bipolar disorders. Although designed as a screening tool for attention deficit hyperactivity disorder, the Wender Utah Rating Scale could, given its factorial structure, be useful in investigating the early history of impulsive, inattentive or mood-related symptoms among patients with bipolar disorders. We rated the Wender Utah Rating Scale in 276 adult bipolar disorder cases and 228 healthy controls and tested its factorial structure and any associations with bipolar disorder phenomenology. We confirmed a three-factor structure for the Wender Utah Rating Scale (' impulsivity/temper', ' inattentiveness' and ' mood/self-esteem'). Cases and controls differed significantly on Wender Utah Rating Scale total score and sub-scale scores ( p-values < 10 -5 ). About 23% of bipolar disorder cases versus 5% of controls were classified as ' WURS positive' (odds ratio = 5.21 [2.73-9.95]). In bipolar disorders, higher Wender Utah Rating Scale score was associated with earlier age at onset, severity of suicidal behaviors and polysubstance misuse; multivariate analyses, controlling for age and gender, confirmed the associations with age at onset ( p = 0.001) and alcohol and substance misuse ( p = 0.001). Adults with bipolar disorders who reported higher levels of childhood symptoms on the Wender Utah Rating Scale presented a more severe expression of bipolar disorders in terms of age at onset and comorbidity. The Wender Utah Rating Scale could be employed to screen for attention deficit hyperactivity disorder but also for ' at-risk behaviors' in adult bipolar disorder cases and possibly for prodromal signs of early onset in high-risk subjects.

HIV counselling and testing utilisation and attitudes of male inmates in a South African prison.

PubMed

Motshabi, Lelaka C; Pengpid, Supa; Peltzer, Karl

2011-01-01

The Department of Correctional Services Policy on the management of HIV and AIDS for offenders include voluntary counselling and testing (VCT) for HIV as one of the priorities in the rehabilitation of inmates. The aim of this study was to determine factors associated with the utilisation of VCT services in the correctional centres in terms of level of satisfaction, their experiences and expectations, and motivating factors and barriers for VCT utilisation at Losperfontein Correctional Centre, South Africa. This was a case control study (cases being those who underwent testing and controls those who did not) examining predictors of HIV VCT utilisation among 200 male adult sentenced inmates serving medium and maximum sentences. Results indicate that a poor health system (OR=0.34, 95%CI: 0.23 - 0.50) was inversely associated with HIV testing acceptance in prison, while age, educational level, population group, marital status, length of incarceration and access to HIV testing in prison were not associated with HIV testing acceptance in prison. Half of the participants (50%) agreed that VCT services are accessible and are promoted at their correctional centre. Most were satisfied with different components of VCT services, ranging from 79% (fair to very good) for 'the way he/she received you' to 62% 'clarified all your concerns'. This study demonstrated some challenges and benefits to the field of health promotion and HIV prevention in the correctional centres especially with regard to VCT services.

Regional brain volumes and cognition in childhood epilepsy: does size really matter?

PubMed

Zelko, Frank A; Pardoe, Heath R; Blackstone, Sarah R; Jackson, Graeme D; Berg, Anne T

2014-05-01

Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain T1-weighted MRI was obtained and volumes analyzed with FreeSurfer (TM). Total brain volume (TBV) was significantly smaller in cases. After adjustment for TBV, cases had significantly larger regional grey matter volumes for total, frontal, parietal, and precentral cortex. Cases had poorer performance on neurocognitive indices of intelligence and variability of sustained attention. In cases, TBV showed small associations with intellectual indices of verbal and perceptual ability, working memory, and overall IQ. In controls, TBV showed medium associations with working memory and variability of sustained attention. In both groups, small associations were seen between some TBV-adjusted regional brain volumes and neurocognitive indices, but not in a consistent pattern. Brain volume differences did not account for cognitive differences between the groups. Patients with uncomplicated NSE have smaller brains than controls but areas of relative grey matter enlargement. That this relative regional enlargement occurs in the context of poorer overall neurocognitive functioning suggests that it is not adaptive. However, the lack of consistent associations between case-control differences in brain volumes and cognitive functioning suggests that brain volumes have limited explanatory value for cognitive functioning in childhood epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

PTPN22 association in systemic lupus erythematosus (SLE) with respect to individual ancestry and clinical sub-phenotypes.

PubMed

Namjou, Bahram; Kim-Howard, Xana; Sun, Celi; Adler, Adam; Chung, Sharon A; Kaufman, Kenneth M; Kelly, Jennifer A; Glenn, Stuart B; Guthridge, Joel M; Scofield, Robert H; Kimberly, Robert P; Brown, Elizabeth E; Alarcón, Graciela S; Edberg, Jeffrey C; Kim, Jae-Hoon; Choi, Jiyoung; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Boackle, Susan A; Freedman, Barry I; Tsao, Betty P; Langefeld, Carl D; Vyse, Timothy J; Jacob, Chaim O; Pons-Estel, Bernardo; Niewold, Timothy B; Moser Sivils, Kathy L; Merrill, Joan T; Anaya, Juan-Manuel; Gilkeson, Gary S; Gaffney, Patrick M; Bae, Sang-Cheol; Alarcón-Riquelme, Marta E; Harley, John B; Criswell, Lindsey A; James, Judith A; Nath, Swapan K

2013-01-01

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical sub-phenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.7 × 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.7 × 10(-5), OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

PubMed

Easton, Douglas F; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A; Shah, Mitul; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Ahmad, Jamil; Thompson, Ella R; Damiola, Francesca; Pertesi, Maroulio; Voegele, Catherine; Mebirouk, Noura; Robinot, Nivonirina; Durand, Geoffroy; Forey, Nathalie; Luben, Robert N; Ahmed, Shahana; Aittomäki, Kristiina; Anton-Culver, Hoda; Arndt, Volker; Baynes, Caroline; Beckman, Matthias W; Benitez, Javier; Van Den Berg, David; Blot, William J; Bogdanova, Natalia V; Bojesen, Stig E; Brenner, Hermann; Chang-Claude, Jenny; Chia, Kee Seng; Choi, Ji-Yeob; Conroy, Don M; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Fostira, Florentia; García-Closas, Montserrat; Giles, Graham G; Glendon, Gord; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hall, Per; Hart, Steven N; Hartman, Mikael; Hooning, Maartje J; Hsiung, Chia-Ni; Ito, Hidemi; Jakubowska, Anna; James, Paul A; John, Esther M; Johnson, Nichola; Jones, Michael; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lambrechts, Diether; Li, Na; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Meindl, Alfons; Mitchell, Gillian; Muir, Kenneth; Nevelsteen, Ines; van den Ouweland, Ans; Peterlongo, Paolo; Phuah, Sze Yee; Pylkäs, Katri; Rowley, Simone M; Sangrajrang, Suleeporn; Schmutzler, Rita K; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tollenaar, Rob A E M; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine; Verhoef, Senno; Wong-Brown, Michelle; Zheng, Wei; Zheng, Ying; Nevanlinna, Heli; Scott, Rodney J; Andrulis, Irene L; Wu, Anna H; Hopper, John L; Couch, Fergus J; Winqvist, Robert; Burwinkel, Barbara; Sawyer, Elinor J; Schmidt, Marjanka K; Rudolph, Anja; Dörk, Thilo; Brauch, Hiltrud; Hamann, Ute; Neuhausen, Susan L; Milne, Roger L; Fletcher, Olivia; Pharoah, Paul D P; Campbell, Ian G; Dunning, Alison M; Le Calvez-Kelm, Florence; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia

2016-05-01

BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The 5-HTTLPR confers susceptibility to anorexia nervosa in Han Chinese: evidence from a case-control and family-based study.

PubMed

Chen, Jue; Kang, Qing; Jiang, Wenhui; Fan, Juan; Zhang, Mingdao; Yu, Shunying; Zhang, Chen

2015-01-01

Accumulating evidence has implied that serotonin system dysfunction may be involved in the etiology of anorexia nervosa (AN). Serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is the genetic variant coding for the serotonin transporter and has a modulatory effect on its expression. This study aimed to investigate the possible association between the 5-HTTLPR and the susceptibility and severity of AN in Han Chinese using a case-control (255 patients and 351 controls) and family based study (198 trios). Eating disorder examination was used to measure the severity of AN behavioral symptoms. For the case-control study, the 5-HTTLPR showed significant association with AN in our sample (genotypic P = 0.03). The frequency of S allele was significantly higher in patients than that in controls (OR = 1.38, 95%CI: 1.06-1.79, P = 0.017). For the family-based study, the S allele of 5-HTTLPR was preferentially transmitted rather than non-transmitted from the parents to affected offspring (P = 0.013). The results of ANCOVA test revealed no significant association between the 5-HTTLPR polymorphism and severity of AN. Our findings suggested that 5-HTTLPR is able to confer susceptibility to AN in Han Chinese.

A novel vehicle for transmission of Escherichia coli O157:H7 to humans: multistate outbreak of E. coli O157:H7 infections associated with consumption of ready-to-bake commercial prepackaged cookie dough--United States, 2009.

PubMed

Neil, Karen P; Biggerstaff, Gwen; MacDonald, J Kathryn; Trees, Eija; Medus, Carlota; Musser, Kimberlee A; Stroika, Steven G; Zink, Don; Sotir, Mark J

2012-02-15

 Escherichia coli O157:H7 is a Shiga toxin-producing E. coli (STEC) associated with numerous foodborne outbreaks in the United States and is an important cause of bacterial gastrointestinal illness. In May 2009, we investigated a multistate outbreak of E. coli O157:H7 infections.  Outbreak-associated cases were identified using serotyping and molecular subtyping procedures. Traceback investigation and product testing were performed. A matched case-control study was conducted to identify exposures associated with illness using age-, sex-, and state-matched controls.  Seventy-seven patients with illnesses during the period 16 March-8 July 2009 were identified from 30 states; 35 were hospitalized, 10 developed hemolytic-uremic syndrome, and none died. Sixty-six percent of patients were <19 years; 71% were female. In the case-control study, 33 of 35 case patients (94%) consumed ready-to-bake commercial prepackaged cookie dough, compared with 4 of 36 controls (11%) (matched odds ratio = 41.3; P < .001); no other reported exposures were significantly associated with illness. Among case patients consuming cookie dough, 94% reported brand A. Three nonoutbreak STEC strains were isolated from brand A cookie dough. The investigation led to a recall of 3.6 million packages of brand A cookie dough and a product reformulation.  This is the first reported STEC outbreak associated with consuming ready-to-bake commercial prepackaged cookie dough. Despite instructions to bake brand A cookie dough before eating, case patients consumed the product uncooked. Manufacturers should consider formulating ready-to-bake commercial prepackaged cookie dough to be as safe as a ready-to-eat product. More effective consumer education about the risks of eating unbaked cookie dough is needed.

Identifying Etiological Agents Causing Diarrhea in Low Income Ecuadorian Communities

PubMed Central

Vasco, Gabriela; Trueba, Gabriel; Atherton, Richard; Calvopiña, Manuel; Cevallos, William; Andrade, Thamara; Eguiguren, Martha; Eisenberg, Joseph N. S.

2014-01-01

Continued success in decreasing diarrheal disease burden requires targeted interventions. To develop such interventions, it is crucial to understand which pathogens cause diarrhea. Using a case-control design we tested stool samples, collected in both rural and urban Ecuador, for 15 pathogenic microorganisms. Pathogens were present in 51% of case and 27% of control samples from the urban community, and 62% of case and 18% of control samples collected from the rural community. Rotavirus and Shigellae were associated with diarrhea in the urban community; co-infections were more pathogenic than single infection; Campylobacter and Entamoeba histolytica were found in large numbers in cases and controls; and non-typhi Salmonella and enteropathogenic Escherichia coli were not found in any samples. Consistent with the Global Enteric Multicenter Study, focused in south Asia and sub-Saharan Africa, we found that in Ecuador a small group of pathogens accounted for a significant amount of the diarrheal disease burden. PMID:25048373

Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

PubMed Central

Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Ortego-Centeno, Norberto; Ríos, Raquel; Callejas, José Luis; Navarrete, Nuria; García Portales, Rosa; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; Sánchez-Román, Julio; García-Hernández, Francisco José; Castillo, María Jesús; Aguirre, María Ángeles; Gómez-Gracia, Inmaculada; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Vicente, Esther; Andreu, José Luis; Fernández de Castro, Mónica; García de la Peña, Paloma; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Rodríguez Carballeira, Mónica; Narváez, Francisco Javier; Rubio Rivas, Manel; Ortiz Santamaría, Vera; Díaz, Bernardino; Trapiella, Luis; Freire, María del Carmen; Sousa, Adrián; Egurbide, María Victoria; Fanlo Mateo, Patricia; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad; Fernández Sueiro, Luis; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barri J.; Frech, Tracy M.; AlKassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R.D.J.; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier

2014-01-01

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci. PMID:24387989

Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia.

PubMed

Yared, Solomon; Deribe, Kebede; Gebreselassie, Araya; Lemma, Wessenseged; Akililu, Essayas; Kirstein, Oscar D; Balkew, Meshesha; Warburg, Alon; Gebre-Michael, Teshome; Hailu, Asrat

2014-10-14

Visceral leishmaniasis (VL, also called ''kala-azar"), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL. A case-control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL. Elevated odds of VL was associated with goat ownership (OR = 6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR = 6.4; 95% Cl: 1.6-25.6), increased family size (OR = 1.3; 95% Cl: 1.0-1.8) and the number of days spent in the farm field (OR = 1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR = 0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR = 0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR = 0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case. Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission of L. donovani, assess the impact of bed nets and the role of the traditional practice of smoking plants.

Evaluating Reported Candidate Gene Associations with Polycystic Ovary Syndrome

PubMed Central

Pau, Cindy; Saxena, Richa; Welt, Corrine Kolka

2013-01-01

Objective To replicate variants in candidate genes associated with PCOS in a population of European PCOS and control subjects. Design Case-control association analysis and meta-analysis. Setting Major academic hospital Patients Women of European ancestry with PCOS (n=525) and controls (n=472), aged 18 to 45 years. Intervention Variants previously associated with PCOS in candidate gene studies were genotyped (n=39). Metabolic, reproductive and anthropomorphic parameters were examined as a function of the candidate variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. Main Outcome Measure Association of candidate gene variants with PCOS. Results Three variants, rs3797179 (SRD5A1), rs12473543 (POMC), and rs1501299 (ADIPOQ), were nominally associated with PCOS. However, they did not remain significant after correction for multiple testing and none of the variants replicated in a sufficiently powered meta-analysis. Variants in the FBN3 gene (rs17202517 and rs73503752) were associated with smaller waist circumferences and variant rs727428 in the SHBG gene was associated with lower SHBG levels. Conclusion Previously identified variants in candidate genes do not appear to be associated with PCOS risk. PMID:23375202

Socioeconomic Status and Lung Cancer: Unraveling the Contribution of Genetic Admixture

PubMed Central

Selvin, Steve; Wrensch, Margaret R.; Sison, Jennette D.; Hansen, Helen M.; Quesenberry, Charles P.; Seldin, Michael F.; Barcellos, Lisa F.; Buffler, Patricia A.; Wiencke, John K.

2013-01-01

Objectives. We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. Methods. We evaluated SES and genetic ancestry in a Northern California lung cancer case–control study (1998–2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case–control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Results. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Conclusions. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously. PMID:23948011

Hypothyroidism among SLE patients: Case-control study.

PubMed

Watad, Abdulla; Mahroum, Naim; Whitby, Aaron; Gertel, Smadar; Comaneshter, Doron; Cohen, Arnon D; Amital, Howard

2016-05-01

The prevalence of hypothyroidism in SLE patients varies considerably and early reports were mainly based on small cohorts. To investigate the association between SLE and hypothyroidism. Patients with SLE were compared with age and sex-matched controls regarding the proportion of hypothyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. The study included 5018 patients with SLE and 25,090 age and sex-matched controls. The proportion of hypothyroidism in patients with SLE was increased compared with the prevalence in controls (15.58% and 5.75%, respectively, P<0.001). In a multivariate analysis, SLE was associated with hypothyroidism (odds ratio 2.644, 95% confidence interval 2.405-2.908). Patients with SLE have a greater proportion of hypothyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of the possibility of thyroid dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing

PubMed Central

Pharoah, Paul D. P.; Palmieri, Rachel T.; Ramus, Susan J.; Gayther, Simon A.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis C.; Beattie, Mary S.; Beckmann, Matthias W.; Birrer, Michael J.; Bogdanova, Natalia; Bolton, Kelly L.; Brewster, Wendy; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Caldes, Trinidad; Caligo, Maria Adelaide; Campbell, Ian; Chang-Claude, Jenny; Chen, Y. Ann; Chenevix-Trench, Georgia; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Despierre, Evelyn; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Eccles, Diana M.; Ekici, Arif B.; Fasching, Peter A.; de Fazio, Anna; Fenstermacher, David A.; Flanagan, James M.; Fridley, Brooke L.; Friedman, Eitan; Gao, Bo; Gentry-Maharaj, Aleksandra; Godwin, Andrew K.; Goode, Ellen L.; Goodman, Marc T.; Gross, Jenny; Hansen, Thomas V. O.; Harnett, Paul; Heikkinen, Tuomas; Hein, Rebecca; Høgdall, Claus; Høgdall, Estrid; Iversen, Edwin S.; Jakubowska, Anna; Johnatty, Sharon E.; Karlan, Beth Y.; Kauff, Noah D.; Kaye, Stanley B.; Kelemen, Linda E.; Kiemeney, Lambertus A.; Kjaer, Susanne Krüger; Lambrechts, Diether; LaPolla, James P.; Lázaro, Conxi; Le, Nhu D.; Leminen, Arto; Leunen, Karin; Levine, Douglas A.; Lu, Yi; Lundvall, Lene; Macgregor, Stuart; Marees, Tamara; Massuger, Leon F.; McLaughlin, John R.; Menon, Usha; Montagna, Marco; Moysich, Kirsten B.; Narod, Steven A.; Nathanson, Katherine L.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Nickels, Stefan; Osorio, Ana; Paul, Jim; Pearce, Celeste Leigh; Phelan, Catherine M.; Pike, Malcolm C.; Radice, Paolo; Rossing, Mary Anne; Schildkraut, Joellen M.; Sellers, Thomas A.; Singer, Christian F.; Song, Honglin; Stram, Daniel O.; Sutphen, Rebecca; Terry, Kathryn L.; Tsai, Ya-Yu; van Altena, Anne M.; Vergote, Ignace; Vierkant, Robert A.; Vitonis, Allison F.; Walsh, Christine; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wu, Anna H.; Ziogas, Argyrios; Berchuck, Andrew; Risch, Harvey A.

2011-01-01

Purpose An assay for the single nucleotide polymorphism (SNP) rs61764370 has recently been commercially marketed as a clinical test to aid ovarian cancer risk evaluation in women with family histories of the disease. rs67164370 is in a 3′UTR miRNA binding site of the KRAS oncogene, and is a candidate for epithelial ovarian cancer (EOC) susceptibility. However, only one published paper, analyzing fewer than 1,000 subjects in total, has examined this association. Experimental Design Risk association was evaluated in 8,669 cases of invasive EOC and 10,012 controls from nineteen studies participating in the Ovarian Cancer Association Consortium, and in 683 cases and 2,044 controls carrying BRCA1 mutations from studies in the Consortium of Investigators of Modifiers of BRCA1/2. Prognosis association was also examined in a subset of five studies with progression-free survival data and eighteen studies with all-cause mortality data. Results No evidence of association was observed between genotype and risk of unselected EOC (odds ratio (OR)=1.02, 95% confidence interval (CI)=0.95-1.10), serous EOC (OR=1.08, 95%CI=0.98-1.18), familial EOC (OR=1.09, 95%CI=0.78-1.54), or among women carrying deleterious mutations in BRCA1 (OR=1.09, 95%CI=0.88-1.36). There was little evidence for association with survival time among unselected cases (hazard ratio (HR)=1.10, 95%CI=0.99-1.22), among serous cases (HR=1.12, 95%CI=0.99-1.28), or with progression-free survival in 540 cases treated with carboplatin and paclitaxel (HR=1.18, 95%CI=0.93-1.52). Conclusions These data exclude the possibility of an association between rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer. Use of this SNP for ovarian cancer clinical risk prediction therefore appears unwarranted. PMID:21385923

Serum and saliva magnesium in postmenopausal women with xerostomia.

PubMed

Agha-Hosseini, F; Mirzaii-Dizgah, I

2012-10-01

The aim of this study was to investigate serum, stimulated and unstimulated salivary magnesium in postmenopausal women with xerostomia. A case-control study was carried out on 60 selected postmenopausal women aged 41-77 years with or without xerostomia (30 as cases with xerostomia and 30 as controls without xerostomia), conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. Unstimulated and paraffin-stimulated saliva samples were obtained by expectoration. Magnesium concentration was determined by the spectrophotometer method. Statistical analysis was carried out using Student's t-test. The mean serum concentration, but not stimulated and unstimulated whole saliva magnesium concentrations, was significantly higher in the cases than in the controls. Serum magnesium level appears to be associated with xerostomia in menopause.

Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study

PubMed Central

Zar, HJ; Barnett, W; Stadler, A; Gardner-Lubbe, S; Myer, L; Nicol, MP

2016-01-01

Background Pneumonia is a leading cause of mortality and morbidity in children globally. The aetiology of pneumonia following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low- and middle-income countries; furthermore most data is from cross-sectional studies of hospitalized cases. We aimed to longitudinally investigate the incidence and aetiology of childhood pneumonia in a South African birth cohort. Methods Children in the Drakenstein Child Health Study were followed from birth from May 2012 to Dec 2014. Immunizations included acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs (NPs) collected 2-weekly through infancy. Pneumonia episodes were identified and blood, NPs and induced sputum (IS) specimens obtained. Multiplex real-time PCR for pathogens was done on NPs and IS of pneumonia cases and on NPs of age- and site-matched controls. Associations between organisms and pneumonia used conditional logistic regression; results are presented as odds ratios (OR) with 95% confidence intervals (CI). Findings Overall 314 pneumonia cases occurred (incidence 0·27 episodes per child year (e/cy); median age 5 months) in 967 children during 1145 child-years of follow-up. Severe pneumonia occurred in 60 (21%) of cases (incidence 0·07 e/cy) with a case fatality ratio of 1%. A median of 5 organisms were detected in cases and controls with a median of 6 on IS (p=0·48 compared to NPs). Bordetella pertussis [OR 11·08; 95% CI 1·33-92·54; 7/696 positive], Respiratory Syncytial Virus [OR 8·05; 95% CI 4·21-15·38; 83/696 positive] or influenza virus [OR 4·13; 95% CI 2·06-8·26; 43/696 positive] were most strongly associated with pneumonia; bocavirus, parainfluenza virus, adenovirus, cytomegalovirus and Haemophilus influenzae. were also associated with pneumonia. In cases, testing of IS in addition to NPs provided incremental yield for B. pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. RSV was the most frequently detected pathogen associated with pneumonia; influenza virus and B. pertussis were also strongly associated with pneumonia. Testing of IS increases the yield for several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. PMID:27117547

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study.

PubMed

Robles, Claudia; Casabonne, Delphine; Benavente, Yolanda; Costas, Laura; Gonzalez-Barca, Eva; Aymerich, Marta; Campo, Elias; Tardon, Adonina; Jiménez-Moleón, José J; Castaño-Vinyals, Gemma; Dierssen-Sotos, Trinidad; Michel, Angelika; Kranz, Lena; Aragonés, Nuria; Pollan, Marina; Kogevinas, Manolis; Pawlita, Michael; de Sanjose, Silvia

2015-08-01

Merkel cell polyomavirus (MCPyV) has been suspected to cause chronic lymphocytic leukaemia (CLL) but previous data are inconsistent. We measured seroreactivities of nine polyomaviruses (MCPyV, BKPyV, JCPyV, LPyV, KIPyV, WUPyV, HPyV-6, HPyV-7 and TSPyV) in 359 CLL cases and 370 controls using bead-based multiplex serology technology. We additionally tested two herpesviruses (HSV-1 and CMV). Associations between disease and viral seroreactivities were assessed using logistic regression. All human viruses showed high seroprevalences (69-99%) against structural proteins in controls but significantly lower viral seroprevalences in cases (58-94%; OR range = 0.21-0.70, P value < 0.05), except for MCPyV (OR = 0.79, 95% CI = 0.54-1.16). Lower seroreactivity levels were observed among CLL subjects, with significant differences already observed at early stages of disease, unrelated to treatment status. Seroreactivities against polyomavirus related oncoproteins were almost null. Our data suggest no association for MCPyV polyomavirus with CLL development and an unlikely association for other polyomaviruses tested.

Artistic creativity and risk for schizophrenia, bipolar disorder and unipolar depression: a Swedish population-based case-control study and sib-pair analysis.

PubMed

MacCabe, J H; Sariaslan, A; Almqvist, C; Lichtenstein, P; Larsson, H; Kyaga, S

2018-06-01

Many studies have addressed the question of whether mental disorder is associated with creativity, but high-quality epidemiological evidence has been lacking.AimsTo test for an association between studying a creative subject at high school or university and later mental disorder. In a case-control study using linked population-based registries in Sweden (N = 4 454 763), we tested for associations between tertiary education in an artistic field and hospital admission with schizophrenia (N = 20 333), bipolar disorder (N = 28 293) or unipolar depression (N = 148 365). Compared with the general population, individuals with an artistic education had increased odds of developing schizophrenia (odds ratio = 1.90, 95% CI = [1.69; 2.12]) bipolar disorder (odds ratio = 1.62 [1.50; 1.75]) and unipolar depression (odds ratio = 1.39 [1.34; 1.44]. The results remained after adjustment for IQ and other potential confounders. Students of artistic subjects at university are at increased risk of developing schizophrenia, bipolar disorder and unipolar depression in adulthood.Declaration of interestNone.

The Relationship between Food Insecurity and Esophageal and Gastric Cancers: A Case-Control Study.

PubMed

Daneshi-Maskooni, Milad; Badri-Fariman, Mahtab; Habibi, Nahal; Dorosty-Motlagh, Ahmadreza; Yavari, Hashem; Kashani, Arvin; Hosseini, Mostafa

2017-06-14

Food insecurity is defined as the limited or uncertain availability of enough food for permanent active and healthy life. Upper gastrointestinal (GI) cancers (esophagus and stomach) are one of five most common cancers in Iran. This study aimed to determine the association of food insecurity and upper GI cancers in newly diagnosed patients. Case-control study. Overall, 120 patients with upper GI cancers as cases and 120 patients with orthopedic, ear-nose-throat (ENT), and neurologic diseases as controls were recruited from Imam Khomeini Hospital, Tehran, Iran in 2013. The patients were newly diagnosed using endoscopy or imaging or biopsy methods. They were individually matched for age, sex, and residential area. The general and United States Department of Agriculture (USDA) household food security questionnaires were completed. The univariate and multivariate conditional logistic regression tests were applied using the Stata 11SE statistical software. The food insecurity prevalence was 69.2% and 43.3% in cases and controls, respectively. Food insecurity, low economic level and family history of cancer were significantly associated with cancer (P<0.05). Food insecurity was one of the important risk factors for upper GI cancers that health care providers should consider it.

Factors associated with poor knowledge among adults on tuberculosis in Bangladesh: results from a nationwide survey.

PubMed

Hossain, Shahed; Zaman, Khalequ; Quaiyum, Abdul; Banu, Sayera; Husain, Ashaque; Islam, Akramul; Borgdorff, Martien; van Leth, Frank

2015-05-01

In 2012, Bangladesh continues to be one of the 22 high tuberculosis (TB) burden countries in the world. Although free diagnosis and management for TB is available throughout the country, case notification rate/100,000 population for new smear positive (NSP) cases under the national TB control programme (NTP) remained at around 70/100,000 population and have not changed much since 2006. Knowledge on TB disease, treatment and its management could be an important predictor for utilization of TB services and influence case detection under the NTP. Our objective is to describe knowledge of TB among newly diagnosed TB cases and community controls to assess factors associated with poor knowledge in order to identify programmatic implications for control measures. Embedded in TB prevalence survey 2007-2009, we included 240 TB cases from the TB registers and 240 persons ≥ 15 years of age randomly selected from the households where the survey was implemented. All participants were interviewed using a structured, pre-tested questionnaire to evaluate their TB knowledge. Regression analyses were done to assess associations with poor knowledge of TB. Our survey documented that overall there was fair knowledge in all domains investigated. However, based on the number of correct answers to the questionnaires, community controls showed significantly poorer knowledge than the TB cases in the domains of TB transmission (80% vs. 88%), mode of transmission (67% vs. 82%), knowing ≥ 1 suggestive symptoms including cough (78% vs. 89%), curability of TB (90% vs. 98%) and availability of free treatment (75% vs. 95%). Community controls were more likely to have poor knowledge of TB issues compared to the TB cases even after controlling for other factors such as education and occupation in a multivariate model (OR 3.46, 95% CI: 2.00-6.09). Knowledge on various aspects of TB and TB services varies significantly between TB cases and community controls in Bangladesh. The overall higher levels of knowledge in TB cases could identify them as peer educators in ongoing communication approaches to improve care seeking behavior of the TB suspects in the community and hence case detection.

Duration of protection of pentavalent rotavirus vaccination in Nicaragua.

PubMed

Patel, Manish; Pedreira, Cristina; De Oliveira, Lucia Helena; Umaña, Jazmina; Tate, Jacqueline; Lopman, Ben; Sanchez, Edmundo; Reyes, Martha; Mercado, Juan; Gonzalez, Alcides; Perez, Maria Celina; Balmaceda, Angel; Andrus, Jon; Parashar, Umesh

2012-08-01

To evaluate the duration of protection of pentavaent rotavirus vaccine (RV5) against rotavirus hospitalizations in Nicaragua, a developing country in Central America. We conducted a case-control study at 4 hospitals from 2007 through 2010, including 1016 children hospitalized with laboratory-confirmed rotavirus diarrhea, 4930 controls with nonrotavirus diarrhea (ie, "test-negative"), and 5627 controls without diarrhea. All cases and controls were aged ≥ 6 months and born after August 2006. Outcomes included odds of antecedent vaccination between case-patients and controls, and effectiveness of vaccination (1 - adjusted odds ratio [OR] × 100). Duration of protection was assessed by comparing effectiveness among children aged <1 year compared with ≥ 1 year. Indicators of socioeconomic conditions and nonrotavirus vaccination (oral polio vaccine and diphtheria/tetanus/pertussis/hepatitis A/hepatitis B) for test-negative controls were more comparable to the rotavirus case-patients than nondiarrhea controls. RV5 vaccination was associated with a significantly lower risk of rotavirus hospitalization by using test-negative controls (OR: 0.55; 95% confidence interval [CI]: 0.41-0.74) and nondiarrhea controls (OR: 0.30; 95% CI: 0.22-0.40). Risk of rotavirus hospitalization was twofold lower among RV5 vaccinated children aged <1 year (OR: 0.36; 95% CI: 0.22-0.57) compared with RV5 vaccinated children aged ≥ 1 year (OR: 0.70; 95% CI: 0.47-1.05). RV5 provided good protection against severe rotavirus disease in Nicaragua during the first year of life, when most severe and fatal rotavirus disease in developing countries occurs. However, the decline in protection with age warrants monitoring of disease among older children and consideration of a booster dose evaluation at the end of infancy.

Significance of neurexin and neuroligin polymorphisms in regulating risk of Hirschsprung's disease.

PubMed

Li, Yanhong; Liu, Hui; Dong, Yubin

2018-06-01

By performing a basic case-control study among a Chinese population, the aims of this study were to explore if single nucleotide polymorphisms (SNPs) within neurexin and neuroligin were associated with susceptibility to Hirschsprung's disease (HD). Eleven SNPs within neurexin and neuroligin were selected in this basic case-control study, and this study recruited 210 children with HD and 187 healthy children. The t-test and Χ 2 test were used to find the difference between case and control in their clinical variables. OR and 95% CI were used to assess the association between HD susceptibility and neurexin/neuroligin polymorphisms/haplotypes. Several SNPs were significantly associated with altered risk of HD in the Chinese Han population, including rs1421589 within NRXN1 , rs11795613 and rs4844285 within NLGN3, as well as rs5961397, rs7157669 and rs724373 within NLGX4X (all P<0.05). Further studies presented that the effects of rs1421589 within NRXN1 , rs4844285 and rs11795613 within NLGN3 , as well as rs5961397 within NLGX4X on HD phenotypes were also statistically significant (all P<0.05). Conclusively, the polymorphisms and haplotypes situated within neurexin and neuroligin were markedly associated with the onset of HD, implying that mutations of neurexin and neuroligin might serve as the treatment target for HD for the Chinese children. © American Federation for Medical Research (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Analysis of Copy Number Variants on Chromosome 21 in Down Syndrome-Associated Congenital Heart Defects.

PubMed

Rambo-Martin, Benjamin L; Mulle, Jennifer G; Cutler, David J; Bean, Lora J H; Rosser, Tracie C; Dooley, Kenneth J; Cua, Clifford; Capone, George; Maslen, Cheryl L; Reeves, Roger H; Sherman, Stephanie L; Zwick, Michael E

2018-01-04

One in five people with Down syndrome (DS) are born with an atrioventricular septal defect (AVSD), an incidence 2000 times higher than in the euploid population. The genetic loci that contribute to this risk are poorly understood. In this study, we tested two hypotheses: (1) individuals with DS carrying chromosome 21 copy number variants (CNVs) that interrupt exons may be protected from AVSD, because these CNVs return AVSD susceptibility loci back to disomy, and (2) individuals with DS carrying chromosome 21 genes spanned by microduplications are at greater risk for AVSD because these microduplications boost the dosage of AVSD susceptibility loci beyond a tolerable threshold. We tested 198 case individuals with DS+AVSD, and 211 control individuals with DS and a normal heart, using a custom microarray with dense probes tiled on chromosome 21 for array CGH (aCGH). We found that neither an individual chromosome 21 CNV nor any individual gene intersected by a CNV was associated with AVSD in DS. Burden analyses revealed that African American controls had more bases covered by rare deletions than did African American cases. Inversely, we found that Caucasian cases had more genes intersected by rare duplications than did Caucasian controls. We also showed that previously DS+AVSD (DS and a complete AVSD)-associated common CNVs on chromosome 21 failed to replicate. This research adds to the swell of evidence indicating that DS-associated AVSD is similarly heterogeneous, as is AVSD in the euploid population. Copyright © 2018 Rambo-Martin et al.

Impact of innate immunity in a subset of children with autism spectrum disorders: a case control study

PubMed Central

Jyonouchi, Harumi; Geng, Lee; Cushing-Ruby, Agnes; Quraishi, Huma

2008-01-01

Background Among patients with autism spectrum disorders (ASD) evaluated in our clinic, there appears to be a subset that can be clinically distinguished from other ASD children because of frequent infections (usually viral) accompanied by worsening behavioural symptoms and/or loss/decrease in acquired skills. This study assessed whether these clinical features of this ASD subset are associated with atopy, asthma, food allergy (FA), primary immunodeficiency (PID), or innate immune responses important in viral infections. Methods This study included the ASD children described above (ASD test, N = 26) and the following controls: ASD controls (N = 107), non-ASD controls with FA (N = 24), non-ASD controls with chronic rhinosinusitis/recurrent otitis media (CRS/ROM; N = 38), and normal controls (N = 43). We assessed prevalence of atopy, asthma, FA, CRS/ROM, and PID. Innate immune responses were assessed by measuring production of proinflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in response to agonists of Toll-like receptors (TLRs), with or without pre-treatment of lipopolysaccharide (LPS), a TLR4 agonist. Results Non-IgE mediated FA was equally prevalent in both ASD test and ASD control groups, occurring at higher frequency than in the non-ASD controls. Allergic rhinitis, atopic/non-atopic asthma, and atopic dermatitis were equally prevalent among the study groups except for the CRS/ROM group in which non-atopic asthma was more prevalent (52.6%). CRS/ROM and specific polysaccharide antibody deficiency (SPAD) were more prevalent in the ASD test group than in the ASD control, FA, and normal control groups: 23.1% vs. < 5% for CRS/ROS and 19.2% vs. < 1% for SPAD. However, CRS/ROM patients had the highest prevalence of SPAD (34.2%). When compared to ASD and normal case controls, PBMCs from 19 non-SPAD, ASD test group children produced: 1) less IL-1β with a TLR7/8 agonist, less IL-10 with a TLR2/6 agonist, and more IL-23 with a TLR4 agonist without LPS pre-treatment, and 2) less IL-1β with TLR4/7/8 agonists with LPS pre-treatment. These are cytokines associated with the neuro-immune network. Conclusion Clinical features of the ASD test group were not associated with atopy, asthma, FA, or PID in our study but may be associated with altered TLR responses mediating neuro-immune interactions. PMID:19025588

An analysis of gene expression in PTSD implicates genes involved in the glucocorticoid receptor pathway and neural responses to stress

PubMed Central

Logue, Mark W.; Smith, Alicia K.; Baldwin, Clinton; Wolf, Erika J.; Guffanti, Guia; Ratanatharathorn, Andrew; Stone, Annjanette; Schichman, Steven A.; Humphries, Donald; Binder, Elisabeth B.; Arloth, Janine; Menke, Andreas; Uddin, Monica; Wildman, Derek; Galea, Sandro; Aiello, Allison E.; Koenen, Karestan C.; Miller, Mark W.

2015-01-01

We examined the association between posttraumatic stress disorder (PTSD) and gene expression using whole blood samples from a cohort of trauma-exposed white non-Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and gene transcripts were analyzed. We found 41 that were differentially expressed in PTSD cases versus controls (multiple-testing corrected p<0.05). The most significant was DSCAM, a neurological gene expressed widely in the developing brain and in the amygdala and hippocampus of the adult brain. We then examined the 41 differentially expressed genes in a meta-analysis using two replication cohorts and found significant associations with PTSD for 7 of the 41 (p<0.05), one of which (ATP6AP1L) survived multiple-testing correction. There was also broad evidence of overlap across the discovery and replication samples for the entire set of genes implicated in the discovery data based on the direction of effect and an enrichment of p<0.05 significant probes beyond what would be expected under the null. Finally, we found that the set of differentially expressed genes from the discovery sample was enriched for genes responsive to glucocorticoid signaling with most showing reduced expression in PTSD cases compared to controls. PMID:25867994

No association between catechol-O-methyltransferase polymorphisms and neurotic disorders among mainland Chinese university students.

PubMed

Kou, Changgui; Meng, Xiangfei; Xie, Bing; Shi, Jieping; Yu, Qiong; Yu, Yaqin; D'Arcy, Carl

2012-07-30

This study investigates the genetic association between catechol-O-methyltransferase (COMT) gene polymorphisms and neurotic disorders. Data were derived from a case-control association study of 255 undergraduates affected by neurotic disorders and 269 matched healthy undergraduate controls. The polymorphisms of eight tag single nucleotide polymorphisms (SNPs) on the COMT gene were tested using polymerase chain reaction (PCR)-based Ligase Detection Reaction (PCR-LDR). The eight tag SNPs on the COMT gene assessed were not associated with neurotic disorders. Our finding suggests that the COMT gene may not be a susceptibility gene for neurotic disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association of multiple genetic variants with chronic obstructive pulmonary disease susceptibility in Hainan region.

PubMed

Ding, Yipeng; Niu, Huan; Zhou, Long; Zhou, Wenjing; Chen, Jiannan; Xie, Shiliang; Geng, Tingting; Ouyang, Yanhong; He, Ping; Sun, Pei; Feng, Tian; Jin, Tianbo

2017-11-01

Recent genome-wide association studies have shown associations between variants in loci (4q28.1, 6p21.32, 6p21.1, 6q16.1, 10q22.1 and 10q22.3) and chronic obstructive pulmonary disease (COPD) or smoking behaviors. The objective of this study was to look for associations between 16 single nucleotide polymorphisms (SNP) at these six loci and COPD susceptibility in Hainan region. A case-control cohort was composed of 200 COPD cases and 401 controls that were genotyped and analyzed statistically. Odds ratios (OR) and 95% confidence intervals (CIs) were computed by chi-square (χ 2 ) test and genetic models by unconditional logistic regression. After Hardy-Weinberg equilibrium (HWE) P value screening, we excluded the SNP rs12220777 with P < 0.001. By χ 2 test only rs9296092 which located on 6p21.32 was provided the strongest evidence of an increasing risk of COPD with an OR of 3.28 (95% CI = 1.03 - 2.32; P = 0.003) between cases and controls. By genetic models analysis, we not only found rs9296092 increased COPD risk, but also found in the over-dominant model the genotype 'C/T' (OR = 0.55; 95% CI = 0.33 - 0.93; P = 0.023) of rs950063 was proved to be associated with decreased COPD risk. This study is the first to provide evidence of importance of rs9296092 and rs950063 for risk of COPD in Hainan Province. Further studies are needed to characterize the functional sequences that cause COPD. © 2015 John Wiley & Sons Ltd.

Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study

PubMed Central

Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

2016-01-01

Background Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM) risk. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results Two case-control studies (846 MM patients and 843 controls) and five cohort studies (including 844,246 participants and 5,737 MM cases) were identified. For caffeinated coffee, the pooled relative risk (RR) of MM was 0.81 [95% confidential interval (95% CI) = 0.68–0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912–0.999) for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326). Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81–1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake). Conclusions This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings. PMID:26816289

A case-control study on risk factors of breast cancer in Han Chinese women.

PubMed

Liu, Li-Yuan; Wang, Fei; Cui, Shu-De; Tian, Fu-Guo; Fan, Zhi-Min; Geng, Cui-Zhi; Cao, Xu-Chen; Yang, Zhen-Lin; Wang, Xiang; Liang, Hong; Wang, Shu; Jiang, Hong-Chuan; Duan, Xue-Ning; Wang, Hai-Bo; Li, Guo-Lou; Wang, Qi-Tang; Zhang, Jian-Guo; Jin, Feng; Tang, Jin-Hai; Li, Liang; Zhu, Shi-Guang; Zuo, Wen-Shu; Yu, Li-Xiang; Xiang, Yu-Juan; Zhou, Fei; Li, Liang; Zhang, Qiang; Fu, Qin-Ye; Ma, Zhong-Bing; Gao, De-Zong; Li, Yu-Yang; Liu, Lu; Ye, Chun-Miao; Wang, Yong-Jiu; Zhou, Wen-Zhong; Yu, Zhi-Gang

2017-11-14

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P < 0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Escherichia coli O157:H7 outbreak linked to salami, British Columbia, Canada, 1999.

PubMed Central

MacDonald, D. M.; Fyfe, M.; Paccagnella, A.; Trinidad, A.; Louie, K.; Patrick, D.

2004-01-01

An outbreak of E. coli O157:H7 infections was identified in November 1999 with a fivefold increase in the occurrence of laboratory-confirmed cases of E. coli O157:H7 infection. A matched case-control study was conducted. Samples of food from cases and from retailers were analysed for the presence of E. coli O157:H7. A total of 143 cases were identified over a 12-week period with the same pulsed-field gel electrophoresis (PFGE) pattern. The case-control study found that Company A salami was significantly associated with illness (Mantel-Haenszel matched odds ratio 10.0%, 95% CI 1.4-434, P=0.01). Company A salami tested positive for E. coli O157:H7 and isolates had the same PFGE pattern as case isolates. An immediate voluntary national recall of Company A dry fermented meat products took place. Findings from the investigation of this outbreak suggest that the hold-and-test option may not be adequate to prevent shiga-toxigenic Escherichia coli (STEC) infection in salami consumers. PMID:15061503

Test Cases for the Benchmark Active Controls: Spoiler and Control Surface Oscillations and Flutter

NASA Technical Reports Server (NTRS)

Bennett, Robert M.; Scott, Robert C.; Wieseman, Carol D.

2000-01-01

As a portion of the Benchmark Models Program at NASA Langley, a simple generic model was developed for active controls research and was called BACT for Benchmark Active Controls Technology model. This model was based on the previously-tested Benchmark Models rectangular wing with the NACA 0012 airfoil section that was mounted on the Pitch and Plunge Apparatus (PAPA) for flutter testing. The BACT model had an upper surface spoiler, a lower surface spoiler, and a trailing edge control surface for use in flutter suppression and dynamic response excitation. Previous experience with flutter suppression indicated a need for measured control surface aerodynamics for accurate control law design. Three different types of flutter instability boundaries had also been determined for the NACA 0012/PAPA model, a classical flutter boundary, a transonic stall flutter boundary at angle of attack, and a plunge instability near M = 0.9. Therefore an extensive set of steady and control surface oscillation data was generated spanning the range of the three types of instabilities. This information was subsequently used to design control laws to suppress each flutter instability. There have been three tests of the BACT model. The objective of the first test, TDT Test 485, was to generate a data set of steady and unsteady control surface effectiveness data, and to determine the open loop dynamic characteristics of the control systems including the actuators. Unsteady pressures, loads, and transfer functions were measured. The other two tests, TDT Test 502 and TDT Test 5 18, were primarily oriented towards active controls research, but some data supplementary to the first test were obtained. Dynamic response of the flexible system to control surface excitation and open loop flutter characteristics were determined during Test 502. Loads were not measured during the last two tests. During these tests, a database of over 3000 data sets was obtained. A reasonably extensive subset of the data sets from the first two tests have been chosen for Test Cases for computational comparisons concentrating on static conditions and cases with harmonically oscillating control surfaces. Several flutter Test Cases from both tests have also been included. Some aerodynamic comparisons with the BACT data have been made using computational fluid dynamics codes at the Navier-Stokes level (and in the accompanying chapter SC). Some mechanical and active control studies have been presented. In this report several Test Cases are selected to illustrate trends for a variety of different conditions with emphasis on transonic flow effects. Cases for static angles of attack, static trailing-edge and upper-surface spoiler deflections are included for a range of conditions near those for the oscillation cases. Cases for trailing-edge control and upper-surface spoiler oscillations for a range of Mach numbers, angle of attack, and static control deflections are included. Cases for all three types of flutter instability are selected. In addition some cases are included for dynamic response measurements during forced oscillations of the controls on the flexible mount. An overview of the model and tests is given, and the standard formulary for these data is listed. Some sample data and sample results of calculations are presented. Only the static pressures and the first harmonic real and imaginary parts of the pressures are included in the data for the Test Cases, but digitized time histories have been archived. The data for the Test Cases are also available as separate electronic files.

Glutathione S-transferase M1 (GSTM1) polymorphisms and lung cancer: a literature-based systematic HuGE review and meta-analysis.

PubMed

Carlsten, C; Sagoo, G S; Frodsham, A J; Burke, W; Higgins, J P T

2008-04-01

Multiple genes have been studied for potential associations with lung cancer. The gene most frequently associated with increased risk has been glutathione S-transferase M1 (GSTM1). The glutathione S-transferase enzyme family is known to catalyze detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. In this review, the authors summarize the available evidence associating lung cancer with the GSTM1 gene. They describe results from an updated meta-analysis of 98 published genetic association studies investigating the relation between the GSTM1 null variant and lung cancer risk including 19,638 lung cancer cases and 25,266 controls (counting cases and controls in each study only once). All studies considered, the GSTM1 null variant was associated with an increased risk of lung cancer (odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.14, 1.30), but no increase in risk was seen (OR = 1.01, 95% CI: 0.91, 1.12) when only the five largest studies (>500 cases each) were considered. Furthermore, while GSTM1 null status conferred a significantly increased risk of lung cancer to East Asians (OR = 1.38, 95% CI: 1.24, 1.55), such a genotype did not confer increased risk to Caucasians. More data regarding the predictive value of GSTM1 genetic testing are needed before population-based testing may be reasonably considered.

Is there an association between bruxism and intestinal parasitic infestation in children?

PubMed

Díaz-Serrano, Kranya Victoria; da Silva, Carolina Brunelli Alvares; de Albuquerque, Sérgio; Pereira Saraiva, Maria da Conceição; Nelson-Filho, Paulo

2008-01-01

Multiple factors have been considered in the etiology of bruxism in pediatric patients, among which are infestations by intestinal parasites suggested by some authors. No empirical evidence exists, however, of such association. Therefore, this study's purpose was to investigate the existence of an association between bruxism and intestinal parasitic infestation in children. Fifty-seven 6- to 11-year-olds (30 cases and 27 controls) who had not used anthelminthics 2 months before the baseline examination were enrolled in the study. A diagnosis of bruxism was based on an intraoral clinical examination performed by a single trained examiner and on the parent/guardian's report of any perceived parafunctional habits (questionnaire-based interview). Bruxism cases were defined as those children with a report of currently perceived habits of eccentric or centric bruxism (tooth-grinding and tooth-clenching, respectively) combined with clinical evidence of nonphysiologic wear facets. The volunteers were required to collect 3 fecal samples (1 every 2 to 3 days). Parasitologic analysis was performed using the spontaneous sedimentation method. Data gathered from the intraoral clinical examination, questionnaire, and parasitologic analysis were tabulated and submitted to statistical analysis using the chi-square test and student's t test. Intestinal parasitic infestation was observed in 30% (N=9) of cases and 41% (N=11) of controls, but no statistically significant association was observed (P=.40). This study's findings do not support the existence of an association between intestinal parasitic infestation and bruxism among the evaluated pediatric population.

Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.

PubMed

Janse, Marcel; Lamberts, Laetitia E; Franke, Lude; Raychaudhuri, Soumya; Ellinghaus, Eva; Muri Boberg, Kirsten; Melum, Espen; Folseraas, Trine; Schrumpf, Erik; Bergquist, Annika; Björnsson, Einar; Fu, Jingyuan; Jan Westra, Harm; Groen, Harry J M; Fehrmann, Rudolf S N; Smolonska, Joanna; van den Berg, Leonard H; Ophoff, Roel A; Porte, Robert J; Weismüller, Tobias J; Wedemeyer, Jochen; Schramm, Christoph; Sterneck, Martina; Günther, Rainer; Braun, Felix; Vermeire, Severine; Henckaerts, Liesbet; Wijmenga, Cisca; Ponsioen, Cyriel Y; Schreiber, Stefan; Karlsen, Tom H; Franke, Andre; Weersma, Rinse K

2011-06-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors. Copyright © 2011 American Association for the Study of Liver Diseases.

A Comprehensive Analysis of Common Genetic Variation Around Six Candidate Loci for Intrahepatic Cholestasis of Pregnancy

PubMed Central

Dixon, Peter H; Wadsworth, Christopher A; Chambers, Jennifer; Donnelly, Jennifer; Cooley, Sharon; Buckley, Rebecca; Mannino, Ramona; Jarvis, Sheba; Syngelaki, Argyro; Geenes, Victoria; Paul, Priyadarshini; Sothinathan, Meera; Kubitz, Ralf; Lammert, Frank; Tribe, Rachel M; Ch'ng, Chin Lye; Marschall, Hanns-Ulrich; Glantz, Anna; Khan, Shahid A; Nicolaides, Kypros; Whittaker, John; Geary, Michael; Williamson, Catherine

2014-01-01

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component. Heterozygous mutations of canalicular transporters occur in a subset of ICP cases and a population susceptibility allele (p.444A) has been identified in ABCB11. We sought to expand our knowledge of the detailed genetic contribution to ICP by investigation of common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19). METHODS: ICP patients (n=563) of white western European origin and controls (n=642) were analyzed in a case–control design. Single-nucleotide polymorphism (SNP) markers (n=83) were selected from the HapMap data set (Tagger, Haploview 4.1 (build 22)). Genotyping was performed by allelic discrimination assay on a robotic platform. Following quality control, SNP data were analyzed by Armitage's trend test. RESULTS: Cochran–Armitage trend testing identified six SNPs in ABCB11 together with six SNPs in ABCB4 that showed significant evidence of association. The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10−4 (rs3815676) and for ABCB4 it was 4.6×10−7(rs2109505). Conditional analysis of the two clusters of association signals suggested a single signal in ABCB4 but evidence for two independent signals in ABCB11. To confirm these findings, a second study was performed in a further 227 cases, which confirmed and strengthened the original findings. CONCLUSIONS: Our analysis of a large cohort of ICP cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of ICP susceptibility. PMID:24366234

Association Study between Ghrelin Gene Polymorphism and Metabolic Syndrome in a Han Chinese Population.

PubMed

You, Yueyue; Yu, Yaqin; Wu, Yanhua; Rao, Wenwang; Zhang, Yangyu; Liu, Yingyu; Yang, Guang; Fu, Yingli; Shi, Jieping; Kou, Changgui

2017-01-01

Ghrelin, in humans, is a hormone secreted from the stomach with an orexigenic effect, which is good for digestion and absorption, as well as regulating physical growth, metabolism, and energy balance. It is also involved in the development of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). This study assessed the association between single nucleotide variants of the GHRL gene and the risk of metabolic syndrome in a Han Chinese population. A case-control study was performed on 3780 Han Chinese comprising 1813 MetS cases and 1967 controls. Three missense polymorphisms in GHRL (rs26802, rs10490816, and rs696217) were selected, and the association between these polymorphisms and the risk of MetS was investigated. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF). Using Pearson's 2 test, we found that there were no significant differences in genotype distributions and allele frequencies between cases and controls (all p > 0.05). There were also no significant differences in haplotype distributions between MetS cases and healthy controls. Furthermore, we confirmed that rs26802 of the GHRL gene is associated with body mass index (BMI), waist circumference, systolic blood pressure (SBP), and fasting glucose; rs10490816 is associated with triglycerides (TG) and total cholesterol (TC); while rs696217 is associated with hip circumference and fasting glucose. We concluded that mutations in the GHRL gene did not confer risk for MetS in our study population. Therefore, functional analysis and replication studies in other populations are needed to further investigate the exact role of the GHRL gene in MetS.

Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

PubMed Central

Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

2012-01-01

Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

Autism in children and correlates in Lebanon: a pilot case-control study.

PubMed

Hamadé, Aline; Salameh, Pascale; Medlej-Hashim, Myrna; Hajj-Moussa, Elie; Saadallah-Zeidan, Nina; Rizk, Francine

2013-09-17

Autism spectrum disorder (ASD) is a neurological disorder typically appearing before the age of three. The exact cause of autism remains uncertain, and several factors may be involved in its onset: genetic factors and possible environmental factors. The aim of this study was to assess the correlates of autism in the Lebanese population. We investigated the association of autism with several factors in 86 autism cases from specialized schools for children with developmental disabilities and 172 control children from regular public schools in the same regions. Several risk factors for autism were investigated after comparison with a cohort control on parental age, sex, maternal unhappy feeling during pregnancy, consanguineous marriage, and province of residence. The Chi-square test was used to compare nominal variables, and Fisher exact test was used in case expected values within cells were inferior to five. For quantitative variables, we used t-test to compare means between two groups, after checking their distribution normality. For multivariate analysis, we used a forward stepwise likelihood ratio logistic regression. We observed male predominance (79.1%) among autistic infants. There was a significant association between autism and older parents age (OR=1.27), male sex (OR=3.38), unhappy maternal feeling during pregnancy (OR=5.77), living close to industry (OR=6.58), previous childhood infection (OR=8.85), but none concerning maternal age, paternal age and consanguinity. In this pilot epidemiological study of autism in Lebanon, we found several prenatal and perinatal risk factors for autism that could be modified.

Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

PubMed

Pierce Campbell, Christine M; Gheit, Tarik; Tommasino, Massimo; Lin, Hui-Yi; Torres, B Nelson; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Sirak, Bradley A; Abrahamsen, Martha; Carvalho da Silva, Roberto J; Sichero, Laura; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-10-01

Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. Copyright © 2016. Published by Elsevier Inc.

Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

PubMed

Oh, Sung-Hee; Kang, Hye-Young

2018-01-01

We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Genetic risk factors for ovarian cancer and their role for endometriosis risk.

PubMed

Burghaus, Stefanie; Fasching, Peter A; Häberle, Lothar; Rübner, Matthias; Büchner, Kathrin; Blum, Simon; Engel, Anne; Ekici, Arif B; Hartmann, Arndt; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P

2017-04-01

Several genetic variants have been validated as risk factors for ovarian cancer. Endometriosis has also been described as a risk factor for ovarian cancer. Identifying genetic risk factors that are common to the two diseases might help improve our understanding of the molecular pathogenesis potentially linking the two conditions. In a hospital-based case-control analysis, 12 single nucleotide polymorphisms (SNPs), validated by the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncological Gene-environment Study (COGS) project, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 385 cases and 484 controls were analyzed. Odds ratios and P values were obtained using simple logistic regression models, as well as from multiple logistic regression models with adjustment for clinical predictors. rs11651755 in HNF1B was found to be associated with endometriosis in this case-control study. The OR was 0.66 (95% CI, 0.51 to 0.84) and the P value after correction for multiple testing was 0.01. None of the other genotypes was associated with a risk for endometriosis. As rs11651755 in HNF1B modified both the ovarian cancer risk and also the risk for endometriosis, HNF1B may be causally involved in the pathogenetic pathway leading from endometriosis to ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Polymorphisms in xenobiotic metabolizing enzymes and diet influence colorectal adenoma risk.

PubMed

Northwood, Emma L; Elliott, Faye; Forman, David; Barrett, Jennifer H; Wilkie, Murray J V; Carey, Francis A; Steele, Robert J C; Wolf, Roland; Bishop, Timothy; Smith, Gillian

2010-05-01

We have earlier shown that diet and xenobiotic metabolizing enzyme genotypes influence colorectal cancer risk, and now investigate whether similar associations are seen in patients with premalignant colorectal adenomas (CRA), recruited during the pilot phase of the Scottish Bowel Screening Programme. Nineteen polymorphisms in 13 genes [cytochrome P450 (P450), glutathione S-transferase (GST), N-acetyl transferase, quinone reductase (NQ01) and microsomal epoxide hydrolase (EPHX1) genes] were genotyped using multiplex PCR or Taqman-based allelic discrimination assays and analyzed in conjunction with diet, assessed by food frequency questionnaire, in a case-control study [317 CRA cases (308 cases genotyped), 296 controls]. Findings significant at a nominal 5% level are reported. CRA risk was inversely associated with fruit (P=0.02, test for trend) and vegetable (P=0.001, test for trend) consumption. P450 CYP2C9*3 heterozygotes had reduced CRA risk compared with homozygotes for the reference allele [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.36-0.99], whereas CYP2D6*4 homozygotes (OR: 2.72; 95% CI: 1.18-6.27) and GSTM1 'null' individuals (OR: 1.43; 95% CI: 1.04-1.98) were at increased risk. The protective effect of fruit consumption was confined to GSTP1 (Ala114Val) reference allele homozygotes (OR: 0.49; 95% CI: 0.34-0.71, P=0.03 for interaction). CRA risk was not associated with meat consumption, although a significant interaction between red meat consumption and EPHX1 (His139Arg) genotype was noted (P=0.02 for interaction). We report the novel associations between P450 genotype and CRA risk, and highlight the risk association with GSTM1 genotype, common to our CRA and cancer case-control series. In addition, we report a novel modifying influence of GSTP1 genotype on dietary chemoprevention. These novel findings require independent confirmation.

Air pollution and childhood leukaemia: a nationwide case-control study in Italy.

PubMed

Badaloni, C; Ranucci, A; Cesaroni, G; Zanini, G; Vienneau, D; Al-Aidrous, F; De Hoogh, K; Magnani, C; Forastiere, F

2013-12-01

Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

Is bisphosphonate therapy for benign bone disease associated with impaired dental healing? A case-controlled study

PubMed Central

2011-01-01

Background Bisphosphonates are common first line medications used for the management of benign bone disease. One of the most devastating complications associated with bisphosphonate use is osteonecrosis of the jaws which may be related to duration of exposure and hence cumulative dose, dental interventions, medical co-morbidities or in some circumstances with no identifiable aggravating factor. While jaw osteonecrosis is a devastating outcome which is currently difficult to manage, various forms of delayed dental healing may be a less dramatic and, therefore, poorly-recognised complications of bisphosphonate use for the treatment of osteoporosis. It is hypothesised that long-term (more than 1 year's duration) bisphosphonate use for the treatment of post-menopausal osteoporosis or other benign bone disease is associated with impaired dental healing. Methods/Design A case-control study has been chosen to test the hypothesis as the outcome event rate is likely to be very low. A total of 54 cases will be recruited into the study following review of all dental files from oral and maxillofacial surgeons and special needs dentists in Victoria where potential cases of delayed dental healing will be identified. Potential cases will be presented to an independent case adjudication panel to determine if they are definitive delayed dental healing cases. Two hundred and fifteen controls (1:4 cases:controls), matched for age and visit window period, will be selected from those who have attended local community based referring dental practices. The primary outcome will be the incidence of delayed dental healing that occurs either spontaneously or following dental treatment such as extractions, implant placement, or denture use. Discussion This study is the largest case-controlled study assessing the link between bisphosphonate use and delayed dental healing in Australia. It will provide invaluable data on the potential link between bisphosphonate use and osteonecrosis of the jaws. PMID:21477374

TNF-α-308/-238 polymorphisms are associated with gastric cancer: A case-control family study in China.

PubMed

Xu, Yajuan; Cao, Xiaoqin; Jiang, Jicheng; Chen, Yi; Wang, Kaijuan

2017-02-01

Associations of TNF-α-308 (rs1800629) and -238 (rs361525) with gastric cancer had the inconsistent indication among different populations. In this case-control family study, 47 families were determined with the probands diagnosed with gastric cancer (case family, n=296), accordingly 47 families without gastric cancer were matched with the case families by multivariate distribution of age, sex, social class, and pedigree size (control family, n=319). Polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) was used to identify the TNF genotype. Chi-square test was used to compare the groups regarding genotype and the allele frequencies, HWE test for Hardy-Weinberg equilibrium. The frequencies of TNF-α-308 GA and AA genotypes were significantly higher in case family than that in control family. The risk of gastric cancer was increased in GA and AA carriers in the first degree (OR=2.06, 95% CI=1.20-3.51 and OR=4.89, 95% CI=2.74-8.74), however the similar result was not found in the second degree. Helicobacter pylori infection status were significantly associated with risk of gastric cancer in first-degree relatives (OR=1.96, 95% CI=1.26-3.05) while no statistical significance was noted in the second-degree relatives. Haplotypes of TNF-α-308/-238 alleles, GA/GG, AA/GG and AA/GA indicated the susceptibilities to gastric cancer with OR and 95% confident intervals resulting 2.07 (1.34-3.21), 4.49 (2.74-7.33) and 4.98 (1.76-14.01) respectively. TNF-α-G308A (rs1800629) polymorphisms are associated with gastric cancer in Chinese population. Haplotypes of TNF-α-308/-238 GA/GG, AA/GG and AA/GA increase the susceptibilities to gastric cancer. The first-degree relatives are more likely to develop into gastric cancer with TNF-α-G308 polymorphisms and H. pylori positive than the second-degree are. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression.

PubMed

Quteineh, Lina; Preisig, Martin; Rivera, Margarita; Milaneschi, Yuri; Castelao, Enrique; Gholam-Rezaee, Mehdi; Vandenberghe, Frederik; Saigi-Morgui, Nuria; Delacrétaz, Aurélie; Cardinaux, Jean-René; Willemsen, Gonneke; Boomsma, Dorret I; Penninx, Brenda W J H; Ching-López, Ana; Conus, Philippe; Eap, Chin B

2016-07-01

Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

PubMed

Abdullah, N; Abdul Murad, N A; Attia, J; Oldmeadow, C; Mohd Haniff, E A; Syafruddin, S E; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

2015-10-01

To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Occupational asthma in an electronics factory: a case control study to evaluate aetiological factors

PubMed Central

Burge, P Sherwood; Perks, W H; O'Brien, I M; Burge, A; Hawkins, R; Brown, D; Green, M

1979-01-01

This is the final part of a study carried out to investigate occupational asthma due to sensitivity to colophony fumes (a component of soldering flux) in an electronics factory. Fifty-eight workers with occupational asthma employed on the main shop floor were investigated. In them the interval between first exposure and sensitisation varied widely with a group becoming sensitive within one to two years of first exposure, and another group whose sensitisation was delayed for three to 23 years. Once sensitised the interval between arriving at work and the onset of daily symptoms seemed to be bimodally distributed, resembling the immediate and late asthmatic symptoms seen on provocation testing. Twenty-three out of 58 had no definite daily deterioration at work but improved at the weekends. Wheeze and breathlessness occurred in the evenings at home in most, and one-third were woken by breathlessness at least on some nights. These 58 cases were compared with 48 controls without occupational asthma who had worked on the same shop floor for at least four years. Mean levels of FEV1 were significantly worse in the cases before exposure on Monday morning. The cases also had more than twice as much sickness absence as controls. FEV1 fell by more than 10% over a working shift in 33% of cases and 5% of controls. Atopy (a positive skin prick test to one or more common allergens) and a past history of allergic disease were weakly but significantly associated with being a case. The effects of smoking and a family history of allergic disease were trivial. Prick testing with an antigen derived from the colophony in the solder flux was completely negative, but cases and controls had significantly raised levels of total IgM compared with blood bank controls, perhaps suggesting some previously unrecognised immunological process. PMID:483204

A case-control study of factors associated with HIV infection among black women.

PubMed

Forna, Fatu M; Fitzpatrick, Lisa; Adimora, Adaora A; McLellan-Lemal, Eleanor; Leone, Peter; Brooks, John T; Marks, Gary; Greenberg, Alan

2006-11-01

To identify social, behavioral and epidemiologic factors associated with HIV infection among HIV-infected and HIV-uninfected black women residing in North Carolina. A case-control study conducted in August 2004 in North Carolina. Cases were 18-40-year-old women with HIV infections diagnosed from 2003-2004. Controls were 18-40-yearold, HIV-negative heterosexually active women recruited from HIV testing sites. Five focus group discussions were also conducted with women not participating in the case-control study. Multivariate analyses of 31 cases and 101 controls showed that HIV-positive women were more likely to receive public assistance [adjusted odds ratio (aOR) 7.3; 95% confidence interval (CI) 2.1, 26.0], to report a history of genital herpes infection (aOR 10.6; 95% CI 2.4, 47.2), and were less likely to have discussed a variety of sexual and behavioral issues relevant to risk of HIV infection with their male partners (aOR 0.6; 95% CI 0.4, 0.8). Focus group participants indicated that financial and social demands created competing challenges for making HIV prevention a priority. Inadequate communication between black women and their sexual partners may create barriers to sexual and behavioral risk reduction. A multidimensional approach that addresses both biological factors such as herpes infection and socioeconomic factors may be needed to reduce HIV transmission in this population.

Disease-Concordant Twins Empower Genetic Association Studies.

PubMed

Tan, Qihua; Li, Weilong; Vandin, Fabio

2017-01-01

Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost. © 2016 John Wiley & Sons Ltd/University College London.

Lessons for Control of Heroin-Associated Anthrax in Europe from 2009–2010 Outbreak Case Studies, London, UK

PubMed Central

Abbara, Aula; Brooks, Tim; Taylor, Graham P.; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel

2014-01-01

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009–2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012–13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community. PMID:24959910

Lessons for control of heroin-associated anthrax in Europe from 2009-2010 outbreak case studies, London, UK.

PubMed

Abbara, Aula; Brooks, Tim; Taylor, Graham P; Nolan, Marianne; Donaldson, Hugo; Manikon, Maribel; Holmes, Alison

2014-07-01

Outbreaks of serious infections associated with heroin use in persons who inject drugs (PWIDs) occur intermittently and require vigilance and rapid reporting of individual cases. Here, we give a firsthand account of the cases in London during an outbreak of heroin-associated anthrax during 2009-2010 in the United Kingdom. This new manifestation of anthrax has resulted in a clinical manifestation distinct from already recognized forms. During 2012-13, additional cases of heroin-associated anthrax among PWIDs in England and other European countries were reported, suggesting that anthrax-contaminated heroin remains in circulation. Antibacterial drugs used for serious soft tissue infection are effective against anthrax, which may lead to substantial underrecognition of this novel illness. The outbreak in London provides a strong case for ongoing vigilance and the use of serologic testing in diagnosis and serologic surveillance schemes to determine and monitor the prevalence of anthrax exposure in the PWID community.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

PubMed

Power, Robert A; Tansey, Katherine E; Buttenschøn, Henriette Nørmølle; Cohen-Woods, Sarah; Bigdeli, Tim; Hall, Lynsey S; Kutalik, Zoltán; Lee, S Hong; Ripke, Stephan; Steinberg, Stacy; Teumer, Alexander; Viktorin, Alexander; Wray, Naomi R; Arolt, Volker; Baune, Bernard T; Boomsma, Dorret I; Børglum, Anders D; Byrne, Enda M; Castelao, Enrique; Craddock, Nick; Craig, Ian W; Dannlowski, Udo; Deary, Ian J; Degenhardt, Franziska; Forstner, Andreas J; Gordon, Scott D; Grabe, Hans J; Grove, Jakob; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hocking, Lynne J; Homuth, Georg; Hottenga, Jouke J; Kloiber, Stefan; Krogh, Jesper; Landén, Mikael; Lang, Maren; Levinson, Douglas F; Lichtenstein, Paul; Lucae, Susanne; MacIntyre, Donald J; Madden, Pamela; Magnusson, Patrik K E; Martin, Nicholas G; McIntosh, Andrew M; Middeldorp, Christel M; Milaneschi, Yuri; Montgomery, Grant W; Mors, Ole; Müller-Myhsok, Bertram; Nyholt, Dale R; Oskarsson, Hogni; Owen, Michael J; Padmanabhan, Sandosh; Penninx, Brenda W J H; Pergadia, Michele L; Porteous, David J; Potash, James B; Preisig, Martin; Rivera, Margarita; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Smit, Johannes H; Smith, Blair H; Stefansson, Hreinn; Stefansson, Kari; Strohmaier, Jana; Sullivan, Patrick F; Thomson, Pippa; Thorgeirsson, Thorgeir E; Van der Auwera, Sandra; Weissman, Myrna M; Breen, Gerome; Lewis, Cathryn M

2017-02-15

Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10 -11 ). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Solvent oriented hobbies and the risk of systemic sclerosis.

PubMed

Nietert, P J; Sutherland, S E; Silver, R M; Pandey, J P; Dosemeci, M

1999-11-01

To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody. Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70. Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

Constructive thinking, rational intelligence and irritable bowel syndrome.

PubMed

Rey, Enrique; Moreno Ortega, Marta; Garcia Alonso, Monica-Olga; Diaz-Rubio, Manuel

2009-07-07

To evaluate rational and experiential intelligence in irritable bowel syndrome (IBS) sufferers. We recruited 100 subjects with IBS as per Rome II criteria (50 consulters and 50 non-consulters) and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire (including symptom characteristics and medical consultation) and the following tests: rational-intelligence (Wechsler Adult Intelligence Scale, 3rd edition); experiential-intelligence (Constructive Thinking Inventory); personality (NEO personality inventory); psychopathology (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social readjustment rating scale). Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. No differences were found between IBS cases and controls in terms of IQ (102.0 +/- 10.8 vs 102.8 +/- 12.6), but IBS sufferers scored significantly lower in global constructive thinking (43.7 +/- 9.4 vs 49.6 +/- 9.7). In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 (0.87-0.97)], without significant OR for total IQ. IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS.

Identification and management of filament-wound case stiffness parameters

NASA Technical Reports Server (NTRS)

Verderaime, V.; Rheinfurth, M.

1983-01-01

The high specific strength and the high specific modules made graphite epoxy laminate an expedient material substitute for the Shuttle Solid Rocket Motor steel case to substantially increase the payload performance without increasing the composite case axial growth during thrust build up which was constrained to minimize liftoff excitation effects on existing structural elements and interfaces. Parameters associated with axial growth were identified for quality and manufacturing controls. Included is an innovative method for experimentally verifying extensional elastic properties on a laminate pressurized test bottle.

H. pylori seroprevalence and risk of diabetes: An ancillary case-control study nested in the diabetes prevention program.

PubMed

Alzahrani, Saud; Nelson, Jason; Moss, Steven F; Paulus, Jessica K; Knowler, William C; Pittas, Anastassios G

2017-10-01

To determine the association between H. pylori infection and risk of incident diabetes in adults at high risk for diabetes who participated in the Diabetes Prevention Program (DPP) study. In a nested case-control study conducted among 421 adults with newly diagnosed diabetes and 421 matched controls, we examined the association between serological status of H. pylori at baseline and risk of incident diabetes over a mean follow-up period of 2.6years. Using data from the baseline visit of the DPP, we also examined the cross-sectional association between presence of H. pylori antibodies and insulin sensitivity, insulin secretion and the disposition index-like measure after a 75-g oral glucose tolerance test (OGTT). At baseline, H. pylori antibodies were present in 40% of participants who developed diabetes and 39% of controls. After adjusting for matching factors, there was no association between exposure to H. pylori and incident diabetes (odds ratio [OR] of 1.04 (95% CI, 0.77 to 1.40). In cross-sectional analyses, H. pylori status was not significantly associated with insulin sensitivity and disposition index-like measure from OGTT. In adults at high risk for diabetes, H. pylori seropositivity was not associated with risk of developing diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors Affecting Herd Status for Bovine Tuberculosis in Dairy Cattle in Northern Thailand

PubMed Central

Singhla, Tawatchai; Punyapornwithaya, Veerasak; VanderWaal, Kimberly L.; Alvarez, Julio; Sreevatsan, Srinand; Phornwisetsirikun, Somphorn; Sankwan, Jamnong; Srijun, Mongkol; Wells, Scott J.

2017-01-01

The objective of this case-control study was to identify farm-level risk factors associated with bovine tuberculosis (bTB) in dairy cows in northern Thailand. Spatial analysis was performed to identify geographical clustering of case-farms located in Chiang Mai and Chiang Rai provinces in northern Thailand. To identify management factors affecting bTB status, a matched case-control study was conducted with 20 case-farms and 38 control-farms. Case-farms were dairy farms with at least single intradermal tuberculin test- (SIT-) reactor(s) in the farms during 2011 to 2015. Control-farms were dairy farms with no SIT-reactors in the same period and located within 5 km from case-farms. Questionnaires were administered for data collection with questions based on epidemiological plausibility and characteristics of the local livestock industry. Data were analyzed using multiple logistic regressions. A significant geographic cluster was identified only in Chiang Mai province (p < 0.05). The risk factor associated with presence of SIT-reactors in dairy herds located in this region was purchasing dairy cows from dealers (OR = 5.85, 95% CI = 1.66–20.58, and p = 0.006). From this study, it was concluded that geographic clustering was identified for dairy farms with SIT-reactors in these provinces, and the cattle movements through cattle dealers increased the risks for SIT-reactor farm status. PMID:28553557

Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus–Associated Pneumonia Among Children Aged <5 Years in the PERCH Study

PubMed Central

Le, Tham; O’Brien, Katherine L.; Murdoch, David R.; Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Scott, J. Anthony G.; Thea, Donald M.; Awori, Juliet O.; Baillie, Vicky L.; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Endtz, Hubert P.; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A.; Moore, David P.; Park, Daniel E.; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D.; Zeger, Scott L.; Deloria Knoll, Maria; Madhi, Shabir A.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fancourt, Nicholas; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Mahomed, Nasreen; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; Wa Somwe, Somwe; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne

2017-01-01

Abstract Background. Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods. We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results. Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. PMID:28575375

Cryptosporidiosis Outbreak Associated With a Single Hotel.

PubMed

Fill, Mary-Margaret A; Lloyd, Jennifer; Chakraverty, Tamal; Sweat, David; Manners, Judy; Garman, Katie; Hlavsa, Michele C; Roellig, Dawn M; Dunn, John R; Schaffner, William; Jones, Timothy F

2017-05-01

We investigated a gastrointestinal illness cluster among persons who attended a baseball tournament (>200 teams) during July 2015. We interviewed representatives of 19 teams; illness was reported among only the 9 (47%) teams that stayed at Hotel A (p < .01). We identified 55 primary cases. A case-control study demonstrated that pool exposure at Hotel A was significantly associated with illness (odds ratio: 7.3; 95% confidence interval: 3.6, 15.2). Eight out of nine (89%) stool specimens tested were positive for Cryptosporidium, with C. hominis IfA12G1 subtype identified in two specimens. The environmental health assessment detected a low free available chlorine level, and pool water tested positive for E. coli and total coliforms. A possible diarrheal contamination event, substantial hotel pool use, and use of cyanuric acid might have contributed to this outbreak and magnitude. Aquatic facilities practicing proper operation and maintenance (e.g., following the Centers for Disease Control and Prevention’s Model Aquatic Health Code) can protect the public’s health.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

PubMed Central

Trifan, Anca; Stanciu, Carol; Girleanu, Irina; Stoica, Oana Cristina; Singeap, Ana Maria; Maxim, Roxana; Chiriac, Stefan Andrei; Ciobica, Alin; Boiculese, Lucian

2017-01-01

AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal. PMID:29085200

Is stress level related to Dengue Hemorrhagic fever cases in Semarang?

NASA Astrophysics Data System (ADS)

Purdianingrum, Julliana; Adib Mubarok, Muhammad; Putri Sunarno, Rahmah; Khairunisa, Ummi; Endah Wahyuningsih, Nur; Murwani, Retno; Budiharjo, Anto

2018-05-01

Dengue Hemorrhagic Fever (DHF) is transmitted to humans by dengue virus harboring Aedes aegypti. Immune response against viral infection can be influenced by stress as stress could weaken immune response. Stress can cause illness through physiological changes and changes in immune function. The immunological changes associated with stress were adapted from the immunological changes in response to infection. The purpose of this study was to determine the relationship between DHF cases with stress level._We used a case control study with DHF sample cases from three hospitals in Semarang city (n=27) from the period of March to May 2017 and the control groups from healthy respondents with matched age, sex, and district location (n=27). The data was processed by Chi-Square test._Levels of stress were categorized into two namely high and low tress levels. The data was normally distributed. The frequency distribution in case group at high stress category were 15 respondents (55.6%) and low stress were 12 respondents (44.4%). Meanwhile, in control group there were 8 respondents (29.6%) at high stress category and 19 respondents (70.4%) at low stress category. The Chi Square Test revealed that the p value was 0,054 and OR was 2,969. In conclusion there was no relation between stress level and Dengue Hemorrhagic Fever cases.

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

PubMed

Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

2010-03-01

We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

Risk factors for Staphylococcus aureus postpartum breast abscess.

PubMed

Branch-Elliman, Westyn; Golen, Toni H; Gold, Howard S; Yassa, David S; Baldini, Linda M; Wright, Sharon B

2012-01-01

Staphylococcus aureus (SA) breast abscesses are a complication of the postpartum period. Risk factors for postpartum SA breast abscesses are poorly defined, and literature is conflicting. Whether risk factors for methicillin-resistant SA (MRSA) and methicillin-susceptible SA (MSSA) infections differ is unknown. We describe novel risk factors associated with postpartum breast abscesses and the changing epidemiology of this infection. We conducted a cohort study with a nested case-control study (n = 216) involving all patients with culture-confirmed SA breast abscess among >30 000 deliveries at our academic tertiary care center from 2003 through 2010. Data were collected from hospital databases and through abstraction from medical records. All SA cases were compared with both nested controls and full cohort controls. A subanalysis was completed to determine whether risk factors for MSSA and MRSA breast abscess differ. Univariate analysis was completed using Student's t test, Wilcoxon rank-sum test, and analysis of variance, as appropriate. A multivariable stepwise logistic regression was used to determine final adjusted results for both the case-control and the cohort analyses. Fifty-four cases of culture-confirmed abscess were identified: 30 MRSA and 24 MSSA. Risk factors for postpartum SA breast abscess in multivariable analysis include in-hospital identification of a mother having difficulty breastfeeding (odds ratio, 5.00) and being a mother employed outside the home (odds ratio, 2.74). Risk factors did not differ between patients who developed MRSA and MSSA infections. MRSA is an increasingly important pathogen in postpartum women; risk factors for postpartum SA breast abscess have not changed with the advent of community-associated MRSA.

Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

PubMed

Oberle, Doris; Pavel, Jutta; Mayer, Geert; Geisler, Peter; Keller-Stanislawski, Brigitte

2017-06-01

Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic Fibrosis.

PubMed

Blue, Elizabeth; Louie, Tin L; Chong, Jessica X; Hebbring, Scott J; Barnes, Kathleen C; Rafaels, Nicholas M; Knowles, Michael R; Gibson, Ronald L; Bamshad, Michael J; Emond, Mary J

2018-04-01

Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal recessive disorder characterized by abnormal mucociliary clearance and obstructive lung disease. We hypothesized that genes underlying the development or function of cilia may modify lung disease severity in persons with cystic fibrosis. To test this hypothesis, we compared variants in 93 candidate genes in both upper and lower tertiles of lung function in a large cohort of children and adults with cystic fibrosis with those of a population control dataset. Variants within candidate genes were tested for association using the SKAT-O test, comparing cystic fibrosis cases defined by poor (n = 127) or preserved (n = 127) lung function with population controls (n = 3,269 or 3,148, respectively). Associated variants were then tested for association with related phenotypes in independent datasets. Variants in DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis, whereas variants in DNAH14 and DNAH6 were associated with preserved lung function in cystic fibrosis. Associations between DNAH14 and lung function were replicated in disease-related phenotypes characterized by obstructive lung disease in adults. Genetic variants within DNAH6, DNAH14, and DNAAF3 are associated with variation in lung function among persons with cystic fibrosis.

U.S. Coast Guard SARSAT Final Evaluation Report. Volume II. Appendices.

DOT National Transportation Integrated Search

1987-03-01

Contents: Controlled Tests; Controlled Test Error Analysis, Processing of Westwind Data; Exercises and Homing Tests; Further Analysis of Controlled Tests; Sar Case Analysis Tables; Narratives of Real Distress Cases; RCC Response Scenarios; Workload A...

Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.

PubMed

Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P; Markus, Hugh S; Lewis, Cathryn M; Scott, Ian C

2017-08-01

To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. A case-control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 - 7 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 - 5 ) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 - 3 ). Gene-environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Student learning outcomes associated with video vs. paper cases in a public health dentistry course.

PubMed

Chi, Donald L; Pickrell, Jacqueline E; Riedy, Christine A

2014-01-01

Educational technologies such as video cases can improve health professions student learning outcomes, but few studies in dentistry have evaluated video-based technologies. The goal of this study was to compare outcomes associated with video and paper cases used in an introductory public health dentistry course. This was a retrospective cohort study with a historical control group. Based on dual coding theory, the authors tested the hypotheses that dental students who received a video case (n=37) would report better affective, cognitive, and overall learning outcomes than students who received a paper case (n=75). One-way ANOVA was used to test the hypotheses across ten cognitive, two affective, and one general assessment measures (α=0.05). Students in the video group reported a significantly higher overall mean effectiveness score than students in the paper group (4.2 and 3.3, respectively; p<0.001). Video cases were also associated with significantly higher mean scores across the remaining twelve measures and were effective in helping students achieve cognitive (e.g., facilitating good discussions, identifying public health problems, realizing how health disparities might impact their future role as dentists) and affective (e.g., empathizing with vulnerable individuals, appreciating how health disparities impact real people) goals. Compared to paper cases, video cases significantly improved cognitive, affective, and overall learning outcomes for dental students.

Pooled Sequencing of 531 Genes in Inflammatory Bowel Disease Identifies an Associated Rare Variant in BTNL2 and Implicates Other Immune Related Genes

PubMed Central

Prescott, Natalie J.; Lehne, Benjamin; Stone, Kristina; Lee, James C.; Taylor, Kirstin; Knight, Jo; Papouli, Efterpi; Mirza, Muddassar M.; Simpson, Michael A.; Spain, Sarah L.; Lu, Grace; Fraternali, Franca; Bumpstead, Suzannah J.; Gray, Emma; Amar, Ariella; Bye, Hannah; Green, Peter; Chung-Faye, Guy; Hayee, Bu’Hussain; Pollok, Richard; Satsangi, Jack; Parkes, Miles; Barrett, Jeffrey C.; Mansfield, John C.; Sanderson, Jeremy; Lewis, Cathryn M.; Weale, Michael E.; Schlitt, Thomas; Mathew, Christopher G.

2015-01-01

The contribution of rare coding sequence variants to genetic susceptibility in complex disorders is an important but unresolved question. Most studies thus far have investigated a limited number of genes from regions which contain common disease associated variants. Here we investigate this in inflammatory bowel disease by sequencing the exons and proximal promoters of 531 genes selected from both genome-wide association studies and pathway analysis in pooled DNA panels from 474 cases of Crohn’s disease and 480 controls. 80 variants with evidence of association in the sequencing experiment or with potential functional significance were selected for follow up genotyping in 6,507 IBD cases and 3,064 population controls. The top 5 disease associated variants were genotyped in an extension panel of 3,662 IBD cases and 3,639 controls, and tested for association in a combined analysis of 10,147 IBD cases and 7,008 controls. A rare coding variant p.G454C in the BTNL2 gene within the major histocompatibility complex was significantly associated with increased risk for IBD (p = 9.65x10−10, OR = 2.3[95% CI = 1.75–3.04]), but was independent of the known common associated CD and UC variants at this locus. Rare (<1%) and low frequency (1–5%) variants in 3 additional genes showed suggestive association (p<0.005) with either an increased risk (ARIH2 c.338-6C>T) or decreased risk (IL12B p.V298F, and NICN p.H191R) of IBD. These results provide additional insights into the involvement of the inhibition of T cell activation in the development of both sub-phenotypes of inflammatory bowel disease. We suggest that although rare coding variants may make a modest overall contribution to complex disease susceptibility, they can inform our understanding of the molecular pathways that contribute to pathogenesis. PMID:25671699

Sequence variants of Toll-like receptor 4 and susceptibility to prostate cancer.

PubMed

Chen, Yen-Ching; Giovannucci, Edward; Lazarus, Ross; Kraft, Peter; Ketkar, Shamika; Hunter, David J

2005-12-15

Chronic inflammation has been hypothesized to be a risk factor for prostate cancer. The Toll-like receptor 4 (TLR4) presents the bacterial lipopolysaccharide (LPS), which interacts with ligand-binding protein and CD14 (LPS receptor) and activates expression of inflammatory genes through nuclear factor-kappaB and mitogen-activated protein kinase signaling. A previous case-control study found a modest association of a polymorphism in the TLR4 gene [11381G/C, GG versus GC/CC: odds ratio (OR), 1.26] with risk of prostate cancer. We assessed if sequence variants of TLR4 were associated with the risk of prostate cancer. In a nested case-control design within the Health Professionals Follow-up Study, we identified 700 participants with prostate cancer diagnosed after they had provided a blood specimen in 1993 and before January 2000. Controls were 700 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped 16 common (>5%) single nucleotide polymorphisms (SNP) discovered in a resequencing study spanning TLR4 to test for association between sequence variation in TLR4 and prostate cancer. Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29). Six common haplotypes (cumulative frequency, 81%) were observed; the global test for association between haplotypes and prostate cancer was statistically significant (chi(2) = 14.8 on 6 degrees of freedom; P = 0.02). Two common haplotypes were statistically significantly associated with altered risk of prostate cancer. Inherited polymorphisms of the innate immune gene TLR4 are associated with risk of prostate cancer.

Nested Event-Level Case-Control Study of Drug Use and Sexual Outcomes in Multipartner Encounters Reported by Men Who Have Sex with Men.

PubMed

Melendez-Torres, G J; Hickson, Ford; Reid, David; Weatherburn, Peter; Bonell, Chris

2016-03-01

Previous event-level analyses have often, but not always, found significant associations between drug use and sexual risk behaviour in men who have sex with men (MSM), but these analyses have rarely considered either multipartner encounters specifically, or other sexual outcomes such as pleasure and control. Using data from an internet-based longitudinal survey of MSM, we tested the association between drug use by respondent and by partners and unprotected anal intercourse (UAI), pleasure and control over sexual activity. Overall respondent substance use was significantly associated with increased odds of UAI, though not with pleasure or control. Respondent use of crystal methamphetamine was significantly associated with both increased odds of UAI and decreased odds of control over sexual activity. This analysis agrees with previous studies of dyadic encounters, and specifically suggests that the association between crystal methamphetamine and sexual risk behaviour may be mediated by loss of control.

The Human Ortholog of Acid-Sensing Ion Channel Gene ASIC1a Is Associated With Panic Disorder And Amygdala Structure And Function

PubMed Central

Smoller, Jordan W.; Gallagher, Patience J.; Duncan, Laramie E.; McGrath, Lauren M.; Haddad, Stephen A.; Holmes, Avram.; Wolf, Aaron B.; Hilker, Sidney; Block, Stefanie R.; Weill, Sydney; Young, Sarah; Choi, Eun Young; Rosenbaum, Jerrold F.; Biederman, Joseph; Faraone, Stephen V.; Roffman, Joshua; Manfro, Gisele G.; Blaya, Carolina; Hirshfeld-Becker, Dina R.; Stein, Murray B.; Van Ameringen, Michael; Tolin, David F.; Otto, Michael W.; Pollack, Mark H.; Simon, Naomi M.; Buckner, Randy L.; Ongur, Dost; Cohen, Bruce M.

2014-01-01

Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD. PMID:24529281

Neurocognitive dysfunction in children with β thalassemia major: psychometric, neurophysiologic and radiologic evaluation.

PubMed

Elalfy, M S; Aly, R H; Azzam, H; Aboelftouh, K; Shatla, R H; Tarif, M; Abdatty, M; Elsayed, R M

2017-12-01

To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS). WISC in our study showed that 40% of cases were borderline mental function as regards total IQ. Neurophysiologic tests were significantly impaired in patients compared to control group, with significant impairment in those receiving desferrioxamine (DFO). P300 amplitude was significantly lower in cases compared to controls (2.24 and 4.66 uv, respectively), recording the shortest amplitude in patients receiving DFO. Altered metabolic markers in the brain were detected by MRS in the form of reduced N-acetylaspartate to creatine ratio in 78.3% of our cases. There were significant correlations between psychometric tests and both neurophysiologic (P300) and radiologic (MRS) tests. β-TM is associated with neurocognitive impairment that can be assessed by psychometric, neurophysiologic and radiologic tests. The role of hemosiderosis and iron chelation therapy on cognitive functioning still need more research. β-TM: beta thalassemia major; DFO: Dysferal; DFP: Deferiprone; DFX: Deferasirox; WISC: Wechsler Intelligence Scale for Children; VIQ: verbal IQ; PIQ: performance IQ; TIQ: total IQ; BVRT: Benton Visual Retention Test; WCST: Wisconsin Card Sort Test; MRS: Magnetic resonant spectroscopy; NAA/Cr ratio: N-acetylaspartate to creatine ratio.

Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.

PubMed

Saxena, R; Georgopoulos, N A; Braaten, T J; Bjonnes, A C; Koika, V; Panidis, D; Welt, C K

2015-06-01

Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women? One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity. Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits. The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls). Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits. A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test. The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS. This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations. The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals. NCT00166569. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

PubMed Central

Haiman, Christopher A; Chen, Gary K; Vachon, Celine M; Canzian, Federico; Dunning, Alison; Millikan, Robert C; Wang, Xianshu; Ademuyiwa, Foluso; Ahmed, Shahana; Ambrosone, Christine B; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V; Beckmann, Matthias W; Berg, Christine D; Bernstein, Leslie; Blomqvist, Carl; Blot, William J; Brauch, Hiltrud; Buring, Julie E; Carey, Lisa A; Carpenter, Jane E; Chang-Claude, Jenny; Chanock, Stephen J; Chasman, Daniel I; Clarke, Christine L; Cox, Angela; Cross, Simon S; Deming, Sandra L; Diasio, Robert B; Dimopoulos, Athanasios M; Driver, W Ryan; Dünnebier, Thomas; Durcan, Lorraine; Eccles, Diana; Edlund, Christopher K; Ekici, Arif B; Fasching, Peter A; Feigelson, Heather S; Flesch-Janys, Dieter; Fostira, Florentia; Försti, Asta; Fountzilas, George; Gerty, Susan M; Giles, Graham G; Godwin, Andrew K; Goodfellow, Paul; Graham, Nikki; Greco, Dario; Hamann, Ute; Hankinson, Susan E; Hartmann, Arndt; Hein, Rebecca; Heinz, Judith; Holbrook, Andrea; Hoover, Robert N; Hu, Jennifer J; Hunter, David J; Ingles, Sue A; Irwanto, Astrid; Ivanovich, Jennifer; John, Esther M; Johnson, Nicola; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Ko, Yon-Dschun; Kolonel, Laurence N; Konstantopoulou, Irene; Kosma, Veli-Matti; Kulkarni, Swati; Lambrechts, Diether; Lee, Adam M; Le Marchand, Loïc; Lesnick, Timothy; Liu, Jianjun; Lindstrom, Sara; Mannermaa, Arto; Margolin, Sara; Martin, Nicholas G; Miron, Penelope; Montgomery, Grant W; Nevanlinna, Heli; Nickels, Stephan; Nyante, Sarah; Olswold, Curtis; Palmer, Julie; Pathak, Harsh; Pectasides, Dimitrios; Perou, Charles M; Peto, Julian; Pharoah, Paul D P; Pooler, Loreall C; Press, Michael F; Pylkäs, Katri; Rebbeck, Timothy R; Rodriguez-Gil, Jorge L; Rosenberg, Lynn; Ross, Eric; Rüdiger, Thomas; Silva, Isabel dos Santos; Sawyer, Elinor; Schmidt, Marjanka K; Schulz-Wendtland, Rüdiger; Schumacher, Fredrick; Severi, Gianluca; Sheng, Xin; Signorello, Lisa B; Sinn, Hans-Peter; Stevens, Kristen N; Southey, Melissa C; Tapper, William J; Tomlinson, Ian; Hogervorst, Frans B L; Wauters, Els; Weaver, JoEllen; Wildiers, Hans; Winqvist, Robert; Van Den Berg, David; Wan, Peggy; Xia, Lucy Y; Yannoukakos, Drakoulis; Zheng, Wei; Ziegler, Regina G; Siddiq, Afshan; Slager, Susan L; Stram, Daniel O; Easton, Douglas; Kraft, Peter; Henderson, Brian E; Couch, Fergus J

2012-01-01

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10−10). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10−9), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10−9). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations. PMID:22037553

An outbreak investigation of scrub typhus in Western Province, Solomon Islands, 2014.

PubMed

Marks, Michael; Joshua, Cynthia; Longbottom, Jenny; Longbottom, Katherine; Sio, Alison; Puiahi, Elliot; Jilini, Greg; Stenos, John; Dalipanda, Tenneth; Musto, Jennie

2016-01-01

To identify the etiology and risk factors of undifferentiated fever in a cluster of patients in Western Province, Solomon Islands, May 2014. An outbreak investigation with a case control study was conducted. A case was defined as an inpatient in one hospital in Western Province, Solomon Islands with high fever (> 38.5 °C) and a negative malaria microscopy test admitted between 1 and 31 May 2014. Asymptomatic controls matched with the cases residentially were recruited in a ratio of 1:2. Serum samples from the subjects were tested for rickettsial infections using indirect micro-immunofluorescence assay. Nine cases met the outbreak case definition. All cases were male. An eschar was noted in five cases (55%), and one developed pneumonitis. We did not identify any environmental factors associated with illness. Serum samples of all five follow-up cases (100%) had strong-positive IgG responses to scrub typhus. All but one control (10%) had a moderate response against scrub typhus. Four controls had low levels of antibodies against spotted fever group rickettsia, and only one had a low-level response to typhus group rickettsia. This outbreak represents the first laboratory-confirmed outbreak of scrub typhus in the Western Province of Solomon Islands. The results suggest that rickettsial infections are more common than currently recognized as a cause of an acute febrile illness. A revised clinical case definition for rickettsial infections and treatment guidelines were developed and shared with provincial health staff for better surveillance and response to future outbreaks of a similar kind.

A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children

PubMed Central

Arthur, Jane L.; Higgins, Geoffrey D.; Davidson, Geoffrey P.; Givney, Rodney C.; Ratcliff, Rodney M.

2009-01-01

Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemar's Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study. PMID:19381259

[Anaphylaxis related to measles, mumps, and rubella vaccine in Santa Catarina State, Brazil, 2014 and 2015].

PubMed

Fantinato, Francieli Fontana Sutile Tardetti; Vargas, Alexander; Carvalho, Sandra Maria Deotti; Domingues, Carla Magda Allan Santos; Barreto, Gisele; Fialho, Arieli Schiessl; Silva, Roselita Heinen da; Saad, Eduardo; Agredo, Ivonne Natalia Solarte

2018-03-12

The study aimed to describe cases and verify the frequency of anaphylaxis related to measles, mumps, and rubella (MMR) vaccine produced by manufacturer A and to assess associated risk factors. This was a case-control study (1:4) in Santa Catarina State, Brazil, from July 14, 2014, to January 12, 2015, in children from one year to less than five years of age, vaccinated with MMR and reported with anaphylaxis, while the controls were without anaphylaxis. The measure of association was odds ratio (OR) with 95% confidence interval (95%CI), using the chi-square and Fisher's exact tests. Anaphylaxis rates were calculated per doses distributed/administered. Fifteen cases and 60 controls were interviewed in 12 municipalities (counties). Anaphylaxis rates were 2.46 and 5.05 cases per 100,000 doses distributed and administered, respectively. Among the cases of anaphylaxis, eight (53.4%) were males, and among the controls, 36 (60%), with p = 0.64. The bivariate analysis of anaphylaxis and cow's milk protein allergy (CMPA) showed OR = 51.62, with p = 0.00002 and 95%CI: 5.59-476.11. The variables family food allergy, breastfeeding, previous post-vaccine adverse event (PVAE), and simultaneous vaccination were not statistically significant (p = 0.48; p = 1.00; p = 0.49; p = 0.61). Anaphylaxis rates per doses distributed/administered exceeded 1/100,000 doses administered (expected rate). Anaphylaxis and CMPA showed a statistically significant association. No statistically significant associations were found with simultaneous vaccination, breastfeeding, family food allergy, or history of PVAE. the manufacturer should specify the product's components in the package insert, and children with a history of CMPA should not be vaccinated with this vaccine.

A nationwide study of the association between celiac disease and the risk of autistic spectrum disorders.

PubMed

Ludvigsson, Jonas F; Reichenberg, Abraham; Hultman, Christina M; Murray, Joseph A

2013-11-01

Most case reports suggest an association between autistic spectrum disorders (ASDs) and celiac disease (CD) or positive CD serologic test results, but larger studies are contradictory. To examine the association between ASDs and CD according to small intestinal histopathologic findings. Nationwide case-control study in Sweden. Through 28 Swedish biopsy registers, we collected data about 26,995 individuals with CD (equal to villous atrophy, Marsh stage 3), 12,304 individuals with inflammation (Marsh stages 1-2), and 3719 individuals with normal mucosa (Marsh stage 0) but positive CD serologic test results (IgA/IgG gliadin, endomysium, or tissue transglutaminase) and compared them with 213,208 age- and sex-matched controls. Conditional logistic regression estimated odds ratios (ORs) for having a prior diagnosis of an ASD according to the Swedish National Patient Register. In another analysis, we used the Cox proportional hazards regression model to estimate hazard ratios (HRs) for future ASDs in individuals undergoing small intestinal biopsy. A prior ASD was not associated with CD (OR, 0.93; 95% CI, 0.51-1.68) or inflammation (OR 1.03; 95% CI, 0.40-2.64) but was associated with a markedly increased risk of having a normal mucosa but a positive CD serologic test result (OR, 4.57; 95% CI, 1.58-13.22). Restricting our data to individuals without a diagnosis of an ASD at the time of biopsy, CD (HR, 1.39; 95% CI, 1.13-1.71) and inflammation (HR, 2.01; 95% CI, 1.29-3.13) were both associated with moderate excess risks of later ASDs, whereas the HR for later ASDs in individuals with normal mucosa but positive CD serologic test results was 3.09 (95% CI, 1.99-4.80). Although this study found no association between CD or inflammation and earlier ASDs, there was a markedly increased risk of ASDs in individuals with normal mucosa but a positive CD serologic test result.

Large Outbreak of Hepatitis C Virus Associated With Drug Diversion by a Healthcare Technician.

PubMed

Alroy-Preis, Sharon; Daly, Elizabeth R; Adamski, Christine; Dionne-Odom, Jodie; Talbot, Elizabeth A; Gao, Fengxiang; Cavallo, Steffany J; Hansen, Katrina; Mahoney, Jennifer C; Metcalf, Erin; Loring, Carol; Bean, Christine; Drobeniuc, Jan; Xia, Guo-Liang; Kamili, Saleem; Montero, José T

2018-05-14

In May 2012, the New Hampshire (NH) Division of Public Health Services (DPHS) was notified of 4 persons with newly diagnosed hepatitis C virus (HCV) infection at hospital X. Initial investigation suggested a common link to the hospital cardiac catheterization laboratory (CCL) because the infected persons included 3 CCL patients and a CCL technician. NH DPHS initiated an investigation to determine the source and control the outbreak. NH DPHS conducted site visits, case patient and employee interviews, medical record and medication use review, and employee and patient HCV testing using enzyme immunoassay for anti-HCV, reverse-transcription polymerase chain reaction for HCV RNA, nonstructural 5B (NS5B) and hypervariable region 1 (HVR1) sequencing, and quasispecies analysis. HCV HVR1 analysis of the first 4 cases confirmed a common source of infection. HCV testing identified 32 of 1074 CCL patients infected with the outbreak strain, including 3 patients coinfected with >1 HCV strain. The epidemiologic investigation revealed evidence of drug diversion by the HCV-infected technician, evidenced by gaps in controlled medication control, higher fentanyl use during procedures for confirmed cases, and building card key access records documenting the presence of the technician during days when transmission occurred. The employee's status as a traveling technician led to a multistate investigation, which identified additional cases at prior employment sites. This is the largest laboratory-confirmed drug diversion-associated HCV outbreak published to date. Recommendations to reduce drug diversion risk and to conduct outbreak investigations are provided.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Study of cognitive functions in newly diagnosed cases of subclinical and clinical hypothyroidism.

PubMed

Sharma, Kirti; Behera, Joshil Kumar; Sood, Sushma; Rajput, Rajesh; Satpal; Praveen, Prashant

2014-01-01

Hypothyroidism is associated with significant neurocognitive deficits because hypothyroidism prevents the brain from adequately sustaining the energy consuming processes needed for neurotransmission, memory, and other higher brain functions. Hence, the study was done to assess the cognitive functions of newly diagnosed subclinical and clinical hypothyroid patients by evoked response potential P300. 75 patients each of newly diagnosed subclinical and clinical hypothyroid patients attending endocrinology clinic and 75 healthy age and sex matched euthyroid controls were considered for the study. P300 was recorded with Record Medicare System Polyrite, Chandigarh using auditory "oddball paradigm". The data was analyzed using ANOVA followed by post Tukey's test. Newly diagnosed clinical hypothyroid patients showed a significant increase in P300 latency compared to control (P < 0.05) and subclinical cases (P < 0.01) while there was no significant difference between the P300 latency of subclinical cases and control group. Also, there was no significant difference in P300 amplitude among the three groups. P300 latency in case of newly diagnosed hypothyroid clinical cases is significantly increased compared to newly diagnosed subclinical cases and control.

Rituximab associated neutropenia: Description of three cases and an insight into the underlying pathogenesis

PubMed Central

Weissmann-Brenner, Alina; Brenner, Baruch; Belyaeva, Inessa; Lahav, Meir; Rabizadeh, Esther

2011-01-01

Summary Background To describe Rituximab associated neutropenia (RAN), and to explore its underlying mechanism. Case Report We describe three patients with RAN. The effect of patient’s plasma on colony forming unit, Granulocyte-Monocyte (CFU-GM) was measured by the addition of plasma to the culture of a healthy bone-marrow. Repeated tests were performed after recovery of white count. In the leukopenic period the patient’s plasma inhibited CFU growth completely. Control plasma did not have such an effect. Addition of patient’s cell supernatant to bone marrow cells did not change the number of CFU. The same effect was demonstrated in normal control. After recovery the patient’s plasma did not inhibit colony formation, similar to control. Conclusions RAN is a clinically significant side effect. It may take place during treatment or several months afterwards. Circulating antibodies in the plasma may be responsible for this unique BM toxicity. PMID:22037749

Health costs of economic expansion: the case of manufacturing accident injuries.

PubMed Central

Catalano, R

1979-01-01

The hypothesized relationship between economic expansion and accident injuries is tested using archival economic and accident data from the Los Angeles-Long Beach, California metropolitan area. The association is measured using cross-correlation techniques after variation shared with a comparison metropolitan area (Anaheim-Santa Ana-Garden Grove) is removed. Two tests of association are conducted. The first uses the raw accident rate of the comparison metropolitan area as a control variable while the second adjusts the control variable to reflect shared industrial sectors. Findings suggest that the incidence of disabling accidents increases in the month before and during the month that the manufacturing work force expands. The impact appears strongest during the month that new workers are added. PMID:453412

Domains of unprofessional behavior during medical school associated with future disciplinary action by a state medical board.

PubMed

Teherani, Arianne; Hodgson, Carol S; Banach, Mary; Papadakis, Maxine A

2005-10-01

In a previous study, we showed that unprofessional behavior in medical school was associated with subsequent disciplinary action. This study expands on that work by identifying the domains of unprofessional behavior that are most problematic. In this retrospective case-control study, negative comments were extracted from student files for 68 case (disciplined) and 196 matched control (nondisciplined) physicians. Comments were analyzed qualitatively and subsequently quantified. The relationship between domains of behavior and disciplinary action was established through chi-square tests and multivariate analysis of variance. Three domains of unprofessional behavior emerged that were related significantly to later disciplinary outcome: (1) poor reliability and responsibility, (2) lack of self-improvement and adaptability, and (3) poor initiative and motivation. Three critical domains of professionalism associated with future disciplinary action have been defined. These findings could lead to focused remediation strategies and policy decisions.

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease

PubMed Central

Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Choi, Seung-Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez-Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O’Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li-san; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

2013-01-01

Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease. PMID:24162737

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

PubMed

Keogh, Ruth H; Mangtani, Punam; Rodrigues, Laura; Nguipdop Djomo, Patrick

2016-01-05

Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

Association between global DNA hypomethylation in leukocytes and risk of breast cancer.

PubMed

Choi, Ji-Yeob; James, Smitha R; Link, Petra A; McCann, Susan E; Hong, Chi-Chen; Davis, Warren; Nesline, Mary K; Ambrosone, Christine B; Karpf, Adam R

2009-11-01

Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Samples and data were obtained from women with incident early-stage breast cancer (I-IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case-control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84-2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65-4.94) had higher risk of breast cancer (P for trend < or = 0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.

A Tissue Systems Pathology Test Detects Abnormalities Associated with Prevalent High-Grade Dysplasia and Esophageal Cancer in Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Davison, Jon M; Prichard, Jeffrey W; Reese, Lia M; Zhang, Yi; Repa, Kathleen; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory G; DeMarshall, Maureen; Foxwell, Tyler; Jobe, Blair A; Zaidi, Ali H; Duits, Lucas C; Bergman, Jacques J G H M; Rustgi, Anil; Falk, Gary W

2017-02-01

There is a need for improved tools to detect high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. In previous work, we demonstrated that a 3-tier classifier predicted risk of incident progression in Barrett's esophagus. Our aim was to determine whether this risk classifier could detect a field effect in nondysplastic (ND), indefinite for dysplasia (IND), or low-grade dysplasia (LGD) biopsies from Barrett's esophagus patients with prevalent HGD/EAC. We performed a multi-institutional case-control study to evaluate a previously developed risk classifier that is based upon quantitative image features derived from 9 biomarkers and morphology, and predicts risk for HGD/EAC in Barrett's esophagus patients. The risk classifier was evaluated in ND, IND, and LGD biopsies from Barrett's esophagus patients diagnosed with HGD/EAC on repeat endoscopy (prevalent cases, n = 30, median time to HGD/EAC diagnosis 140.5 days) and nonprogressors (controls, n = 145, median HGD/EAC-free surveillance time 2,015 days). The risk classifier stratified prevalent cases and non-progressor patients into low-, intermediate-, and high-risk classes [OR, 46.0; 95% confidence interval, 14.86-169 (high-risk vs. low-risk); P < 0.0001]. The classifier also provided independent prognostic information that outperformed the subspecialist and generalist diagnosis. A tissue systems pathology test better predicts prevalent HGD/EAC in Barrett's esophagus patients than pathologic variables. The results indicate that molecular and cellular changes associated with malignant transformation in Barrett's esophagus may be detectable as a field effect using the test. A tissue systems pathology test may provide an objective method to facilitate earlier identification of Barrett's esophagus patients requiring therapeutic intervention. Cancer Epidemiol Biomarkers Prev; 26(2); 240-8. ©2016 AACR. ©2016 American Association for Cancer Research.

Interleukin 12B (IL12B) Genetic Variation and Pulmonary Tuberculosis: A Study of Cohorts from The Gambia, Guinea-Bissau, United States and Argentina

PubMed Central

Hill, Philip C.; Wejse, Christian; Bisseye, Cyrille; Olesen, Rikke; Edwards, Todd L.; Gilbert, John R.; Myers, Jamie L.; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Hamilton, Carol D.; Tacconelli, Alessandra; Novelli, Giuseppe; Brunetti, Ercole; Aaby, Peter; Sodemann, Morten; Østergaard, Lars; Adegbola, Richard; Williams, Scott M.; Scott, William K.; Sirugo, Giorgio

2011-01-01

We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3′ UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58–1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61–1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it. PMID:21339808

Toxicology Testing in Fatally Injured Workers: A Review of Five Years of Iowa FACE Cases

PubMed Central

Ramirez, Marizen; Bedford, Ronald; Sullivan, Ryan; Anthony, T. Renee; Kraemer, John; Faine, Brett; Peek-Asa, Corinne

2013-01-01

Toxicology testing of fatally injured workers is not routinely conducted. We completed a case-series study of 2005–2009 occupational fatalities captured by Iowa’s Fatality Assessment and Control Evaluation (FACE) Program. The goals of our research were to: (1) measure the proportion of FACE cases that undergo toxicology testing, and describe the factors associated with being tested, and (2) measure the rate of positive toxicology tests, the substances identified and the demographics and occupations of victims who tested positive. Case documents and toxicology laboratory reports were reviewed. There were 427 occupational deaths from 2005 to 2009. Only 69% underwent toxicology testing. Younger workers had greater odds of being tested. Among occupational groups, workers in farming, fishing and forestry had half the odds of being tested compared to other occupational groups. Of the 280 cases with toxicology tests completed, 22% (n = 61) were found to have positive toxicology testing. Commonly identified drug classes included cannabinoids and alcohols. Based on the small number of positive tests, older victims (65+ years) tested positive more frequently than younger workers. Management, business, science, arts, service and sales/office workers had proportionately more positive toxicology tests (almost 30%) compared with other workers (18–22%). These results identify an area in need of further research efforts and a potential target for injury prevention strategies. PMID:24240727

[Risk factors associated with bacterial growth in derivative systems from cerebrospinal liquid in pediatric patients].

PubMed

de Jesús Vargas-Lares, José; Andrade-Aguilera, Angélica Rocío; Díaz-Peña, Rafael; Barrera de León, Juan Carlos

2015-01-01

To determine risk factors associated with bacterial growth in systems derived from cerebrospinal fluid in pediatric patients. Case and controls study from January to December 2012, in patients aged <16 years who were carriers of hydrocephalus and who required placement or replacement of derivative system. Cases were considered as children with cultures with bacterial growth and controls with negative bacterial growth. Inferential statistics with Chi-squared and Mann-Whitney U tests. Association of risk with odds ratio. We reviewed 746 registries, cases n=99 (13%) and controls n=647 (87%). Masculine gender 58 (57%) vs. feminine gender 297 (46%) (p=0.530). Age of cases: median, five months and controls, one year (p=0.02). Median weight, 7 vs. 10 kg (p=0.634). Surgical interventions: median n=2 (range, 1-8) vs. n=1 (range, 1-7). Infection rate, 13.2%. Main etiology ductal stenosis, n=29 (29%) vs. n=50 (23%) (p=0.530). Non-communicating, n=50 (51%) vs. 396 (61%) (p=0.456). Predominant microorganisms: enterobacteria, pseudomonas, and enterococcus. Non-use of iodized dressing OR=2.6 (range, 1.8-4.3), use of connector OR=6.8 (range, 1.9-24.0), System replacement OR=2.0 (range, 1.3-3.1), assistant without surgical facemask OR=9.7 (range, 2.3-42.0). Being a breastfeeding infant, of low weight, non-application of iodized dressing, use of connector, previous derivation, and lack of adherence to aseptic technique were all factors associated with ependymitis.

No role for human papillomavirus infection in oral cancers in a region in southern India.

PubMed

Laprise, Claudie; Madathil, Sreenath A; Allison, Paul; Abraham, Priya; Raghavendran, Anantharam; Shahul, Hameed P; ThekkePurakkal, Akhil-Soman; Castonguay, Geneviève; Coutlée, François; Schlecht, Nicolas F; Rousseau, Marie-Claude; Franco, Eduardo L; Nicolau, Belinda

2016-02-15

Oral cancer is a major public health issue in India with ∼ 77,000 new cases and 52,000 deaths yearly. Paan chewing, tobacco and alcohol use are strong risk factors for this cancer in India. Human papillomaviruses (HPVs) are also related to a subset of head and neck cancers (HNCs). We examined the association between oral HPV and oral cancer in a sample of Indian subjects participating in a hospital-based case-control study. We recruited incident oral cancer cases (N = 350) and controls frequency-matched by age and sex (N = 371) from two main referral hospitals in Kerala, South India. Sociodemographic and behavioral data were collected by interviews. Epithelial cells were sampled using Oral CDx® brushes from the oral cancer site and the normal mucosa. Detection and genotyping of 36 HPV genotypes were done using a polymerase chain reaction protocol. Data collection procedures were performed by qualified dentists via a detailed protocol with strict quality control, including independent HPV testing in India and Canada. HPV DNA was detected in none of the cases or controls. Associations between oral cancer and risk factors usually associated with HPV infection, such as oral sex and number of lifetime sexual partners, were examined by logistic regression and were not associated with oral cancer. Lack of a role for HPV infection in this study may reflect cultural or religious characteristics specific to this region in India that are not conducive to oral HPV transmission. A nationwide representative prevalence study is needed to investigate HPV prevalence variability among Indian regions. © 2015 UICC.

Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies.

PubMed

Li, Fei; Zhu, Ce; Deng, Feng-Ying; Wong, May Chun Mei; Lu, Hai-Xia; Feng, Xi-Ping

2017-01-01

Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP. We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias. Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.

Sleep architecture and obstructive sleep apnea in obese children with and without metabolic syndrome: a case control study.

PubMed

Jalilolghadr, Shabnam; Yazdi, Zohreh; Mahram, Manoochehr; Babaei, Farkhondeh; Esmailzadehha, Neda; Nozari, Hoormehr; Saffari, Fatemeh

2016-05-01

Obesity and biochemical parameters of metabolic disorders are both closely related to obstructive sleep apnea (OSA). The aim of this study was to compare sleep architecture and OSA in obese children with and without metabolic syndrome. Forty-two children with metabolic syndrome were selected as case group and 38 children without metabolic syndrome were matched for age, sex, and BMI as control group. The standardized Persian version of bedtime problems, excessive daytime sleepiness, awakenings during the night, regularity and duration of sleep, snoring (BEARS) and Children's Sleep Habits Questionnaires were completed, and polysomnography (PSG) was performed for all study subjects. Scoring was performed using the manual of American Academy of Sleep Medicine for children. Data were analyzed using chi-square test, T test, Mann-Whitney U test, and logistic regression analysis. Non-rapid eye movement (NREM) sleep and N1 stage in the case group were significantly longer than the control group, while REM sleep was significantly shorter. Waking after sleep onset (WASO) was significantly different between two groups. Severe OSA was more frequent in the control group. Multivariate logistic regression analysis showed that severe OSA (OR 21.478, 95 % CI 2.160-213.600; P = 0.009) and REM sleep (OR 0.856, 95 % CI 0.737-0.994; P = 0.041) had independent association with metabolic syndrome. Obese children with metabolic syndrome had increased WASO, N1 sleep stage, and severe OSA. But the results regarding sleep architecture are most likely a direct result of OSA severity. More longitudinal studies are needed to confirm the association of metabolic syndrome and OSA.

Association between interleukin 10 gene -1082 A/G polymorphism and the risk of type 2 diabetes mellitus: a meta-analysis of 4250 subjects.

PubMed

Yin, Yan-Wei; Hu, Ai-Min; Sun, Qian-Qian; Zhang, Bei-Bei; Liu, Hong-Li; Wang, Qi; Zeng, Yi-Hua; Xu, Rui-Jia; Zhang, Shi-Jie; Shi, Long-Bao

2013-05-01

Increasing evidence suggests that interleukin 10 (IL 10) gene -1082 A/G (rsl800896) polymorphism may be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, the results are inconsistent. The aim of this study is to analyze the association between this variant and the T2DM risk by meta-analysis. PubMed, Embase, Web of Science, and Google Scholar were searched from January 1, 1989 to February 17, 2012, as well as hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. Seven case-control studies were identified, covering a total of 1879 T2DM cases and 2371 controls. The results showed evidence of significant association between IL 10 gene -1082 A/G polymorphism and T2DM risk (for G/G+G/A vs. A/A: OR=1.21, 95% CI=1.05-1.40, p=0.010, p=0.040 after Bonferroni testing). In the subgroup analysis by ethnicity, no significant association was found between IL 10 gene -1082 A/G polymorphism and T2DM risk in Europeans. In summary, results from this meta-analysis provide evidence that IL 10 gene -1082 G allele is associated with increased risk of T2DM. Copyright © 2013 Elsevier Ltd. All rights reserved.

The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits.

PubMed

Freitag, Christine M; Lempp, Thomas; Nguyen, T Trang; Jacob, Christian P; Weissflog, Lena; Romanos, Marcel; Renner, Tobias J; Walitza, Susanne; Warnke, Andreas; Rujescu, Dan; Lesch, Klaus-Peter; Reif, Andreas

2016-08-01

Previous linkage and genome wide association (GWA) studies in ADHD indicated astrotactin 2 (ASTN2) as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). ASTN2 plays a key role in glial-guided neuronal migration. To investigate whether common variants in ASTN2 contribute to ADHD disorder risk, we tested 63 SNPs spanning ASTN2 for association with ADHD and specific comorbid disorders in two samples: 171 families of children with ADHD and their parents (N = 592), and an adult sample comprising 604 adult ADHD cases and 974 controls. The C-allele of rs12376789 in ASTN2 nominally increased the risk for ADHD in the trio sample (p = 0.025). This was not observed in the adult case-control sample alone, but retained in the combined sample (nominal p = 0.030). Several other SNPs showed nominally significant association with comorbid disorders, especially anxiety disorder, in the childhood and adult ADHD samples. Some ASTN2 variants were nominally associated with personality traits in the adult ADHD sample and overlapped with risk alleles for comorbid disorders in childhood. None of the findings survived correction for multiple testing, thus, results do not support a major role of common variants in ASTN2 in the pathogenesis of ADHD, its comorbid disorders or ADHD associated personality traits.

Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study.

PubMed

Wyller, Vegard B; Helland, Ingrid B

2013-02-07

Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies. We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome. 38 CFS patients aged 12-18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.

Umbilical Cord Blood pH in Intrapartum Hypoxia.

PubMed

Perveen, Fouzia; Khan, Ayesha; Ali, Tahmina; Rabia, Syeda

2015-09-01

To determine the association of cord arterial blood pH with neonatal outcome in cases of intrapartum fetal hypoxia. Descriptive analytical study. Gynaecology Unit-II, Civil Hospital, Karachi, from September 2011 to November 2012. All singleton cephalic fetuses at term gestation were included in the study. Those with any anomaly, malpresentation, medical disorders, maternal age < 18 years, multiple gestation and ruptured membranes were excluded. Patients with abnormal cardiotocography and/or meconium stained liquor were enrolled as index case and immediate next delivery with no such signs as a control. Demographic characteristics, pH level < or > 7.25, neonatal outcome measures (healthy, NICU admission or neonatal death), color of liquor and mode of delivery recorded on predesigned proforma. Statistical analysis performed by SPSS 16 by using independent-t test or chi-square test and ANOVA test as needed. A total of 204 newborns were evaluated. The mean pH level was found to be significantly different (p=0.007) in two groups. The pH value 7.25 had significant association (p < 0.001) with the neonatal outcome. However, the association of neonatal outcome with severity of acidemia was not found to be significant. Grading of Meconium Stained Liquor (MSL) also did not relate positively with pH levels as 85.7% of grade I, 68.9% of grade II and 59.4% of grade III MSLhad pH > 7.25. Majority (63.6%) cases needed caesarean section as compared to 31.4% controls. There is a significant association of cord arterial blood pH at birth with neonatal outcome at pH < or > 7.25; but below the level of pH 7.25 it is still inconclusive.

Passenger behaviors associated with norovirus infection on board a cruise ship--Alaska, May to June 2004.

PubMed

Chimonas, Marc-Andre R; Vaughan, George H; Andre, Zandra; Ames, Jaret T; Tarling, Grant A; Beard, Suzanne; Widdowson, Marc-Alain; Cramer, Elaine

2008-01-01

During May 2004, the Vessel Sanitation Program (VSP) investigated an outbreak of norovirus gastroenteritis on board a cruise ship sailing in Alaska waters. The objectives were to identify a common food item source and explore behavioral risk factors for person-to-person transmission among passengers. A case was defined as three or more episodes of loose stools within 24 hours or two or fewer episodes of loose stools accompanied by one or more episodes of vomiting. Vomitus and stool samples from affected passengers were tested for norovirus by reverse transcriptase-polymerase chain reaction. Environmental health officers performed an environmental investigation following VSP protocol. Questionnaires about food items consumed and behavioral risk factors were placed in cabin mailboxes (n = 2,018). A case-control study design using multivariable logistic regression tested associations between risk factors and disease. A total of 359 passengers (24.1% of respondents) met the case definition. Four of seven clinical specimens tested positive for norovirus. No significant deficiencies in environmental health practices were identified, and no meal servings were associated with disease. Having a cabin mate sick with diarrhea or vomiting [odds ratio (OR): 3.40; 95% confidence interval (CI) = 1.80-6.44] and using a specific women's toilet that was contaminated with vomit (OR: 5.13; 95% CI = 1.40-18.78) were associated with disease. Washing hands before meals was protective (OR: 0.25; 95% CI = 0.12-0.54) against disease. Widespread person-to-person norovirus outbreaks can occur on board cruise ships, even with appropriate environmental health practices. Programs to prevent and control norovirus outbreaks on board cruise ships should involve strategies that disrupt person-to-person spread and emphasize hand washing.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

PubMed

Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2009-08-01

To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

Risk factors for Kaposi's sarcoma in human immunodeficiency virus patients after initiation of antiretroviral therapy: A nested case-control study in Kenya.

PubMed

Lupia, Rodgers; Wabuyia, Peter B; Otiato, Peter; Fang, Chi-Tai; Tsai, Feng-Jen

2017-12-01

This study aimed to evaluate the association between highly active antiretroviral therapy (HAART) adherence and development of Kaposi's sarcoma (KS) in human immunodeficiency virus (HIV)/AIDS patients. We conducted a retrospective nested case-control study of 165 participants (33 cases and 132 controls) receiving HAART care at Maseno Hospital, Kenya, from January 2005 to October 2013. Cases were HIV-positive adults with KS, who were matched with controls in a ratio of 1:4 based on age (±5 years of each case), sex, and KS diagnosis date. Perfect adherence to HAART was assessed on every clinic visit by patients' self-reporting and pill counts. Chi-square tests were performed to compare socioeconomic and clinical statuses between cases and controls. A conditional logistic regression was used to assess the effects of perfect adherence to HAART, the latest CD4 count, education level, distance to health-care facility, initial World Health Organization stage, and number of regular sexual partners on the development of KS. Only 63.6% participants reported perfect adherence, and the control group had a significantly higher percentage of perfect adherence (75.0%) than did cases (18.2%). After adjustment for potential imbalances in the baseline and clinical characteristics, patients with imperfect HAART adherence had 20-times greater risk of developing KS than patients with perfect HAART adherence [hazard ratios: 21.0, 95% confidence interval: 4.2-105.1]. Patients with low latest CD4 count (≤350 cells/mm 3 ) had a seven-times greater risk of developing KS than did their counterparts (HRs: 7.1, 95% CI: 1.4-36.2). Imperfect HAART adherence and low latest CD4 count are significantly associated with KS development. Copyright © 2015. Published by Elsevier B.V.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population.

PubMed

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population*

PubMed Central

Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

2013-01-01

The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)AA+AG: 0.654, 95% confidence interval (CI): 0.406–1.055; P=0.082), rs4233532 (ORCC: 1.667, 95% CI: 0.967–2.876; ORCT: 1.435, 95% CI: 0.998–2.063; P=0.077), and rs2881930 (ORCC: 0.263, 95% CI: 0.095–0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (ORAA+AG: 1.233, 95% CI: 0.903–1.683), rs4233532 (ORCC: 0.892, 95% CI: 0.640–1.243; ORCT: 1.134, 95% CI: 0.897–1.433), and rs2881930 (ORCC: 1.096, 95% CI: 0.620–1.938; ORCT: 1.009, 95% CI: 0.801–1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319–2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC. PMID:23303631

4-aminobutyrate aminotransferase (ABAT): genetic and pharmacological evidence for an involvement in gastro esophageal reflux disease.

PubMed

Jirholt, Johan; Asling, Bengt; Hammond, Paul; Davidson, Geoffrey; Knutsson, Mikael; Walentinsson, Anna; Jensen, Jörgen M; Lehmann, Anders; Agreus, Lars; Lagerström-Fermer, Maria

2011-04-28

Gastro-esophageal reflux disease (GERD) is partly caused by genetic factors. The underlying susceptibility genes are currently unknown, with the exception of COL3A1. We used three independent GERD patient cohorts to identify GERD susceptibility genes. Thirty-six families, demonstrating dominant transmission of GERD were subjected to whole genome microsatellite genotyping and linkage analysis. Five linked regions were identified. Two families shared a linked region (LOD 3.9 and 2.0) on chromosome 16. We used two additional independent GERD patient cohorts, one consisting of 219 trios (affected child with parents) and the other an adult GERD case control cohort consisting of 256 cases and 485 controls, to validate individual genes in the linked region through association analysis. Sixty six single nucleotide polymorphism (SNP) markers distributed over the nine genes present in the linked region were genotyped in the independent GERD trio cohort. Transmission disequilibrium test analysis followed by multiple testing adjustments revealed a significant genetic association for one SNP located in an intron of the gene 4-aminobutyrate aminotransferase (ABAT) (P(adj) = 0.027). This association did not replicate in the adult case-control cohort, possibly due to the differences in ethnicity between the cohorts. Finally, using the selective ABAT inhibitor vigabatrin (γ-vinyl GABA) in a dog study, we were able to show a reduction of transient lower esophageal sphincter relaxations (TLESRs) by 57.3 ± 11.4 % (p = 0.007) and the reflux events from 3.1 ± 0.4 to 0.8 ± 0.4 (p = 0.007). Our results demonstrate the direct involvement of ABAT in pathways affecting lower esophageal sphincter (LES) control and identifies ABAT as a genetic risk factor for GERD.

Are Weight Status and Cognition Associated? An Examination of Cognitive Development in Children and Adolescents with Anorexia Nervosa 1 Year after First Hospitalisation.

PubMed

Kjaersdam Telléus, Gry; Fagerlund, Birgitte; Jepsen, Jens Richardt; Bentz, Mette; Christiansen, Eva; Valentin, Jan Brink; Thomsen, Per Hove

2016-09-01

The aim of this study was to characterise the association between the cognitive profile and weight restoration in children and adolescents with anorexia nervosa. The study was a longitudinal, matched case-control, multicentre study. An assessment of cognitive functions was conducted by using the Wechsler Intelligence Scale for Children-III/the Wechsler Adult Intelligence Scale-III, the Test of Memory and Learning-second edition, Trail Making Tests A and B, the Rey-Osterrieth Complex Figure Test and the Cambridge Neuropsychological Test Automated Battery. One hundred twenty individuals, 60 patients with anorexia nervosa with mean age of 14.65 (SD 1.820) years and 60 healthy controls with mean age of 14.76 (SD 1.704) years, participated. No association was found between weight recovery and cognitive functions. However, a significant increase in motor speed was found in Trail Making Test A (p = 0.004), Reaction Time (RTI) five-choice movement time (p = 0.002) and RTI simple movement time (p = 0.011), resulting in a normalisation corresponding to that found in healthy controls. Furthermore, a significantly lower score in the perceptual organization index (p = 0.029) was found at follow-up. Weight recovery appears not to be associated with cognition. Copyright © 2016 The Authors European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd. Copyright © 2016 The Authors European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.

Genetic association between BDNF gene polymorphisms and phobic disorders: a case-control study among mainland Han Chinese.

PubMed

Xie, Bing; Wang, Binbin; Suo, Peisu; Kou, Changgui; Wang, Jing; Meng, Xiangfei; Cheng, Longfei; Ma, Xu; Yu, Yaqin

2011-07-01

Phobic disorders are a common group of syndromes comprising persistently recurring, irrational severe anxiety of specific objects, activities, or situations with avoidance behavior of the phobic stimulus. The present study investigated the association between whole region polymorphisms, (including the Val66Met variant), in the BDNF gene and phobic disorders among Han Chinese young adults. We conducted a case-control study to investigate the genetic association between BDNF polymorphisms and phobic disorders among mainland Chinese. One hundred and twenty young adults with phobic disorders and 267 matched controls were recruited. Three tag SNPs of BDNF were successfully genotyped by using PCR-based ligase detection reaction (PCR-LDR). We found significant differences in allele distributions of SNP rs10835210 (P<0.001) between the experimental and the control groups. In the haplotype analysis based on linkage-disequilibrium across this gene locus, we demonstrated significant association between phobic disorders and BDNF haplotype CAC (P=0.004). Association was significant after 10(4) permutation tests (P<0.001). To the best of our knowledge, this is the first study showing that the BDNF gene may play a significant role in the etiology of phobic disorders in the Han Chinese population. Copyright © 2010. Published by Elsevier B.V.

Association between androgenetic alopecia and coronary artery disease in young male patients.

PubMed

Sharma, Kamal H; Jindal, Anchal

2014-01-01

Several studies have demonstrated an association between androgenetic alopecia (AGA) and cardiovascular disease. Still controversies exist regarding the association. Are they truly associated? The purpose of the present study was to assess the prevalence of AGA and establish its association in young (<45 years) Asian Indian Gujarati male patients having coronary artery disease (CAD). Case-control prospective multicentric study was carried out on 424 men. Case group consisted of 212 male subjects having CAD (Group 1) and another 212, either sibling or first degree male relative of the case subjects (having no evidence of CAD) were considered as the control group (Group 2). Age, total cholesterol, incidence of diabetes mellitus, and hypertension were similar in both groups. The degree of alopecia was assessed using the Norwood-Hamilton scale for men. Statistical analysis was performed using Chi-square test. AGA was found in 80 (37.73%) young CAD patients (Group 1), whereas 44 (20.7%) of patients had alopecia in the control group (Group 2). There was statistically significant association between male AGA and CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 ± 4.26). Statistically significant association was found between high grade baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95% CI, 1.108 ± 5.033). There is statistically significant association of AGA in young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient is 37.73%. This study implies early onset AGA in male is independently associated with CAD, though mechanisms need to be investigated.

Cancer Screening: How Do Screening Tests Become Standard Tests?

MedlinePlus

... more groups. The people in one group (the control group ) may be given a standard screening test (if one exists) or no screening test. The ... for the human papillomavirus (HPV) and those who test negative for HPV. The ... Case-control studies Case-control studies are like cohort studies ...

Active case finding for carbapenemase-producing Enterobacteriaceae in a teaching hospital: prevalence and risk factors for colonization.

PubMed

Poole, K; George, R; Decraene, V; Shankar, K; Cawthorne, J; Savage, N; Welfare, W; Dodgson, A

2016-10-01

Over the past decade, the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) has increased. Whilst basic infection prevention and control practices reduce the risk of transmission, cases of unrecognized carriage pose a potential risk of transmission. To estimate the prevalence of CPE and explore risk factors associated with colonization within a large teaching hospital with an established CPE outbreak. All inpatients that had not previously tested positive for CPE were offered testing. Demographic and hospital episode data were also collected, together with antibiotic and proton pump inhibitor (PPI) use in the preceding 24h. This study identified 70 CPE-positive cases (26 newly identified and 44 previously known) and 592 CPE-negative cases, giving a combined prevalence of 11% [95% confidence interval (CI) 8-13]. Medication (antibiotic and PPI use), previous admission, ethnicity and length of stay were assessed as risk factors for colonization, and none were found to be independently associated with CPE colonization. Using logistic regression, age [odds ratio (OR) 1.03, 95% CI 1.01-1.07] and antibiotic use (OR 2.55, 95% CI 1.08-6.03) were the only risk factors significantly associated with CPE colonization. This study has added to the evidence base by estimating the prevalence of CPE among inpatients in an acute hospital with an established CPE outbreak. A case-finding exercise was feasible and identified a number of new cases. Despite a small sample size, increasing age and prescription of an antibiotic on the day of testing were significantly associated with CPE colonization. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

PubMed

Amir, Eitan; Cecchini, Reena S; Ganz, Patricia A; Costantino, Joseph P; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J

2012-06-01

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit.

Is selective mutism associated with deficits in memory span and visual memory?: An exploratory case-control study.

PubMed

Kristensen, Hanne; Oerbeck, Beate

2006-01-01

Our main aim in this study was to explore the association between selective mutism (SM) and aspects of nonverbal cognition such as visual memory span and visual memory. Auditory-verbal memory span was also examined. The etiology of SM is unclear, and it probably represents a heterogeneous condition. SM is associated with language impairment, but nonspecific neurodevelopmental factors, including motor problems, are also reported in SM without language impairment. Furthermore, SM is described in Asperger's syndrome. Studies on nonverbal cognition in SM thus merit further investigation. Neuropsychological tests were administered to a clinical sample of 32 children and adolescents with SM (ages 6-17 years, 14 boys and 18 girls) and 62 nonreferred controls matched for age, gender, and socioeconomic status. We used independent t-tests to compare groups with regard to auditory-verbal memory span, visual memory span, and visual memory (Benton Visual Retention Test), and employed linear regression analysis to study the impact of SM on visual memory, controlling for IQ and measures of language and motor function. The SM group differed from controls on auditory-verbal memory span but not on visual memory span. Controlled for IQ, language, and motor function, the SM group did not differ from controls on visual memory. Motor function was the strongest predictor of visual memory performance. SM does not appear to be associated with deficits in visual memory span or visual memory. The reduced auditory-verbal memory span supports the association between SM and language impairment. More comprehensive neuropsychological studies are needed.

Common genetic variants associated with disease from genome-wide association studies are mutually exclusive in prostate cancer and rheumatoid arthritis.

PubMed

Orozco, Gisela; Goh, Chee L; Al Olama, Ali Amin; Benlloch-Garcia, Sara; Govindasami, Koveela; Guy, Michelle; Muir, Kenneth R; Giles, Graham G; Severi, Gianluca; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Kote-Jarai, Zsofia; Easton, Douglas F; Eyre, Steve; Eeles, Rosalind A

2013-06-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10(-4) ; odds ratio [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. However, further analyses showed that the association of this allele was due to confounding by RA-associated HLA-DRB1 alleles. There is currently no evidence that SNPs associated with PrCa at genome-wide significance are associated with the development of RA. Studies like this are important in determining if common genetic risk profiles might predispose individuals to many diseases, which could have implications for public health in terms of screening and chemoprevention. © 2012 BJU International.

A Case-control Study on the Relationship between Mycoplasma genitalium Infection in Women with Normal Pregnancy and Spontaneous Abortion using Polymerase Chain Reaction.

PubMed

Ramazanzadeh, Rashid; Khodabandehloo, Mazaher; Farhadifar, Fariba; Rouhi, Samaneh; Ahmadi, Amjad; Menbari, Shaho; Fallahi, Fariba; Mirnejad, Reza

2016-10-01

Mycoplasma genitalium infections are suggested as causes of a number of pathological outcomes in pregnant women. The aim of this study was to evaluate the frequency of M. genitalium infections among pregnant women and its association with spontaneous abortion. In this case-control study we included 109 women with spontaneous abortion with a gestational age of 10-20 weeks (patients), and 109 women with normal pregnancy with a gestational age of 20-37 weeks (controls) in Sanandaj, Iran. Using specific primers and extracted DNA from endocervical swabs, a polymerase chain reaction was conducted for the detection of M. genitalium infection in both groups. The frequency of M. genitalium infection in patient and control groups was one (0.91%) and three (2.75%), respectively. In both control and patient groups using Fisher test, no association between mycoplasma infection and spontaneous abortion was seen. M. genitalium may be positive in the genital tract of some pregnant women but was not associated with spontaneous abortion. Further powerful studies with larger sample sizes are needed for the determination of a possible role of M. genitalium in pregnancy outcomes and spontaneous abortion.

Maternal asthma and idiopathic preterm labor.

PubMed

Kramer, M S; Coates, A L; Michoud, M C; Dagenais, S; Moshonas, D; Davis, G M; Hamilton, E F; Nuwayhid, B; Joshi, A K; Papageorgiou, A

1995-11-15

Previous studies suggest that women with asthma are at increased risk of preterm birth. Moreover, drugs (especially beta-agonists) used to treat asthma are also used to treat preterm labor. The authors carried out a case-control study of 555 women from three hospital centers with idiopathic preterm labor (< 37 weeks), including two overlapping (i.e., non-mutually exclusive) subsamples: cases with early idiopathic preterm labor (< 34 weeks) and cases with idiopathic recurrent preterm labor (< 37 weeks plus a previous history of preterm delivery or second-trimester miscarriage). Controls were matched to cases according to race and smoking history prior to and during pregnancy. All subjects responded in person to questions about atopic, respiratory, obstetric, and sociodemographic histories. Subjects in the early and recurrent preterm labor subsamples were also asked to undergo spirometric testing with methacholine challenge 6-12 weeks after delivery. Cases were significantly more likely to report histories of asthma symptoms and physician-diagnosed asthma (matched odds ratios of 2-3) than controls, particularly those cases with recurrent preterm labor. No significant associations were observed, however, with methacholine responsiveness. These results could not be explained by residual confounding by smoking or other variables, nor by selective recall of asthma symptoms and histories by cases. Women with asthma are at increased risk of idiopathic preterm labor. The fact that no such association was seen with methacholine responsiveness suggests that nonatopic, noncholinergic mechanisms may link bronchial and uterine smooth muscle lability.

Association Between Baseline Blood Pressures, Heart Rates, and Vasovagal Syncope in Children and Adolescents.

PubMed

Adlakha, Himanshu; Gupta, Ruchi; Hassan, Romana; Kern, Jeffrey H

2018-01-28

Vasovagal syncope is the most common cause of syncope in children and adults, accounting for 50-66% of unexplained syncope. There are no studies establishing the relationship between syncope, baseline heart rate, and blood pressure. To identify a possible association between baseline blood pressure and heart rate with syncope. We conducted a questionnaire-based chart review study. A questionnaire was distributed to the guardian of children between eight and 18 years of age who attended the Pediatric Ambulatory Care Clinic at Flushing Hospital Medical Center. Based on the responses in the questionnaire, subjects were classified either as cases (positive for syncope) or controls (negative for syncope). Children and adolescents with neurological, cardiac, or any medical condition that can cause syncopal episodes were excluded from the study. Data collected from the questionnaire included age, gender, ethnicity, medical history, family history of syncope, and the amount of salt used in food. Anthropometric and vital signs for the current visit (height, weight, BMI, blood pressure, and heart rate) and vital signs from two previous visits were collected from electronic medical records. The data was analyzed using t-test and chi-square test with Microsoft Excel software (Microsoft Office Standard, v. 14, Microsoft; 2010); p<0.05 was considered significant. A total of 197 subjects were included in this study. There were 18 cases and 179 controls. Of the cases, (4/18) 22.2% were more likely to have a systolic blood pressure lower than the 10th percentile for their gender, age, and height as compared with controls (7/179) 3.9%, p = 0.003. The subjects with a history of syncope were more likely to add salt to their food (p = 0.004). There were no significant differences between cases and controls for age, gender, ethnicity between cases and controls for systolic blood pressure. No significant difference was observed between the heart rates of cases and controls. Children and adolescents with syncope were more likely to have a systolic blood pressure lower than the 10th percentile, and there was no difference in the baseline heart rate. In addition, children with syncope were more likely to add salt to their food.

Skin test reactivity to female sex hormones in women with primary unexplained recurrent pregnancy loss.

PubMed

Ellaithy, Mohamed I; Fathi, Hesham M; Farres, Mohamed N; Taha, Marwa S

2013-09-01

The objective was to examine the hypothesis that primary unexplained recurrent pregnancy loss might be associated with an inappropriate immunologically mediated response to progesterone and/or estrogen. This prospective study included 47 women with two or more documented consecutive early pregnancy losses of unknown etiology, and no previous history of deliveries. Intradermal skin testing was performed in the luteal phase of the cycle (days 16-20) using estradiol benzoate, progesterone, and a placebo of refined sesame oil. Immediate (20 min) and late (24h and 1 week) skin test readings for all cases were compared with those of 12 parous women of comparable age with no history of spontaneous miscarriages, premenstrual disorders, pregnancy, or sex hormone-related allergic or autoimmune diseases. Main outcome measure was skin test reactivity to estradiol and/or progesterone. Immediate skin test reactivity to both hormones was observed among half of the cases at 20 min. A papule after 24h, which persisted for up to 1 week, was observed among 32 (68.1%) and 34 (72.3%) cases at the sites of estrogen and progesterone injection, respectively. 55.3% of cases had combined skin test reactivity to both estradiol and progesterone at 1 week. All women in the control group showed absence of skin test reactivity for both estradiol and progesterone at 20 min, 24h, and 1 week. None of the subjects in either group showed skin test reactivity to placebo. There is an association between primary unexplained recurrent pregnancy loss and skin test reactivity to female sex hormones. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Vehicle exhaust exposure in an incident case-control study of adult asthma.

PubMed

Modig, L; Järvholm, B; Rönnmark, E; Nyström, L; Lundbäck, B; Andersson, C; Forsberg, B

2006-07-01

The objective of this case-control study was to evaluate whether traffic-related air pollution exposure at home increases the risk of asthma in adults and to compare two commonly used exposure variables and differences between urban and rural living. Incident cases of asthma and matched controls of subjects aged 20-60 yrs were recruited in Luleå, Sweden. In total 203 cases and 203 controls were enrolled in the study. Exposure was estimated by traffic flow and measured levels of outdoor nitrogen dioxide (NO2) in the surrounding environment of each home, respectively. The relationship between measured levels of NO2 and traffic flow was studied using linear regression. The results indicated a nonsignificant tendency between living in a home close to a high traffic flow and an increased risk of asthma. The association between asthma and measured NO2 was weak and not significant, but the skin-prick test result acted as an effect modifier with a borderline significant association among positives. The correlation between traffic flow and outdoor NO2 was low. The results suggest that living close to high traffic flows might increase the asthma incidence in adults, while the tendency for nitrogen dioxide was only seen among atopics. Traffic flow and nitrogen dioxide had a lower than expected correlation.

Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality

PubMed Central

Cushman, Laura A.; Stein, Karen; Duffy, Charles J.

2008-01-01

Background: Older adults get lost, in many cases because of recognized or incipient Alzheimer disease (AD). In either case, getting lost can be a threat to individual and public safety, as well as to personal autonomy and quality of life. Here we compare our previously described real-world navigation test with a virtual reality (VR) version simulating the same navigational environment. Methods: Quantifying real-world navigational performance is difficult and time-consuming. VR testing is a promising alternative, but it has not been compared with closely corresponding real-world testing in aging and AD. We have studied navigation using both real-world and virtual environments in the same subjects: young normal controls (YNCs, n = 35), older normal controls (ONCs, n = 26), patients with mild cognitive impairment (MCI, n = 12), and patients with early AD (EAD, n = 14). Results: We found close correlations between real-world and virtual navigational deficits that increased across groups from YNC to ONC, to MCI, and to EAD. Analyses of subtest performance showed similar profiles of impairment in real-world and virtual testing in all four subject groups. The ONC, MCI, and EAD subjects all showed greatest difficulty in self-orientation and scene localization tests. MCI and EAD patients also showed impaired verbal recall about both test environments. Conclusions: Virtual environment testing provides a valid assessment of navigational skills. Aging and Alzheimer disease (AD) share the same patterns of difficulty in associating visual scenes and locations, which is complicated in AD by the accompanying loss of verbally mediated navigational capacities. We conclude that virtual navigation testing reveals deficits in aging and AD that are associated with potentially grave risks to our patients and the community. GLOSSARY AD = Alzheimer disease; EAD = early Alzheimer disease; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; ONC = older normal control; std. wt. = standardized weight; THSD = Tukey honestly significant difference; VR = virtual reality; YNC = young normal control. PMID:18794491

Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate-cancer associated SNPs for familial disease

PubMed Central

Teerlink, Craig C.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Foulkes, William D.; Giles, Graham G.; Hopper, John L.; Severi, Gianluca; Eeles, Ros; Easton, Douglas; Kote-Jarai, Zsofia; Guy, Michelle; Cooney, Kathleen A.; Ray, Anna M.; Zuhlke, Kimberly A.; Lange, Ethan M.; FitzGerald, Liesel M.; Stanford, Janet L.; Ostrander, Elaine A.; Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Carpten, John; Bailey-Wilson, Joan; Whittemore, Alice S.; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Catalona, William J.; Zheng, S. Lilly; Jin, Guangfu; Lu, Lingyi; Xu, Jianfeng; Camp, Nicola J.; Cannon-Albright, Lisa A.

2013-01-01

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p≤1E−3) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may be contribute risk to aggressive disease. PMID:24162621

Disciplinary action by medical boards and prior behavior in medical school.

PubMed

Papadakis, Maxine A; Teherani, Arianne; Banach, Mary A; Knettler, Timothy R; Rattner, Susan L; Stern, David T; Veloski, J Jon; Hodgson, Carol S

2005-12-22

Evidence supporting professionalism as a critical measure of competence in medical education is limited. In this case-control study, we investigated the association of disciplinary action against practicing physicians with prior unprofessional behavior in medical school. We also examined the specific types of behavior that are most predictive of disciplinary action against practicing physicians with unprofessional behavior in medical school. The study included 235 graduates of three medical schools who were disciplined by one of 40 state medical boards between 1990 and 2003 (case physicians). The 469 control physicians were matched with the case physicians according to medical school and graduation year. Predictor variables from medical school included the presence or absence of narratives describing unprofessional behavior, grades, standardized-test scores, and demographic characteristics. Narratives were assigned an overall rating for unprofessional behavior. Those that met the threshold for unprofessional behavior were further classified among eight types of behavior and assigned a severity rating (moderate to severe). Disciplinary action by a medical board was strongly associated with prior unprofessional behavior in medical school (odds ratio, 3.0; 95 percent confidence interval, 1.9 to 4.8), for a population attributable risk of disciplinary action of 26 percent. The types of unprofessional behavior most strongly linked with disciplinary action were severe irresponsibility (odds ratio, 8.5; 95 percent confidence interval, 1.8 to 40.1) and severely diminished capacity for self-improvement (odds ratio, 3.1; 95 percent confidence interval, 1.2 to 8.2). Disciplinary action by a medical board was also associated with low scores on the Medical College Admission Test and poor grades in the first two years of medical school (1 percent and 7 percent population attributable risk, respectively), but the association with these variables was less strong than that with unprofessional behavior. In this case-control study, disciplinary action among practicing physicians by medical boards was strongly associated with unprofessional behavior in medical school. Students with the strongest association were those who were described as irresponsible or as having diminished ability to improve their behavior. Professionalism should have a central role in medical academics and throughout one's medical career. Copyright 2005 Massachusetts Medical Society.

Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

PubMed Central

Earp, Madalene A.; Kelemen, Linda E.; Magliocco, Anthony M.; Swenerton, Kenneth D.; Chenevix–Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A.; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.; Runnebaum, Ingo B.; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Butzow, Ralf; Bunker, Clareann H.; Modugno, Francesmary; Edwards, Robert P.; Ness, Roberta B.; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K.; Høgdall, Claus K.; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Levine, Douglas A.; Bisogna, Maria; Schildkraut, Joellen M.; Iversen, Edwin S.; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Chandran, Urmila; Orlow, Irene; Olson, Sara H.; Wik, Elisabeth; Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.; van Altena, Anne M.; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Pejovic, Tanja; Bean, Yukie T.; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia–Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F.; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.; Eccles, Diana; Campbell, Ian G.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.; Flanagan, James M.; Paul, James; Brown, Robert; Phelan, Catherine M.; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S.; Le, Nhu D.; Brooks–Wilson, Angela

2014-01-01

Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS (56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low malignant potential (LMP) serous, and 24 for invasive serous EOC), selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95% confidence intervals are reported. Nine variants tagging 6 loci were associated with subtype-specific EOC risk at P<0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR=1.17, P=0.029, n=1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P=0.014, n=2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR=0.86, P=0.0043, n=892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR=0.84, P=0.0007) and LMP serous EOC risk remained statistically significant at P<0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

Analysis of binary responses with outcome-specific misclassification probability in genome-wide association studies.

PubMed

Rekaya, Romdhane; Smith, Shannon; Hay, El Hamidi; Farhat, Nourhene; Aggrey, Samuel E

2016-01-01

Errors in the binary status of some response traits are frequent in human, animal, and plant applications. These error rates tend to differ between cases and controls because diagnostic and screening tests have different sensitivity and specificity. This increases the inaccuracies of classifying individuals into correct groups, giving rise to both false-positive and false-negative cases. The analysis of these noisy binary responses due to misclassification will undoubtedly reduce the statistical power of genome-wide association studies (GWAS). A threshold model that accommodates varying diagnostic errors between cases and controls was investigated. A simulation study was carried out where several binary data sets (case-control) were generated with varying effects for the most influential single nucleotide polymorphisms (SNPs) and different diagnostic error rate for cases and controls. Each simulated data set consisted of 2000 individuals. Ignoring misclassification resulted in biased estimates of true influential SNP effects and inflated estimates for true noninfluential markers. A substantial reduction in bias and increase in accuracy ranging from 12% to 32% was observed when the misclassification procedure was invoked. In fact, the majority of influential SNPs that were not identified using the noisy data were captured using the proposed method. Additionally, truly misclassified binary records were identified with high probability using the proposed method. The superiority of the proposed method was maintained across different simulation parameters (misclassification rates and odds ratios) attesting to its robustness.

Risk factors for acute toxoplasmosis in England and Wales.

PubMed

Said, B; Halsby, K D; O'Connor, C M; Francis, J; Hewitt, K; Verlander, N Q; Guy, E; Morgan, D

2017-01-01

Over 300 cases of acute toxoplasmosis are confirmed by reference testing in England and Wales annually. We conducted a case-control study to identify risk factors for Toxoplasma gondii infection to inform prevention strategies. Twenty-eight cases and 27 seronegative controls participated. We compared their food history and environmental exposures using logistic regression to calculate odds ratios (OR) and 95% confidence intervals in a model controlling for age and sex. Univariable analysis showed that the odds of eating beef (OR 10·7, P < 0·001), poultry (OR 6·4, P = 0·01) or lamb/mutton (OR 4·9, P = 0·01) was higher for cases than controls. After adjustment for potential confounders a strong association between beef and infection remained (OR 5·6, P = 0·01). The small sample size was a significant limitation and larger studies are needed to fully investigate potential risk factors. The study findings emphasize the need to ensure food is thoroughly cooked and handled hygienically, especially for those in vulnerable groups.

Use of acetaminophen and risk of endometrial cancer: evidence from observational studies.

PubMed

Ding, Yuan-Yuan; Yao, Peng; Verma, Surya; Han, Zhen-Kai; Hong, Tao; Zhu, Yong-Qiang; Li, Hong-Xi

2017-05-23

Previous meta-analyses suggested that aspirin was associated with reduced risk of endometrial cancer. However, there has been no study comprehensively summarize the evidence of acetaminophen use and risk of endometrial cancer from observational studies. We systematically searched electronic databases (PubMed , EMBASE, Web of Science, and Cochrane Library) for relevant cohort or case-control studies up to February 28, 2017. Two independent authors performed the eligibility evaluation and data extraction. All differences were resolved by discussion. A random-effects model was applied to estimate summary relative risks (RRs) with 95% CIs. All statistical tests were two-sided. Seven observational studies including four prospective cohort studies and three case-control studies with 3874 endometrial cancer cases were included for final analysis. Compared with never use acetaminophen, ever use this drug was not associated with risk of endometrial cancer (summarized RR = 1.02; 95% CI: 0.93-1.13, I2 = 0%). Similar null association was also observed when compared the highest category of frequency/duration with never use acetaminophen (summarized RR = 0.88; 95% CI: 0.70-1.11, I2 = 15.2%). Additionally, the finding was robust in the subgroup analyses stratified by study characteristics and adjustment for potential confounders and risk factors. There was no evidence of publication bias by a visual inspection of a funnel plot and formal statistical tests. In summary, the present meta-analysis reveals no association between acetaminophen use and risk of endometrial cancer. More large scale prospective cohort studies are warranted to confirm our findings and carry out the dose-response analysis of aforementioned association.

Opioid system genes in alcoholism: a case-control study in Croatian population.

PubMed

Cupic, B; Stefulj, J; Zapletal, E; Matosic, A; Bordukalo-Niksic, T; Cicin-Sain, L; Gabrilovac, J

2013-10-01

Due to their involvement in dependence pathways, opioid system genes represent strong candidates for association studies investigating alcoholism. In this study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins, were analyzed in a case-control study that included 354 male alcohol-dependent and 357 male control subjects from Croatian population. Analysis of allele and genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN revealed no differences between the tested groups. The same was true when alcohol-dependent persons were subdivided according to the Cloninger's criteria into type-1 and type-2 groups, known to differ in the extent of genetic control. Thus, the data obtained suggest no association of the selected polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian population. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.

PubMed

Elmore, James R; Obmann, Melissa A; Kuivaniemi, Helena; Tromp, Gerard; Gerhard, Glenn S; Franklin, David P; Boddy, Amy M; Carey, David J

2009-06-01

The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (AAAs). A genome wide association study was carried out using pooled DNA samples from 123 AAA cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with AAA was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. A genome wide association study of AAA cases and controls identified a candidate AAA-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with AAA in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with AAA was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for AAA. The AAA-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. This study identifies a region on chromosome 3 that is significantly associated with AAA in 2 distinct study populations.

The association between HLA DQ genetic polymorphism and type 1 diabetes in a case-parent study conducted in an admixed population.

PubMed

Mimbacas, Adriana; Pérez-Bravo, Fernando; Santos, Jose Luis; Pisciottano, Carmen; Grignola, Rosario; Javiel, Gerardo; Jorge, Ana Maria; Cardoso, Horacio

2004-01-01

Susceptibility to the type 1 diabetes is genetically controlled and there is an increased risk associated with the presence of some specific alleles of the human leukocyte antigens class II loci (DQA1 and DQB1 genes). The purpose of this study is to evaluate the association between type 1 diabetes and HLA DQ alleles using case-parents trios in the admixed population of Uruguay composed by a mixture of Caucasian, Amerindian and Negroid populations. DQA1 and DQB1 genotyping was performed by polimerase chain reaction followed by oligospecific probes hybridization in 51 case-parents trios. The transmission disequilibrium test was used for detecting differential transmission in the HLA DQ loci. DQB1*0302 was the only allele for which preferential transmission is suggested (probability of transmission = 67.56%; exact p-value TDT = 0.047 uncorrected for multiple comparisons). DQA1*0301 allele showed a trend for preferential transmission without achieving statistical significance. This result would confirm the hypothesis previously advanced in a case-control study. Therefore, DQB1*0302 allele could be considered as the most important susceptibility allele for developing type 1 diabetes in Uruguay population.

A genome-wide association study of breast cancer in women of African ancestry

PubMed Central

Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Millikan, Robert C.; Ambrosone, Christine B.; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Palmer, Julie R.; Hu, Jennifer J.; Rebbeck, Tim R.; Ziegler, Regina G.; Nyante, Sarah; Bandera, Elisa V.; Ingles, Sue A.; Press, Michael F.; Ruiz-Narvaez, Edward A.; Deming, Sandra L.; Rodriguez-Gil, Jorge L.; DeMichele, Angela; Chanock, Stephen J.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong; Huo, Dezheng; Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Simon, Michael S.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Le Marchand, Loic; Kolonel, Laurence N.; Henderson, Brian E.; Haiman, Christopher A.

2013-01-01

Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10−6 and 10−5 in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3×10−6; rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5×10−5). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. PMID:22923054

Genetic Association Study of KCNQ5 Polymorphisms with High Myopia.

PubMed

Liao, Xuan; Yap, Maurice K H; Leung, Kim Hung; Kao, Patrick Y P; Liu, Long Qian; Yip, Shea Ping

2017-01-01

Identification of genetic variations related to high myopia may advance our knowledge of the etiopathogenesis of refractive error. This study investigated the role of potassium channel gene (KCNQ5) polymorphisms in high myopia. We performed a case-control study of 1563 unrelated Han Chinese subjects (809 cases of high myopia and 754 emmetropic controls). Five tag single-nucleotide polymorphisms (SNPs) of KCNQ5 were genotyped, and association testing with high myopia was conducted using logistic regression analysis adjusted for sex and age to give P asym values, and multiple comparisons were corrected by permutation test to give P emp values. All five noncoding SNPs were associated with high myopia. The SNP rs7744813, previously shown to be associated with refractive error and myopia in two GWAS, showed an odds ratio of 0.75 (95% CI 0.63-0.90; P emp = 0.0058) for the minor allele. The top SNP rs9342979 showed an odds ratio of 0.75 (95% CI 0.64-0.89; P emp = 0.0045) for the minor allele. Both SNPs are located within enhancer histone marks and DNase-hypersensitive sites. Our data support the involvement of KCNQ5 gene polymorphisms in the genetic susceptibility to high myopia and further exploration of KCNQ5 as a risk factor for high myopia.

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

PubMed

Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

2014-06-01

One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 × 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects. The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments.

Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study.

PubMed

Jørgenrud, Benedicte; Stene, Lars C; Tapia, German; Bøås, Håkon; Pepaj, Milaim; Berg, Jens P; Thorsby, Per M; Orešič, Matej; Hyötyläinen, Tuulia; Rønningen, Kjersti S

2017-03-01

The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes. Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites. Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age. Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Helicobacter pylori coinfection is a confounder, modulating mucosal inflammation in oral submucous fibrosis.

PubMed

Rajendran, R; Rajeev, R; Anil, S; Alasqah, Mohammed; Rabi, Abdul Gafoor

2009-01-01

The oral cavity has been considered a potential reservoir for Helicobacter pylori (H pylori) , from where the organism causes recurrent gastric infections. With this case-control study we tried to evaluate the role of H pylori in the etiology of mucosal inflammation, a condition that compounds the morbid state associated with oral submucous fibrosis (OSF). Subjects ( n = 150) were selected following institutional regulations on sample collection and grouped into test cases and positive and negative controls based on the presence of mucosal fibrosis and inflammation. The negative controls had none of the clinical signs. All patients underwent an oral examination as well as tests to assess oral hygiene/periodontal disease status; a rapid urease test (RUT) of plaque samples was also done to estimate the H pylori bacterial load. We used univariate and mutivariate logistic regression for statistical analysis of the data and calculated the odds ratios to assess the risk posed by the different variables. The RUT results differed significantly between the groups, reflecting the variations in the bacterial loads in each category. The test was positive in 52% in the positive controls (where nonspecific inflammation of oral mucosa was seen unassociated with fibrosis), in 46% of the test cases, and in 18% of the negative controls (healthy volunteers) (chi2 = 13.887; P < 0.01). A positive correlation was seen between the oral hygiene/periodontal disease indices and RUT reactivity in all the three groups. The contribution of the H pylori in dental plaque to mucosal inflammation and periodontal disease was significant. Logistic regression analysis showed gastrointestinal disease and poor oral hygiene as being the greatest risk factors for bacterial colonization, irrespective of the subject groups. A positive correlation exists between RUT reactivity and the frequency of mucosal inflammation.

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

PubMed Central

Letra, Ariadne; Fakhouri, Walid; Fonseca, Renata F.; Menezes, Renato; Kempa, Inga; Prasad, Joanne L.; McHenry, Toby G.; Lidral, Andrew C.; Moreno, Lina; Murray, Jeffrey C.; Daack-Hirsch, Sandra; Marazita, Mary L.; Castilla, Eduardo E.; Lace, Baiba; Orioli, Ieda M.; Granjeiro, Jose M.; Schutte, Brian C.; Vieira, Alexandre R.

2012-01-01

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10−6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10−6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10−6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. PMID:23029012

Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease.

PubMed

Robak, Laurie A; Jansen, Iris E; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Jankovic, Joseph; Heutink, Peter; Shulman, Joshua M

2017-12-01

Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses

PubMed Central

Ruszczyk, Melanie; Zirpoli, Gary; Kumar, Shicha; Bandera, Elisa V.; Bovbjerg, Dana H.; Jandorf, Lina; Khoury, Thaer; Hwang, Helena; Ciupak, Gregory; Pawlish, Karen; Schedin, Pepper; Masso-Welch, Patricia; Ambrosone, Christine B.; Hong, Chi-Chen

2015-01-01

Purpose Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS. Methods We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n=650) or pure IDC (n=181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression. Results Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk for pure IDC was lower in women with body mass index (BMI) 25 to <30 kg/m2 (Odds Ratio (OR)=0.66; 95% confidence interval (CI), 0.35-1.23) and BMI≥30 kg/m2 (OR=0.33; 95% CI, 0.18-0.67) compared to women with BMI<25 kg/m2, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR=0.55; 95% CI, 0.32-0.94) or longer (OR=0.47; 95% CI, 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed. Conclusions Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the development patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS. PMID:26621543

Is there an association between flow diverter fish mouthing and delayed-type hypersensitivity to metals?-a case-control study.

PubMed

Kocer, Naci; Mondel, Prabath Kumar; Yamac, Elif; Kavak, Ayse; Kizilkilic, Osman; Islak, Civan

2017-11-01

Flow diverters are increasingly used in the treatment of complex and giant intracranial aneurysms. However, they are associated with complications like late aneurysmal rupture. Additionally, flow diverters show focal structural decrease in luminal diameter without any intimal hyperplasia. This resembles a "fish mouth" when viewed en face. In this pilot study, we tested the hypothesis of a possible association between flow diverter fish-mouthing and delayed-type hypersensitivity to its metal constituents. We retrospectively reviewed patient records from our center between May 2010 and November 2015. A total of nine patients had flow diverter fish mouthing. A control group of 25 patients was selected. All study participants underwent prospective patch test to detect hypersensitivity to flow diverter metal constituents. Analysis was performed using logistic regression analysis and Wilcoxon sign rank sum test. Univariate and multivariate analyses were performed to test variables to predict flow diverter fish mouthing. The association between flow diverter fish mouthing and positive patch test was not statistically significant. In multivariate analysis, history of allergy and maximum aneurysm size category was associated with flow diverter fish mouthing. This was further confirmed on Wilcoxon sign rank sum test. The study showed statistically significant association between flow diverter fish mouthing and history of contact allergy and a small aneurysmal size. Further large-scale studies are needed to detect a statistically significant association between flow diverter fish mouthing and patch test. We recommend early and more frequent follow-up imaging in patients with contact allergy to detect flow diverter fish mouthing and its subsequent evolution.

C allele of the rs2209972 single nucleotide polymorphism of the insulin degrading enzyme gene and Alzheimer's disease in type 2 diabetes, a case control study.

PubMed

Gutiérrez-Hermosillo, Hugo; Díaz De León-González, Enrique; Palacios-Corona, Rebeca; Cedillo-Rodríguez, Javier Armando; Camacho-Luis, Abelardo; Reyes-Romero, Miguel Arturo; Medina-Chávez, Juan Humberto; Blandón, Pedro A

2015-02-20

In the last few decades we have witnessed an interesting transformation of the population pyramids throughout the world. As the population's life expectancy increases, there are more chronic diseases such as diabetes mellitus and dementias, and both of them have shown an association. To determine the association between Alzheimer's disease in diabetic patients and the insulin degrading enzyme in outpatients of a second level Hospital in Monterrey, Mexico. This was a case control study in which we included outpatients from the Geriatrics Clinic of a Hospital in Northeastern Mexico. Cases were patients with a Mini Mental Score Exam (MMSE) below 24 and DSM-IV criteria for Dementia. Controls were patients who had MMSE scores greater than 24. Data from 97 patients were analyzed. Regarding physical examination and the results of laboratory tests, there were no differences between the two groups (p>0.05). A 98% prevalence of the insulin degrading enzyme was documented in the sample studied. We found an association between a homozygous status for the CC genotype and Dementia with an estimated Odds Ratio (OR) of 2.5 (CI 95% 1.6-3.3) on the bivariate test, while, on the multivariate analysis, the OR was estimated 3.3 (CI 95% 1.3-8.2). Evidence shows that cognitive impairment is more frequent among those exposed to the C allele of the rs2209972 SNP of the insulin degrading enzyme gene. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Association study of neuregulin-1 gene polymorphisms in a North Indian schizophrenia sample.

PubMed

Kukshal, Prachi; Bhatia, Triptish; Bhagwat, A M; Gur, Raquel E; Gur, Ruben C; Deshpande, Smita N; Nimgaonkar, Vishwajit L; Thelma, B K

2013-03-01

Neuregulin-1 (NRG1) gene polymorphisms have been proposed as risk factors for several common disorders. Associations with cognitive variation have also been tested. With regard to schizophrenia (SZ) risk, studies of Caucasian ancestry samples indicate associations more consistently than East Asian samples, suggesting heterogeneity. To exploit the differences in linkage disequilibrium (LD) structure across ethnic groups, we conducted a SZ case-control study (that included cognitive evaluations) in a sample from the north Indian population. NRG1 variants (n=35 SNPs, three microsatellite markers) were initially analyzed among cases (DSM IV criteria, n=1007) and controls (n=1019, drawn from two groups) who were drawn from the same geographical region in North India. Nominally significant associations with SZ were next analyzed in relation to neurocognitive measures estimated with a computerized neurocognitive battery in a subset of the sample (n=116 cases, n=170 controls). Three variants and one microsatellite showed allelic association with SZ (rs35753505, rs4733263, rs6994992, and microsatellite 420M9-1395, p≤0.05 uncorrected for multiple comparisons). A six marker haplotype 221121 (rs35753505-rs6994992-rs1354336-rs10093107-rs3924999-rs11780123) showed (p=0.0004) association after Bonferroni corrections. Regression analyses with the neurocognitive measures showed nominal (uncorrected) associations with emotion processing and attention at rs35753505 and rs6994992, respectively. Suggestive associations with SZ and SZ-related neurocognitive measures were detected with two SNPs from the NRG1 promoter region in a north Indian cohort. The functional role of the alleles merits further investigation. Copyright © 2013 Elsevier B.V. All rights reserved.

Nevirapine patch testing in Thai human immunodeficiency virus infected patients with nevirapine drug hypersensitivity.

PubMed

Prasertvit, Piyatida; Chareonyingwattana, Angkana; Wattanakrai, Penpun

2017-12-01

Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505. Patients were classified into two groups: (1) study group of 20 HIV NVP hypersensitivity patients and (2) control group of 15 volunteers without NVP hypersensitivity. Both groups were patch tested with purified and commercialized form of NVP in various vehicles. Two HIV patients with NVP hypersensitivity were patch test positive. All controls tested negative. Three HIV patients were positive for HLA-B*3505 and the two patients with positive patch testing were both HLA-B*3505 positive. NVP patch testing in Thai HIV patients is safe and can be used to help confirm the association between NVP and hypersensitivity skin reactions. NVP patch test results significantly correlated with HLA-B*3505. The sensitivity of HLA-B*3505 for positive patch test was 100%. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

PubMed

Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin A; Yen, Catherine; Parashar, Umesh D

2016-05-01

Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests.

PubMed

Oomen, H A; Schipperijn, A J; Drexhage, H A

1996-08-01

Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence of thyroid function abnormalities in a psychiatric population on admission (as compared to the prevalence in a normal population), and (2) whether such thyroid function abnormalities are associated with the occurrence or development of cognitive and affective disorders. Serum was collected 2-3 weeks after hospitalization in 3 major clinics from 3756 psychiatric patients in 1987-1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same area (n = 1877). The prevalence study was followed by a case-control study involving patients from one clinic that had routinely assigned a DSM-IIIR classification to its patients. Cases were those admissions with thyroid abnormalities and three subgroups of cases were randomly formed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to random controls from the same psychiatric population, viz patients without thyroid abnormalities (n = 83). Comparison was with respect to their psychiatric follow-up diagnosis (the investigator was blinded to the thyroid test results). Prevalence study. The percentage of patients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4-4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) > 4.0 mU/l and 4.1% (134/3316) < 0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects with abnormal TSH, indicating the predominantly subclinical character of the thyroid alteration. In comparison, the healthy area controls over 55 years of age showed the same prevalence of positive TPO-antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l. CASE-CONTROL STUDY: In the case control analysis differences could not be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective disorders which were more prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this association, analyses were also carried out excluding patients with such prior drug use. In these analyses affective disorders were still more prevalent in patients with a low serum TSH (particularly in males, 40% in cases vs 9% in controls, P < 0.05). The most significant association was however between TPO-antibody positivity (and in particular with high titre and/or with TSH > 4.0 mU/l) and a subgroup of the affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases vs 0% in controls, P < 0.001). Though causal relations cannot be determined from this cross-sectional study, this admission survey found early forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs, highly significantly associated with rapid cycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.

A high-density association screen of 155 ion transport genes for involvement with common migraine

PubMed Central

Nyholt, Dale R.; LaForge, K. Steven; Kallela, Mikko; Alakurtti, Kirsi; Anttila, Verneri; Färkkilä, Markus; Hämaläinen, Eija; Kaprio, Jaakko; Kaunisto, Mari A.; Heath, Andrew C.; Montgomery, Grant W.; Göbel, Hartmut; Todt, Unda; Ferrari, Michel D.; Launer, Lenore J.; Frants, Rune R.; Terwindt, Gisela M.; de Vries, Boukje; Verschuren, W.M. Monique; Brand, Jan; Freilinger, Tobias; Pfaffenrath, Volker; Straube, Andreas; Ballinger, Dennis G.; Zhan, Yiping; Daly, Mark J.; Cox, David R.; Dichgans, Martin; van den Maagdenberg, Arn M.J.M.; Kubisch, Christian; Martin, Nicholas G.; Wessman, Maija; Peltonen, Leena; Palotie, Aarno

2008-01-01

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case–control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case–control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out. PMID:18676988

Adrenal insufficiency in patients with stable non-cystic fibrosis bronchiectasis

PubMed Central

Rajagopala, Srinivas; Ramakrishnan, Anantharaman; Bantwal, Ganapathi; Devaraj, Uma; Swamy, Smrita; Ayyar, S V; D’Souza, George

2014-01-01

Background & objectives: Suppressed adrenal responses associated with inhaled steroid use have been reported in patients with bronchiectasis and have been shown to be associated with poor quality of life. This study was undertaken to examine the prevalence of suppressed cortisol responses in stable bronchiectasis and determine their correlation with the use of inhaled corticosteroids, radiologic severity of bronchiectasis and quality of life (QOL) scores. Methods: In this case-control study, cases were patients with bronchiectasis and suppressed cortisol responses and controls were healthy volunteers, and patients with bronchiectasis without suppressed cortisol responses. Symptoms, lung function test values, exercise capacity, HRCT severity scores for bronchiectasis, exacerbations, inhaled corticosteroid use and quality of life scores were compared between patients with and without suppressed cortisol values. Results: Forty consecutive patients with bronchiectasis and 40 matched controls underwent 1-μg cosyntropin testing. Baseline cortisol (mean difference -2.0 μg/dl, P=0.04) and 30-minute stimulated cortisol (mean difference -3.73 μg/dl, P=0.001) were significantly lower in patients with bronchiectasis. One patient had absolute adrenal insufficiency and 39.5 per cent (15/38) patients with bronchiectasis had impaired stimulated responses. Baseline and stimulated cortisol responses were unaffected by inhaled steroids (O.R 1.03, P=0.96). SGRQ scores were negatively correlated with body mass (r= -0.51, P=0.001) and bronchiectasis severity (r=0.37, P=0.019), but not related to baseline or stimulated cortisol responses. Interpretation & conclusions: Our results showed that the impaired adrenal responses to 1-μg cosyntropin were common in patients with bronchiectasis. This was not associated with the use of inhaled steroids or severity of bronchiectasis. Poor health status was associated with advanced disease and not with cortisol responses to the 1-μg cosyntropin test. PMID:24820833

Adrenal insufficiency in patients with stable non-cystic fibrosis bronchiectasis.

PubMed

Rajagopala, Srinivas; Ramakrishnan, Anantharaman; Bantwal, Ganapathi; Devaraj, Uma; Swamy, Smrita; Ayyar, S Vageesh; D'Souza, George

2014-03-01

Suppressed adrenal responses associated with inhaled steroid use have been reported in patients with bronchiectasis and have been shown to be associated with poor quality of life. This study was undertaken to examine the prevalence of suppressed cortisol responses in stable bronchiectasis and determine their correlation with the use of inhaled corticosteroids, radiologic severity of bronchiectasis and quality of life (QOL) scores. In this case-control study, cases were patients with bronchiectasis and suppressed cortisol responses and controls were healthy volunteers, and patients with bronchiectasis without suppressed cortisol responses. Symptoms, lung function test values, exercise capacity, HRCT severity scores for bronchiectasis, exacerbations, inhaled corticosteroid use and quality of life scores were compared between patients with and without suppressed cortisol values. Forty consecutive patients with bronchiectasis and 40 matched controls underwent 1-μg cosyntropin testing. Baseline cortisol (mean difference -2.0 μg/dl, P=0.04) and 30-minute stimulated cortisol (mean difference -3.73 μg/dl, P=0.001) were significantly lower in patients with bronchiectasis. One patient had absolute adrenal insufficiency and 39.5 per cent (15/38) patients with bronchiectasis had impaired stimulated responses. Baseline and stimulated cortisol responses were unaffected by inhaled steroids (O.R 1.03, P=0.96). SGRQ scores were negatively correlated with body mass (r= -0.51, P=0.001) and bronchiectasis severity (r=0.37, P=0.019), but not related to baseline or stimulated cortisol responses. Our results showed that the impaired adrenal responses to 1-μg cosyntropin were common in patients with bronchiectasis. This was not associated with the use of inhaled steroids or severity of bronchiectasis. Poor health status was associated with advanced disease and not with cortisol responses to the 1-μg cosyntropin test.

Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

PubMed Central

Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

2009-01-01

Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants. Conclusions We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoring the confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owing to its low effective population size in comparison with autosomal markers and therefore, special care should be taken in the interpretation of seeming signals of positive associations in mtDNA case-control association studies. PMID:20019817

[Occupational semicircular lipoatrophy associated with serum adipokine abnormalities].

PubMed

Reinoso-Barbero, Luis; Díaz-Garrido, Ramón; González-Gómez, María-Fernanda; Olarrea, José; Gómez-Gallego, Félix; Bandrés, Fernando

2015-10-21

The aim of this study was to examine the relationship between semicircular lipoatrophy (SL), inflammation marker (high sensibility C-reactive protein [hs-CRP]), adipokines (leptine, chemerine and vaspine) and autoimmune markers (rheumatoid factor [RF], C3 and C4 complement fractions, antinuclear antibodies [ANA], HLA DR3, and DR4). Chemerine is an adipokine, but also is an immunity marker. A case-control study was performed in May 2013; 21 cases were included. The closest healthy coworker to each case was used as a control. We calculated Kruskal-Wallis nonparametric test. We found statistical significance (P<.05) between SL and raised hs-CRP, raised leptine and low chemerine. i) There seems to be an underlying inflammatory component (raised hs-CRP) in SL; ii) adipokine alteration (raised leptine and low chemerine) supports the idea that adipocytic differentiation is affected in SL, and iii) we have not found any immune marker associated with SL, except chemerine itself, which could explain a possible association between SL and immunity. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

RISK FACTORS FOR SLOW GAIT SPEED: A NESTED CASE-CONTROL SECONDARY ANALYSIS OF THE MEXICAN HEALTH AND AGING STUDY.

PubMed

Pérez-Zepeda, M U; González-Chavero, J G; Salinas-Martinez, R; Gutiérrez-Robledo, L M

2015-01-01

Physical performance tests play a major role in the geriatric assessment. In particular, gait speed has shown to be useful for predicting adverse outcomes. However, risk factors for slow gait speed (slowness) are not clearly described. To determine risk factors associated with slowness in Mexican older adults. A two-step process was adopted for exploring the antecedent risk factors of slow gait speed. First, the cut-off values for gait speed were determined in a representative sample of Mexican older adults. Then, antecedent risk factors of slow gait speed (defined using the identified cut-points) were explored in a nested, cohort case-control study. One representative sample of a cross-sectional survey for the first step and the Mexican Health and Aging Study (a cohort characterized by a 10-year follow-up). A 4-meter usual gait speed test was conducted. Lowest gender and height-stratified groups were considered as defining slow gait speed. Sociodemographic characteristics, comorbidities, psychological and health-care related variables were explored to find those associated with the subsequent development of slow gait speed. Unadjusted and adjusted logistic regression models were performed. In the final model, age, diabetes, hypertension, and history of fractures were associated with the development of slow gait speed. Early identification of subjects at risk of developing slow gait speed may halt the path to disability due to the robust association of this physical performance test with functional decline.

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China.

PubMed

Wang, Fu-Ru; Fang, Qiao-Qiao; Tang, Wei-Ming; Xu, Xiao-San; Mahapatra, Tanmay; Mahapatra, Sanchita; Liu, Yu-Fei; Yu, Ning-Le; Sun, Quan-Fu

2015-01-01

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.

Novel Common Genetic Susceptibility Loci for Colorectal Cancer.

PubMed

Schmit, Stephanie L; Edlund, Christopher K; Schumacher, Fredrick R; Gong, Jian; Harrison, Tabitha A; Huyghe, Jeroen R; Qu, Chenxu; Melas, Marilena; Van Den Berg, David J; Wang, Hansong; Tring, Stephanie; Plummer, Sarah J; Albanes, Demetrius; Alonso, M Henar; Amos, Christopher I; Anton, Kristen; Aragaki, Aaron K; Arndt, Volker; Barry, Elizabeth L; Berndt, Sonja I; Bezieau, Stéphane; Bien, Stephanie; Bloomer, Amanda; Boehm, Juergen; Boutron-Ruault, Marie-Christine; Brenner, Hermann; Brezina, Stefanie; Buchanan, Daniel D; Butterbach, Katja; Caan, Bette J; Campbell, Peter T; Carlson, Christopher S; Castelao, Jose E; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Cheng, Iona; Cheng, Ya-Wen; Chin, Lee Soo; Church, James M; Church, Timothy; Coetzee, Gerhard A; Cotterchio, Michelle; Cruz Correa, Marcia; Curtis, Keith R; Duggan, David; Easton, Douglas F; English, Dallas; Feskens, Edith J M; Fischer, Rocky; FitzGerald, Liesel M; Fortini, Barbara K; Fritsche, Lars G; Fuchs, Charles S; Gago-Dominguez, Manuela; Gala, Manish; Gallinger, Steven J; Gauderman, W James; Giles, Graham G; Giovannucci, Edward L; Gogarten, Stephanie M; Gonzalez-Villalpando, Clicerio; Gonzalez-Villalpando, Elena M; Grady, William M; Greenson, Joel K; Gsur, Andrea; Gunter, Marc; Haiman, Christopher A; Hampe, Jochen; Harlid, Sophia; Harju, John F; Hayes, Richard B; Hofer, Philipp; Hoffmeister, Michael; Hopper, John L; Huang, Shu-Chen; Huerta, Jose Maria; Hudson, Thomas J; Hunter, David J; Idos, Gregory E; Iwasaki, Motoki; Jackson, Rebecca D; Jacobs, Eric J; Jee, Sun Ha; Jenkins, Mark A; Jia, Wei-Hua; Jiao, Shuo; Joshi, Amit D; Kolonel, Laurence N; Kono, Suminori; Kooperberg, Charles; Krogh, Vittorio; Kuehn, Tilman; Küry, Sébastien; LaCroix, Andrea; Laurie, Cecelia A; Lejbkowicz, Flavio; Lemire, Mathieu; Lenz, Heinz-Josef; Levine, David; Li, Christopher I; Li, Li; Lieb, Wolfgang; Lin, Yi; Lindor, Noralane M; Liu, Yun-Ru; Loupakis, Fotios; Lu, Yingchang; Luh, Frank; Ma, Jing; Mancao, Christoph; Manion, Frank J; Markowitz, Sanford D; Martin, Vicente; Matsuda, Koichi; Matsuo, Keitaro; McDonnell, Kevin J; McNeil, Caroline E; Milne, Roger; Molina, Antonio J; Mukherjee, Bhramar; Murphy, Neil; Newcomb, Polly A; Offit, Kenneth; Omichessan, Hanane; Palli, Domenico; Cotoré, Jesus P Paredes; Pérez-Mayoral, Julyann; Pharoah, Paul D; Potter, John D; Qu, Conghui; Raskin, Leon; Rennert, Gad; Rennert, Hedy S; Riggs, Bridget M; Schafmayer, Clemens; Schoen, Robert E; Sellers, Thomas A; Seminara, Daniela; Severi, Gianluca; Shi, Wei; Shibata, David; Shu, Xiao-Ou; Siegel, Erin M; Slattery, Martha L; Southey, Melissa; Stadler, Zsofia K; Stern, Mariana C; Stintzing, Sebastian; Taverna, Darin; Thibodeau, Stephen N; Thomas, Duncan C; Trichopoulou, Antonia; Tsugane, Shoichiro; Ulrich, Cornelia M; van Duijnhoven, Franzel J B; van Guelpan, Bethany; Vijai, Joseph; Virtamo, Jarmo; Weinstein, Stephanie J; White, Emily; Win, Aung Ko; Wolk, Alicja; Woods, Michael; Wu, Anna H; Wu, Kana; Xiang, Yong-Bing; Yen, Yun; Zanke, Brent W; Zeng, Yi-Xin; Zhang, Ben; Zubair, Niha; Kweon, Sun-Seog; Figueiredo, Jane C; Zheng, Wei; Marchand, Loic Le; Lindblom, Annika; Moreno, Victor; Peters, Ulrike; Casey, Graham; Hsu, Li; Conti, David V; Gruber, Stephen B

2018-06-16

Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection

PubMed Central

Salovin, Amy; Glanzman, Jason; Roslin, Kylie; Armangue, Thais; Panzer, Jessica A.

2018-01-01

Objective To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE). Methods Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort “Philadelphia” included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort “Barcelona” contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined. Results In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3–17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7–7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3–7.7, p = 0.007). Conclusion Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE. PMID:29629396

Anti-NMDA receptor encephalitis and nonencephalitic HSV-1 infection.

PubMed

Salovin, Amy; Glanzman, Jason; Roslin, Kylie; Armangue, Thais; Lynch, David R; Panzer, Jessica A

2018-07-01

To determine whether there is an association between nonencephalitic herpes simplex virus 1 (HSV-1) infection and anti-NMDA receptor encephalitis (anti-NMDARE). Antibody testing was performed using samples from 2 cohorts in a case-control observational study. The cohort "Philadelphia" included 16 serum samples of pediatric anti-NMDARE cases and 42 age-matched controls with other neuroinflammatory disorders studied at the Children's Hospital of Philadelphia and University of Pennsylvania. The cohort "Barcelona" contained 23 anti-NMDARE patient samples and 26 age-matched participants with other neuroinflammatory disorders studied at IDIBAPS-Hospital Clinic, University of Barcelona. The presence of HSV-1 IgG antibodies was examined by ELISA. As an additional control, IgG antibodies to cytomegalovirus (CMV) and Epstein-Barr virus viral capsid antigen (EBV-VCA) were determined. In each cohort, more participants with anti-NMDARE than controls had anti-HSV-1 IgG antibodies. In the Philadelphia cohort (58 participants), 44% of anti-NMDARE cases had antibodies to HSV-1 compared with 14% controls (OR 4.67, 95% CI 1.3-17.3, p = 0.031). In the Barcelona cohort (49 participants), 52% of participants with anti-NMDARE had antibodies to HSV-1 compared with 31% of controls (OR 2.45, 95% CI 0.7-7.9, p = 0.155). Overall, 49% of anti-NMDARE cases have antibodies to HSV-1 in these 2 combined cohorts compared with 21% of controls (Mantel-Haenszel OR 3.21, 95% CI 1.3-7.7, p = 0.007). Past HSV-1 infection was found in significantly more anti-NMDARE cases than controls. This suggests a meaningful association between nonencephalitic HSV-1 infection and development of anti-NMDARE.

Constructive thinking, rational intelligence and irritable bowel syndrome

PubMed Central

Rey, Enrique; Ortega, Marta Moreno; Alonso, Monica Olga Garcia; Diaz-Rubio, Manuel

2009-01-01

AIM: To evaluate rational and experiential intelligence in irritable bowel syndrome (IBS) sufferers. METHODS: We recruited 100 subjects with IBS as per Rome II criteria (50 consulters and 50 non-consulters) and 100 healthy controls, matched by age, sex and educational level. Cases and controls completed a clinical questionnaire (including symptom characteristics and medical consultation) and the following tests: rational-intelligence (Wechsler Adult Intelligence Scale, 3rd edition); experiential-intelligence (Constructive Thinking Inventory); personality (NEO personality inventory); psychopathology (MMPI-2), anxiety (state-trait anxiety inventory) and life events (social readjustment rating scale). Analysis of variance was used to compare the test results of IBS-sufferers and controls, and a logistic regression model was then constructed and adjusted for age, sex and educational level to evaluate any possible association with IBS. RESULTS: No differences were found between IBS cases and controls in terms of IQ (102.0 ± 10.8 vs 102.8 ± 12.6), but IBS sufferers scored significantly lower in global constructive thinking (43.7 ± 9.4 vs 49.6 ± 9.7). In the logistic regression model, global constructive thinking score was independently linked to suffering from IBS [OR 0.92 (0.87-0.97)], without significant OR for total IQ. CONCLUSION: IBS subjects do not show lower rational intelligence than controls, but lower experiential intelligence is nevertheless associated with IBS. PMID:19575489

The Association between Y Chromosome Microdeletion and Recurrent Pregnancy Loss.

PubMed

Ghorbian, S; Saliminejad, K; Sadeghi, M R; Javadi, Gh R; Kamali, K; Amirjannati, N; Bahreini, F; Edalatkhah, H; Khorram Khorshid, H R

2012-06-01

To date, the role of male factor contributing in evaluation of spontaneous recurrent pregnancy loss (RPL) has been less investigated and there is discrepancy in the role of Y chromosome microdeltions in RPL. Therefore, the current study was designed to examine whether Y chromosome microdeletions were associated with RPL in an Iranian population. One hundred men from couples, experiencing three or more RPLs, and one hundred normal men from couples with at least one child and no history of miscarriages as control group were included. Genomic DNA was extracted from peripheral blood and tested for Y chromosome microdeletions in AZFa, AZFb and AZFc regions using two multiplex PCR. None of the men in the case and control groups had any microdeletions in the AZFa, AZFb and AZFc regions. It seems that Y chromosome microdeletion is not associated with recurrent pregnancy loss, therefore performing this test in Iranian couples with RPL is not recommended.

Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype

PubMed Central

Traylor, Matthew; Adib-Samii, Poneh; Thijs, Vincent; Sudlow, Cathie; Rothwell, Peter M.; Boncoraglio, Giorgio; Dichgans, Martin; Meschia, James; Maguire, Jane; Levi, Christopher; Rost, Natalia S.; Rosand, Jonathan; Hassan, Ahamad; Bevan, Steve; Markus, Hugh S.

2016-01-01

Background and Purpose— Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels–associated genetic variant MTHFR C677T for association with magnetic resonance imaging–confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. Methods— We included 1359 magnetic resonance imaging–confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. Results— MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). Conclusions— MTHFR C677T was associated with magnetic resonance imaging–confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID:26839351

Control groups in paediatric epilepsy research: do first-degree cousins show familial effects?

PubMed

Hanson, Melissa; Morrison, Blaise; Jones, Jana E; Jackson, Daren C; Almane, Dace; Seidenberg, Michael; Zhao, Qianqian; Rathouz, Paul J; Hermann, Bruce P

2017-03-01

To determine whether first-degree cousins of children with idiopathic focal and genetic generalized epilepsies show any association across measures of cognition, behaviour, and brain structure. The presence/absence of associations addresses the question of whether and to what extent first-degree cousins may serve as unbiased controls in research addressing the cognitive, psychiatric, and neuroimaging features of paediatric epilepsies. Participants were children (aged 8-18) with epilepsy who had at least one first-degree cousin control enrolled in the study (n=37) and all enrolled cousin controls (n=100). Participants underwent neuropsychological assessment and brain imaging (cortical, subcortical, and cerebellar volumes), and parents completed the Child Behaviour Checklist (CBCL). Data (based on 42 outcome measures) from cousin controls were regressed on the corresponding epilepsy cognitive, behavioural, and imaging measures in a linear mixed model and case/control correlations were examined. Of the 42 uncorrected correlations involving cognitive, behavioural, and neuroimaging measures, only two were significant (p<0.05). The median correlation was 0.06. A test for whether the distribution of p values deviated from the null distribution under no association was not significant (p>0.25). Similar results held for the cognition/behaviour and brain imaging measures separately. Given the lack of association between cases and first-degree cousin performances on measures of cognition, behaviour, and neuroimaging, the results suggest a non-significant genetic influence on control group performance. First-degree cousins appear to be unbiased controls for cognitive, behavioural, and neuroimaging research in paediatric epilepsy.

Validation of prostate cancer risk-related loci identified from genome-wide association studies using family-based association analysis: evidence from the International Consortium for Prostate Cancer Genetics (ICPCG).

PubMed

Jin, Guangfu; Lu, Lingyi; Cooney, Kathleen A; Ray, Anna M; Zuhlke, Kimberly A; Lange, Ethan M; Cannon-Albright, Lisa A; Camp, Nicola J; Teerlink, Craig C; Fitzgerald, Liesel M; Stanford, Janet L; Wiley, Kathleen E; Isaacs, Sarah D; Walsh, Patrick C; Foulkes, William D; Giles, Graham G; Hopper, John L; Severi, Gianluca; Eeles, Ros; Easton, Doug; Kote-Jarai, Zsofia; Guy, Michelle; Rinckleb, Antje; Maier, Christiane; Vogel, Walther; Cancel-Tassin, Geraldine; Egrot, Christophe; Cussenot, Olivier; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; Wiklund, Fredrik; Grönberg, Henrik; Emanuelsson, Monica; Whittemore, Alice S; Oakley-Girvan, Ingrid; Hsieh, Chih-Lin; Wahlfors, Tiina; Tammela, Teuvo; Schleutker, Johanna; Catalona, William J; Zheng, S Lilly; Ostrander, Elaine A; Isaacs, William B; Xu, Jianfeng

2012-07-01

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families.

Neonatal factors among subjects diagnosed with a pervasive developmental disorder in the US.

PubMed

Geier, David; Kern, Janet; Geier, Mark

2018-07-01

Contradictory studies suggest that some neonatal factors may be associated with a pervasive developmental disorder (PDD) diagnosis, but limited data is available from longitudinal, prospective medical record assessments. The present hypothesis-testing longitudinal, case-control study evaluated birth characteristics among cases diagnosed with a PDD in comparison to controls by examining prospectively collected automated medical records within the Vaccine Safety Datalink (VSD) database. Cases were Health Maintenance Organization (HMO)-enrolled from birth until diagnosed with International Classification of Disease, 9th revision (ICD-9) PDD (299.xx) and controls were HMO-enrolled from birth for at least 4.75 years without a PDD diagnosis. The birth characteristics examined included: gender, gestational age in weeks at birth, mean birth weight in grams, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores at 1 minute and 5 minutes, and maternal age in years at birth. Cases had a significantly increased male/female ratio relative to controls. By contrast, mean gestational age at birth, mean birth weight, mean maternal age at birth, and mean APGAR scores at 1 minute and 5 minutes were not statistically different among cases compared to controls. This study indicates that cases diagnosed with a PDD as compared to controls do not have significant differences in neonatal factors.

RFC-1 80G>A polymorphism in case-mother/control-mother dyads is associated with risk of nephroblastoma and neuroblastoma.

PubMed

Montalvão-de-Azevedo, Rafaela; Vasconcelos, Gisele M; Vargas, Fernando R; Thuler, Luiz Claudio; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

2015-02-01

Embryonic tumors are associated with an interruption during normal organ development; they may be related to disturbances in the folate pathway involved in DNA synthesis, methylation, and repair. Prenatal supplementation with folic acid is associated with a decreased risk of neuroblastoma, brain tumors, retinoblastoma, and nephroblastoma. The aim of this study was to investigate the association between MTHFR rs1801133 (C677T) and RFC-1 rs1051266 (G80A) genotypes with the risk of developing nephroblastoma and neuroblastoma. Case-mother/control-mother dyad study. Samples from Brazilian children with nephroblastoma (n=80), neuroblastoma (n=66), healthy controls (n=453), and their mothers (case n=93; control n=75) were analyzed. Genomic DNA was isolated from peripheral blood cells and/or buccal cells and genotyped to identify MTHFR C677T and RFC-1 G80A polymorphisms. Differences in genotype distribution between patients and controls were tested by multiple logistic regression analysis. Risk for nephroblastoma and neuroblastoma was two- to fourfold increased among children with RFC-1 polymorphisms. An increased four- to eightfold risk for neuroblastoma and nephroblastoma was seen when the child and maternal genotypes were combined. Our results suggest that mother and child RFC-1 G80A genotypes play a role on the risk of neuroblastoma and nephroblastoma since this polymorphism may impair the intracellular levels of folate, through carrying fewer folate molecules to the cell interior, and thus, the intracellular concentration is not enough to maintain regular DNA synthesis and methylation pathways.

Community Participation, Dengue Fever Prevention and Control Practices in Swat, Pakistan.

PubMed

Zahir, Abdul; Ullah, Asad; Shah, Mussawar; Mussawar, Arsalan

2016-01-01

The aim of this study was to determine the role of community participation in prevention of dengue fever in The Swat district located in the Northern area of Khyber Pakhtunkhwa, Pakistan, which experienced a dengue fever outbreak in August, 2013. A total number of 8,963 dengue cases with 0.4% case fatality ratio were registered during the outbreak. A sample size of 354 respondents were proportionally allocated to each residential colony and then randomly selected. The association of independent variable (Community participation) and dependent variable (practices for control) were tested by using Chi Square test. Results regarding perception of practices for dengue control with community participation showed that: practices for control had significant association with organization of people to eradicate dengue mosquitoes (p=0.00), community leaders (p=0.04), community efforts (p≤0.01), use of insecticides by community people (p=0.00) and involvement of community people in awareness campaign (p=0.00). Similarly, significant associations were found between practices for control and community shared information during dengue outbreak (p=0.00), community link with health department, NGO, Other agencies (p=0.02). We conclude that the spread of dengue epidemic was aided by the ignorance, laziness of the community people and government agencies. However, the people, religious scholars, leaders and government agencies were not organized to participate in dengue prevention and eradication, hence, the chances of dengue infection increased in community. The study recommends mobilizing local communities and activating local leadership with active participation of Government and non-government organizations for initiation of preventive strategies.

Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.

PubMed

Kilarski, Laura L; Achterberg, Sefanja; Devan, William J; Traylor, Matthew; Malik, Rainer; Lindgren, Arne; Pare, Guillame; Sharma, Pankaj; Slowik, Agniesczka; Thijs, Vincent; Walters, Matthew; Worrall, Bradford B; Sale, Michele M; Algra, Ale; Kappelle, L Jaap; Wijmenga, Cisca; Norrving, Bo; Sandling, Johanna K; Rönnblom, Lars; Goris, An; Franke, Andre; Sudlow, Cathie; Rothwell, Peter M; Levi, Christopher; Holliday, Elizabeth G; Fornage, Myriam; Psaty, Bruce; Gretarsdottir, Solveig; Thorsteinsdottir, Unnar; Seshadri, Sudha; Mitchell, Braxton D; Kittner, Steven; Clarke, Robert; Hopewell, Jemma C; Bis, Joshua C; Boncoraglio, Giorgio B; Meschia, James; Ikram, M Arfan; Hansen, Bjorn M; Montaner, Joan; Thorleifsson, Gudmar; Stefanson, Kari; Rosand, Jonathan; de Bakker, Paul I W; Farrall, Martin; Dichgans, Martin; Markus, Hugh S; Bevan, Steve

2014-08-19

To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls. In an overall analysis of 17,970 cases of ischemic stroke and 70,764 controls, we identified a novel association on chromosome 12q24 (rs10744777, odds ratio [OR] 1.10 [1.07-1.13], p = 7.12 × 10(-11)) with ischemic stroke. The association was with all ischemic stroke rather than an individual stroke subtype, with similar effect sizes seen in different stroke subtypes. There was no association with intracerebral hemorrhage (OR 1.03 [0.90-1.17], p = 0.695). Our results show, for the first time, a genetic risk locus associated with ischemic stroke as a whole, rather than in a subtype-specific manner. This finding was not associated with intracerebral hemorrhage. © 2014 American Academy of Neurology.

Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts

PubMed Central

2013-01-01

Introduction Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. We aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk. Methods We conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. We studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. The statistically significant odds ratios were tested for noteworthiness using two Bayesian tests: false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). Results In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477). Conclusions Significant and noteworthy associations between several polymorphisms in circadian genes, night work and breast cancer risk were found among nurses who had worked at least three consecutive night shifts. PMID:23822714

Association between anal sac gland carcinoma and dog leukocyte antigen-DQB1 in the English Cocker Spaniel.

PubMed

Aguirre-Hernández, J; Polton, G; Kennedy, L J; Sargan, D R

2010-12-01

Anal sac gland carcinomas occur frequently in English Cocker Spaniels and, to a lesser extent, in other spaniel breeds. The disease typically presents in dogs aged 8 years or older and frequently metastasises to the local lymph nodes. The association between anal sac gland carcinoma in English Cocker Spaniels and the major histocompatibility complex class II loci (the dog leukocyte antigen loci DLA-DRB1, -DQA1, -DQB1) was investigated in 42 cases and 75 controls. Based on a corrected error rate of 0.017 for each test, the allele distribution in DLA-DRB1 showed no significant difference between cases and controls (P value = 0.019), while a significant difference was obtained for DLA-DQA1 and -DQB1 alleles (P values are 0.010 and 3.3 × 10⁻⁵). The DLA-DQB1*00701 allele was the most common in both cases and controls, but it had a higher frequency among the former (0.89) than in the latter (0.61), while the second most common allele had a higher frequency in the controls (0.23) than in the cases (0.07). Haplotype distributions were also significantly different between the two groups (P value = 1.61 × 10⁻⁴). This is the second disease in English Cocker Spaniels for which the most common DLA-DQB1 allele in the breed has been shown to have a higher frequency in cases than controls, while the second most common allele in the breed (*02001) has a significantly higher frequency in the controls, compared with the cases. © 2010 John Wiley & Sons A/S.

Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms.

PubMed

Tashjian, Robert Z; Granger, Erin K; Farnham, James M; Cannon-Albright, Lisa A; Teerlink, Craig C

2016-02-01

The precise etiology of rotator cuff disease is unknown, but prior evidence suggests a role for genetic factors. Limited data exist identifying specific genes associated with rotator cuff tearing. The purpose of this study was to identify specific genes or genetic variants associated with rotator cuff tearing by a genome-wide association study with an independent set of rotator cuff tear cases. A set of 311 full-thickness rotator cuff tear cases genotyped on the Illumina 5M single-nucleotide polymorphism (SNP) platform were used in a genome-wide association study with 2641 genetically matched white population controls available from the Illumina iControls database. Tests of association were performed with GEMMA software at 257,558 SNPs that compose the intersection of Illumina SNP platforms and that passed general quality control metrics. SNPs were considered significant if P < 1.94 × 10(-7) (Bonferroni correction: 0.05/257,558). Tests of association revealed 2 significantly associated SNPs, one occurring in SAP30BP (rs820218; P = 3.8E-9) on chromosome 17q25 and another occurring in SASH1 (rs12527089; P = 1.9E-7) on chromosome 6q24. This study represents the first attempt to identify genetic factors influencing rotator cuff tearing by a genome-wide association study using a dense/complete set of SNPs. Two SNPs were significantly associated with rotator cuff tearing, residing in SAP30BP on chromosome 17 and SASH1 on chromosome 6. Both genes are associated with the cellular process of apoptosis. Identification of potential genes or genetic variants associated with rotator cuff tearing may help in identifying individuals at risk for the development of rotator cuff tearing. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Usher syndrome associated with Fuchs' heterochromic uveitis.

PubMed

Lichtinger, Alejandro; Chowers, Itay; Amer, Radgonde

2010-10-01

The purpose of this study is to report two new cases of Usher syndrome associated with Fuchs' heterochromic uveitis (FHU), to confirm our previous observation of the association between FHU and retinitis pigmentosa (RP), and to evaluate if FHU is particularly associated with Usher syndrome. Retrospective medical record review of all new RP cases at Hadassah Medical Center between the years 2000 and 2007, review of our previously published data, and a meta-analysis of published relevant articles in peer reviewed journals. During the time frame of the study we diagnosed 58 new cases of RP, of whom one male and one female had the typical findings of FHU, and both had Usher syndrome type II. The difference in the occurrence of FHU between the 616 controls and the patients with RP was significant (p = 0.0073, Fisher's exact test). In our combined data, FHU occurred only in two types of RP; RP simplex with an incidence of 0.57%, and Usher syndrome with an incidence of 13.5%. This difference between the incidence of FHU in patients with Usher syndrome and other types of RP was significant (p < 0.0001, Fisher's exact test). Adding up these two cases with what is already published in the literature makes up a total of 17 RP patients with coexisting FHU. This study confirms the association between FHU and RP; and a particularly stronger association with Usher syndrome type II. Although infectious agents seem to play a role, the cause for this significant correlation is still unclear.

Neonatal jaundice: a risk factor for infantile autism?

PubMed

Maimburg, Rikke Damkjaer; Vaeth, Michael; Schendel, Diana Elizabeth; Bech, Bodil Hammer; Olsen, Jørn; Thorsen, Poul

2008-11-01

In a previous study, we found that infants transferred to a neonatal ward after delivery had an almost twofold increased risk of being diagnosed with infantile autism later in childhood in spite of extensive controlling of obstetric risk factors. We therefore decided to investigate other reasons for transfer to a neonatal ward, in particular hyperbilirubinaemia and neurological abnormalities. We conducted a population-based matched case-control study of 473 children with autism and 473 matched controls born from 1990 to 1999 in Denmark. Cases were children reported with a diagnosis of infantile autism in the Danish Psychiatric Central Register. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals [CI] and likelihood ratio tests were used to test for effect modification. We found an almost fourfold risk for infantile autism in infants who had hyperbilirubinaemia after birth (OR 3.7 [95% CI 1.3, 10.5]). In stratified analysis, the association appeared limited to term infants (>or=37 weeks gestation). A strong association was also observed between abnormal neurological signs after birth and infantile autism, especially hypertonicity (OR 6.7 [95% CI 1.5, 29.7]). No associations were found between infantile autism and low Apgar scores, acidosis or hypoglycaemia. Our findings suggest that hyperbilirubinaemia and neurological abnormalities in the neonatal period are important factors to consider when studying causes of infantile autism.

Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.

PubMed

Lee, Cha Gon; Lee, Jeehun; Lee, Munhyang

2018-01-01

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.

Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

PubMed

Jacquez, Geoffrey M; Shi, Chen; Meliker, Jaymie R

2015-01-01

In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation. Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race. Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed. Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.

Bad Behavior: Improving Reproducibility in Behavior Testing.

PubMed

Andrews, Anne M; Cheng, Xinyi; Altieri, Stefanie C; Yang, Hongyan

2018-01-24

Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.

Testing Pairwise Association between Spatially Autocorrelated Variables: A New Approach Using Surrogate Lattice Data

PubMed Central

Deblauwe, Vincent; Kennel, Pol; Couteron, Pierre

2012-01-01

Background Independence between observations is a standard prerequisite of traditional statistical tests of association. This condition is, however, violated when autocorrelation is present within the data. In the case of variables that are regularly sampled in space (i.e. lattice data or images), such as those provided by remote-sensing or geographical databases, this problem is particularly acute. Because analytic derivation of the null probability distribution of the test statistic (e.g. Pearson's r) is not always possible when autocorrelation is present, we propose instead the use of a Monte Carlo simulation with surrogate data. Methodology/Principal Findings The null hypothesis that two observed mapped variables are the result of independent pattern generating processes is tested here by generating sets of random image data while preserving the autocorrelation function of the original images. Surrogates are generated by matching the dual-tree complex wavelet spectra (and hence the autocorrelation functions) of white noise images with the spectra of the original images. The generated images can then be used to build the probability distribution function of any statistic of association under the null hypothesis. We demonstrate the validity of a statistical test of association based on these surrogates with both actual and synthetic data and compare it with a corrected parametric test and three existing methods that generate surrogates (randomization, random rotations and shifts, and iterative amplitude adjusted Fourier transform). Type I error control was excellent, even with strong and long-range autocorrelation, which is not the case for alternative methods. Conclusions/Significance The wavelet-based surrogates are particularly appropriate in cases where autocorrelation appears at all scales or is direction-dependent (anisotropy). We explore the potential of the method for association tests involving a lattice of binary data and discuss its potential for validation of species distribution models. An implementation of the method in Java for the generation of wavelet-based surrogates is available online as supporting material. PMID:23144961

EGFR amplification and expression in oral squamous cell carcinoma in young adults.

PubMed

Costa, V; Kowalski, L P; Coutinho-Camillo, C M; Begnami, M D; Calsavara, V F; Neves, J I; Kaminagakura, E

2018-07-01

The aim of this study was to investigate epidermal growth factor receptor (EGFR) gene alterations in two groups of patients with oral squamous cell carcinoma (OSCC) (a test group of subjects aged ≤40 years and a control group of subjects aged ≥50 years) and to associate the results with EGFR immunostaining, clinicopathological features, and the prognosis. Sixty cases of OSCC were selected (test group, n=21; control group, n=39). The tissue microarray technique was applied to ensure the uniformity of results. Gene amplification was analyzed by fluorescence in situ hybridization (FISH), and immunohistochemical staining for EGFR was analyzed using an automated imaging system. EGFR amplification was higher in the test group than in the control group (P=0.018) and was associated with advanced clinical stage (P=0.013), regardless of age. Patients with EGFR overexpression had worse survival rates, as did patients who had T3-T4 tumours and positive margins. EGFR overexpression has a negative impact on disease progression. Despite the higher amplification of EGFR in young adults, it does not significantly impact the survival rates of affected patients. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Intelligent image capture of cartridge cases for firearms examiners

NASA Astrophysics Data System (ADS)

Jones, Brett C.; Guerci, Joseph R.

1997-02-01

The FBI's DRUGFIRETM system is a nationwide computerized networked image database of ballistic forensic evidence. This evidence includes images of cartridge cases and bullets obtained from both crime scenes and controlled test firings of seized weapons. Currently, the system is installed in over 80 forensic labs across the country and has enjoyed a high degree of success. In this paper, we discuss some of the issues and methods associated with providing a front-end semi-automated image capture system that simultaneously satisfies the often conflicting criteria of the many human examiners visual perception versus the criteria associated with optimizing autonomous digital image correlation. Specifically, we detail the proposed processing chain of an intelligent image capture system (IICS), involving a real- time capture 'assistant,' which assesses the quality of the image under test utilizing a custom designed neural network.

A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006.

PubMed

Kendall, G M; Little, M P; Wakeford, R; Bunch, K J; Miles, J C H; Vincent, T J; Meara, J R; Murphy, M F G

2013-01-01

We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27,447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36,793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P=0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P=0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power ~50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels.

[Characteristics and habits of parents of children with insulin-dependent diabetes mellitus].

PubMed

Sipetić, Sandra; Vlajinac, Hristina; Kocev, Nikola; Radmanović, Slobodan

2003-01-01

The aim of this case-control study conducted in Belgrade during 1994-1997 was to investigate whether parental demographic characteristics and habits are associated with insulin-dependent diabetes mellitus (IDDM). Case group comprised 105 children up to 16 years old with IDDM and control group comprised 210 children with skin diseases. Cases and controls were individually matched by age (+/- one year), sex and place of residence (Belgrade). According to chi 2 test results, children with IDDM significantly had five or more family members and they also significantly more frequently had poor socio-economic status than their controls. Higher education of fathers was significantly more frequently reported in diabetic children, in comparison with their controls. Parents of diabetic children were significantly more frequently occupationally exposed to radiation, petroleum, and its derivates, organic solvents, dyes and lacquers. During pregnancy mothers of diabetic children significantly more frequently smoked cigarettes and consumed coffee, coca-cola, alcohol and foods containing nitrosamines. Fathers of diabetic children more frequently consumed alcohol.

Prostate-specific antigen screening and mortality from prostate cancer.

PubMed

Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

2008-03-01

There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

Prostate-Specific Antigen Screening and Mortality from Prostate Cancer

PubMed Central

Rhoads, George G.; Carson, Jeffrey L.; Merlino, Frances; Wilcox, Homer

2008-01-01

Background There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. Design, setting, and participants This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2–29.2% of cases and 21.8–26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality. PMID:18172740

Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

USDA-ARS?s Scientific Manuscript database

Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

Myocardial infarction risk and psychosocial work environment: an analysis of the male Swedish working force.

PubMed

Alfredsson, L; Karasek, R; Theorell, T

1982-01-01

The project was designed to test the assumption that certain psychosocial characteristics of occupational groups are associated with elevated myocardial infarction risk. All cases of myocardial infarction below the age of 65 in men living in the region of greater Stockholm during the years 1974-1976 were identified (deaths as well as survivals) in the official registries of hospitalizations and deaths. For each case two controls without infarction (in younger ages four) matched for age, area of residence and sex were selected randomly from the parish registries. For each case and control (n = 334 and 882, respectively) information was available regarding occupation. The psychosocial characteristics of each one of the 118 occupations were recorded by means of a nation wide interview survey (3876 working men) in 1977. Relative age-adjusted risks of developing a myocardial infarction were calculated for occupations in which many vs occupations in which few subjects reported a given characteristic (50% with most vs 50% with least). Shift work and monotony were associated with significant excess risk. Hectic work was not associated with excess risk by itself but in combination with variables associated with low decision latitude and/or few possibilities for growth it was associated with significant excess risk.

[Phenotype of patients with gynecomastia].

PubMed

Czajka-Oraniec, Izabella; Zgliczyński, Wojciech

2008-01-01

Gynecomastia, a benign enlargement of the breast glandular tissue in men. The aim of the study was to evaluate the phenotype of patients with gynecomastia, in particular antropometric assessment, breast ultrasound examination and hormonal testing, as well as to estimate possible causes of gynecomastia in studied population. Two hundred-twenty men were enrolled in the study: 126 patients with gynecomastia and 94 healthy volunteers as a control group. Detailed medical examination, breast ultrasound and hormonal assays for T, E2, LH, FSH, SHBG, S-DHEA, PRL and TSH were performed. Calculation of free testosterone concentration was done. The results of clinical and hormonal evaluation enabled to divide the cases into three groups: patients with idiopathic gynecomastia (58 subjects, 46%), with hypogonadism (34 subjects, 27%) and drug-induced or associated with other disorders gynecomastia (34 subjects, 27%). We found that men with gynecomastia, particularly associated with hypogonadism, had significantly higher BMI compared with control group. Ultrasound examination revealed the positive correlation between breast tissue volume and BMI, duration of gynecomastia and estradiol level, while negative correlation with testosterone level. We demonstrated significant differences in LH, T, SHBG, fT and S-DHEA levels between cases and controls. There were no differences in PRL, FSH and TSH levels among groups. Significant elevation of SHBG concentration in all groups of patients, including idiopathic gynecomastia cases, compared with controls, was remarkable. Clinical evaluation and hormonal profile can help to classify patient with gynecomastia into one of three groups: idiopathic gynecomastia, associated with hypogonadism, and drug-induced or associated with other diseases. Idiopathic gynecomastia - of unknown etiology is diagnosed in almost half of all cases (46%). We showed that apart from well known hormonal disturbances leading to gynecomastia, like hypogonadism or hyperestrogenism, also subtle hormonal alterations, such as sex hormone binding globuline (SHBG) level elevation may contribute to breast enlargement.

A case-control study of maternal periconceptual and pregnancy recreational drug use and fetal malformation using hair analysis.

PubMed

David, Anna L; Holloway, Andrew; Thomasson, Louise; Syngelaki, Argyro; Nicolaides, Kypros; Patel, Roshni R; Sommerlad, Brian; Wilson, Amie; Martin, William; Chitty, Lyn S

2014-01-01

Maternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method. In a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period). Women whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78 ± SD4.79 years, 18-37 vs 29.79 ± SD6 years, 18-42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08-4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18-0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20-10.02, p = 0.01). We demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age.

A Case-Control Study of Maternal Periconceptual and Pregnancy Recreational Drug Use and Fetal Malformation Using Hair Analysis

PubMed Central

David, Anna L.; Holloway, Andrew; Thomasson, Louise; Syngelaki, Argyro; Nicolaides, Kypros; Patel, Roshni R.; Sommerlad, Brian; Wilson, Amie; Martin, William; Chitty, Lyn S.

2014-01-01

Objective Maternal recreational drug use may be associated with the development of fetal malformations such as gastroschisis, brain and limb defects, the aetiology due to vascular disruption during organogenesis. Using forensic hair analysis we reported evidence of recreational drug use in 18% of women with a fetal gastroschisis. Here we investigate this association in a variety of fetal malformations using the same method. Methods In a multi-centre study, women with normal pregnancies (controls) and those with fetal abnormalities (cases) gave informed consent for hair analysis for recreational drug metabolites using mass spectrometry. Hair samples cut at the root were tested in sections corresponding to 3 month time periods (pre and periconceptual period). Results Women whose fetus had gastroschisis, compared to women with a normal control fetus, were younger (mean age 23.78±SD4.79 years, 18–37 vs 29.79±SD6 years, 18–42, p = 0.00001), were more likely to have evidence of recreational drug use (15, 25.4% vs 21, 13%, OR2.27, 95thCI 1.08–4.78, p = 0.028), and were less likely to report periconceptual folic acid use (31, 53.4% vs 124, 77.5%, OR0.33, 95thCI 0.18–0.63, p = 0.001). Age-matched normal control women were no less likely to test positive for recreational drugs than women whose fetus had gastroschisis. After accounting for all significant factors, only young maternal age remained significantly associated with gastroschisis. Women with a fetus affected by a non-neural tube central nervous system (CNS) anomaly were more likely to test positive for recreational drugs when compared to women whose fetus was normal (7, 35% vs 21, 13%, OR3.59, 95th CI1.20–10.02, p = 0.01). Conclusions We demonstrate a significant association between non neural tube CNS anomalies and recreational drug use in the periconceptual period, first or second trimesters, but we cannot confirm this association with gastroschisis. We confirm the association of gastroschisis with young maternal age. PMID:25360669

The role of ancestry in TB susceptibility of an admixed South African population.

PubMed

Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

2014-07-01

Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Puerperal Mastitis: a Reproductive Event of Importance Affecting Anti-Mucin Antibody Levels and Ovarian Cancer Risk

PubMed Central

Cramer, Daniel W.; Williams, Kristina; Vitonis, Allison F.; Yamamoto, Hidemi S.; Stuebe, Alison; Welch, William R.; Titus, Linda; Fichorova, Raina N.

2013-01-01

Purpose Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk for ovarian cancer. Methods In two case-control studies conducted in New England between 1998–2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n=200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95% confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models. Results Prior mastitis was associated with a significantly lower risk for ovarian cancer: OR (and 95% CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis; and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels. Conclusion Puerperal that mastitis may produce long-lasting anti-mucin antibodies that may lower the risk for ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10–20% of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens. PMID:23925696

Investigation of an outbreak of Salmonella enterica serovar Newport infection.

PubMed

Irvine, W N; Gillespie, I A; Smyth, F B; Rooney, P J; McClenaghan, A; Devine, M J; Tohani, V K

2009-10-01

A large outbreak of Salmonella enterica serotype Newport infection occurred in Northern Ireland during September and October 2004. Typing of isolates from patients confirmed that this strain was indistinguishable from that in concurrent outbreaks in regions of England, in Scotland and in the Isle of Man. A total of 130 cases were distributed unequally across local government district areas in Northern Ireland. The epidemic curve suggested a continued exposure over about 4 weeks. A matched case-control study of 23 cases and 39 controls found a statistically significant association with a history of having eaten lettuce in a meal outside the home and being a case (odds ratio 23.7, 95% confidence interval 1.4-404.3). This exposure was reported by 57% of cases. Although over 300 food samples were tested, none yielded any Salmonella spp. Complexity and limited traceability in salad vegetable distribution hindered further investigation of the ultimate source of the outbreak.

Frequency and determinants of thyroid autoimmunity in Ghanaian type 2 diabetes patients: a case-control study.

PubMed

Sarfo-Kantanka, Osei; Sarfo, Fred Stephen; Ansah, Eunice Oparebea; Yorke, Ernest; Akpalu, Josephine; Nkum, Bernard C; Eghan, Benjamin

2017-01-17

The link between type 1 diabetes and thyroid autoimmunity is well described. The same cannot be said for type 2 diabetes where results have been mixed so far. We investigated the prevalence and determinants of thyroid autoimmunity among Ghanaian type 2 diabetes patients. This was a case-control study involving 302 type 2 diabetes patients and 310 non - diabetic controls aged 40-80 years. Anthropometric and blood pressure measurements were obtained. Fasting samples were analyzed for glucose, thyroid function, and antibodies to thyroglobulin and thyroid peroxidase. The prevalence of thyroid autoimmunity was significantly higher among T2DM subjects (12.2% vs. 3.9%, p = 0.0004). Among T2DM subjects, 44 (14.7%) tested positive for TPOAb, 5 (1.7%) tested positive for TGAb and 15 (5.0%) tested positive for both autoantibodies. Females T2DM subjects showed a 3-fold increased risk of thyroid autoimmunity compared to males (OR:3.16, p =0.004), T2DM subjects with hyperthyroidism had a 41% increased risk of thyroid autoimmunity (OR: 1.41, p < 0.001), sub-clinical hyperthyroidism increased the risk of thyroid autoimmunity by 2 fold, (OR:2.19, p < 0.001), subclinical hypothyroidism increased the risk of autoimmunity by 4-fold, (OR:3.57 95% p < 0.0001), and hypothyroidism was associated with a 61% increased risk of thyroid autoimmunity (OR: 1.61,1.35-2.23). Dyslipidaemia was associated with a 44% increased risk of thyroid autoimmunity (OR: 1.44, p = 0.01) and a percentage increase in HbA1c was associated with 46% increased risk of thyroid autoimmunity (OR:1.46, p < 0.0001). We observed a high prevalence of thyroid autoimmunity in Ghanaian T2DM subjects compared to the general population. Thyroid autoimmunity in T2DM subjects was significantly associated with female gender, thyroid dysfunction, dyslipidaemia and poor glycemic control.

Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer

PubMed Central

Dai, Xiaoyu; Fang, Xiangming; Ma, Ying; Xianyu, Jianbo

2016-01-01

Abstract Benign prostatic hyperplasia (BPH) has been suggested to be a risk factor for certain urologic cancers, but the current evidence is inconsistent. The aim of this study was to investigate the association between BPH and urologic cancers. MEDLINE, EMBASE, Cochrane Library, and Web of Science were searched for potential eligible studies. We included case-control studies or cohort studies, which evaluated the association between BPH and urologic cancers (including prostate cancer, bladder cancer, kidney cancer, testicular cancer, or penile cancer). Overall effect estimates were calculated using the DerSimonian–Laird method for a random-effects model. Summary effect-size was calculated as risk ratio (RR), together with the 95% confidence interval (CI). This systematic review included 16 case-control studies and 10 cohort studies evaluating the association of BPH and prostate or bladder cancer; we did not identify any study about other urologic cancers. Meta-analyses demonstrated that BPH was associated with an increased incidence of prostate cancer (case-control study: RR = 3.93, 95% CI = 2.18–7.08; cohort-study: RR = 1.41, 95% CI = 1.00–1.99) and bladder cancer (case-control study: RR = 2.50, 95% CI = 1.63–3.84; cohort-study: RR = 1.58, 95% CI = 1.28–1.95). Subgroup analysis by ethnicity suggested that the association between BPH and prostate cancer was much stronger in Asians (RR = 6.09, 95% CI = 2.96–12.54) than in Caucasians (RR = 1.54, 95% CI = 1.19–2.01). Egger's tests indicated low risk of publication bias (prostate cancer: P = 0.11; bladder cancer: P = 0.95). BPH is associated with an increased risk of prostate cancer and bladder cancer. The risk of prostate cancer is particularly high in Asian BPH patients. Given the limitations of included studies, additional prospective studies with strict design are needed to confirm our findings. PMID:27149447

Lack of Association between Recurrent Pregnancy Loss and Inherited Thrombophilia in a Group of Colombian Patients

PubMed Central

Cardona, Henry; Castañeda, Serguei A.; Cardona Maya, Wálter; Alvarez, Leonor; Gómez, Joaquín; Gómez, Jorge; Torres, José; Tobón, Luis; Bedoya, Gabriel; Cadavid, Ángela P.

2012-01-01

Studies have shown an association between recurrent pregnancy loss and inherited thrombophilia in Caucasian populations, but there is insufficient knowledge concerning triethnic populations such as the Colombian. The aim of this study was to evaluate whether inherited thrombophilia is associated with recurrent pregnancy loss. Methods. We conducted a case-control study of 93 patients with recurrent pregnancy loss (cases) and 206 healthy multiparous women (controls) in a Colombian subpopulation. Three single nucleotide polymorphisms (SNPs) markers of the inherited thrombophilias factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T were genotyped by PCR-RFLP. Activated protein C resistance and plasma levels of antithrombin, protein C, and protein S were also measured. Results. The frequency of thrombophilia-associated SNPs, activated protein C resistance, and anticoagulant protein deficiencies, was low overall, except for the methylenetetrahydrofolate reductase C677T SNP. The differences between patients and controls had no statistical significance. Conclusion. Our study confirms the low prevalence of inherited thrombophilias in non-Caucasian populations and it is unlikely that the tested thrombophilias play a role in the pathogenesis of recurrent pregnancy loss in this Colombian population. PMID:22577540

Increased rate of positive penicillin skin tests among patients with glioma: insights into the association between allergies and glioma risk.

PubMed

Han, Sheng; Huang, Yanming; Wang, Zixun; Li, Zhonghua; Qin, Xiaofei; Wu, Anhua

2014-11-01

Allergy and immunoglobulin E levels are inversely associated with glioma risk. Previous studies have focused on respiratory and food allergies, and little information is available regarding drug allergies. This study evaluated the rate of positive penicillin skin tests (PenSTs) and blood eosinophil counts in a large population of patients with glioma compared with nontumor controls to provide evidence for the relationship between drug allergies and glioma risk. A retrospective case-control study was conducted in patients diagnosed with glioma (n = 913) between January 2004 and June 2013. The study patients were matched with nontumor controls (n = 1091) for age, sex, and date of admission to the hospital. Preoperative results of the PenST and eosinophil counts were obtained, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression models, while a Kaplan-Meier analysis was used to assess overall survival. The percentage of positive PenSTs was higher among patients with glioma than in control subjects. The age-, sex-, and admission date-adjusted OR for positive versus negative PenSTs was 2.392 (95% CI 1.891-3.026). Eosinophil counts were also higher in glioma cases than in controls: the OR for eosinophil > 0.06 × 10(9)/L versus ≤ 0.06 × 10(9)/L was 1.923 (95% CI 1.608-2.301). There was no association between positive PenST/eosinophil counts and glioma grade or patient survival (n = 105). In contrast to previously reported relationships between allergy and glioma, in the present study a significantly higher rate of positive PenSTs and higher eosinophil counts were found in patients with glioma than in nontumor controls. These results suggest a complex relationship between allergies and glioma development.

Comparison of Performance Characteristics of Aspergillus PCR in Testing a Range of Blood-Based Samples in Accordance with International Methodological Recommendations.

PubMed

Springer, Jan; White, P Lewis; Hamilton, Shanna; Michel, Denise; Barnes, Rosemary A; Einsele, Hermann; Löffler, Juergen

2016-03-01

Standardized methodologies for the molecular detection of invasive aspergillosis (IA) have been established by the European Aspergillus PCR Initiative for the testing of whole blood, serum, and plasma. While some comparison of the performance of Aspergillus PCR when testing these different sample types has been performed, no single study has evaluated all three using the recommended protocols. Standardized Aspergillus PCR was performed on 423 whole-blood pellets (WBP), 583 plasma samples, and 419 serum samples obtained from hematology patients according to the recommendations. This analysis formed a bicenter retrospective anonymous case-control study, with diagnosis according to the revised European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) consensus definitions (11 probable cases and 36 controls). Values for clinical performance using individual and combined samples were calculated. For all samples, PCR positivity was significantly associated with cases of IA (for plasma, P = 0.0019; for serum, P = 0.0049; and for WBP, P = 0.0089). Plasma PCR generated the highest sensitivity (91%); the sensitivities for serum and WBP PCR were 80% and 55%, respectively. The highest specificity was achieved when testing WBP (96%), which was significantly superior to the specificities achieved when testing serum (69%, P = 0.0238) and plasma (53%, P = 0.0002). No cases were PCR negative in all specimen types, and no controls were PCR positive in all specimens. This study confirms that Aspergillus PCR testing of plasma provides robust performance while utilizing commercial automated DNA extraction processes. Combining PCR testing of different blood fractions allows IA to be both confidently diagnosed and excluded. A requirement for multiple PCR-positive plasma samples provides similar diagnostic utility and is technically less demanding. Time to diagnosis may be enhanced by testing multiple contemporaneously obtained sample types. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

PubMed

Parodi, Stefano; Santi, Irene; Marani, Enza; Casella, Claudia; Puppo, Antonella; Garrone, Elsa; Fontana, Vincenzo; Stagnaro, Emanuele

2016-03-01

Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

Measurement methods and accuracy in copy number variation: failure to replicate associations of beta-defensin copy number with Crohn's disease.

PubMed

Aldhous, Marian C; Abu Bakar, Suhaili; Prescott, Natalie J; Palla, Raquel; Soo, Kimberley; Mansfield, John C; Mathew, Christopher G; Satsangi, Jack; Armour, John A L

2010-12-15

The copy number variation in beta-defensin genes on human chromosome 8 has been proposed to underlie susceptibility to inflammatory disorders, but presents considerable challenges for accurate typing on the scale required for adequately powered case-control studies. In this work, we have used accurate methods of copy number typing based on the paralogue ratio test (PRT) to assess beta-defensin copy number in more than 1500 UK DNA samples including more than 1000 cases of Crohn's disease. A subset of 625 samples was typed using both PRT-based methods and standard real-time PCR methods, from which direct comparisons highlight potentially serious shortcomings of a real-time PCR assay for typing this variant. Comparing our PRT-based results with two previous studies based only on real-time PCR, we find no evidence to support the reported association of Crohn's disease with either low or high beta-defensin copy number; furthermore, it is noteworthy that there are disagreements between different studies on the observed frequency distribution of copy number states among European controls. We suggest safeguards to be adopted in assessing and reporting the accuracy of copy number measurement, with particular emphasis on integer clustering of results, to avoid reporting of spurious associations in future case-control studies.

Association Between Androgenetic Alopecia and Coronary Artery Disease in Young Male Patients

PubMed Central

Sharma, Kamal H; Jindal, Anchal

2014-01-01

Background: Several studies have demonstrated an association between androgenetic alopecia (AGA) and cardiovascular disease. Still controversies exist regarding the association. Are they truly associated? Objective: The purpose of the present study was to assess the prevalence of AGA and establish its association in young (<45 years) Asian Indian Gujarati male patients having coronary artery disease (CAD). Materials and Methods: Case-control prospective multicentric study was carried out on 424 men. Case group consisted of 212 male subjects having CAD (Group 1) and another 212, either sibling or first degree male relative of the case subjects (having no evidence of CAD) were considered as the control group (Group 2). Age, total cholesterol, incidence of diabetes mellitus, and hypertension were similar in both groups. The degree of alopecia was assessed using the Norwood-Hamilton scale for men. Statistical analysis was performed using Chi-square test. Results: AGA was found in 80 (37.73%) young CAD patients (Group 1), whereas 44 (20.7%) of patients had alopecia in the control group (Group 2). There was statistically significant association between male AGA and CAD (P = 0.001). Odds ratio was 2.70 (95% confidence interval [CI], 1.72 ± 4.26). Statistically significant association was found between high grade baldness (Grades IV-VII) and CAD in young men (P < 0.05). Odds ratio = 2.36 (95% CI, 1.108 ± 5.033). There is statistically significant association of AGA in young Asian Gujarati male with CAD and the prevalence of AGA in young CAD patient is 37.73%. Conclusion: This study implies early onset AGA in male is independently associated with CAD, though mechanisms need to be investigated. PMID:25114445

A case-control study of risk factors for equine influenza spread onto horse premises during the 2007 epidemic in Australia.

PubMed

Firestone, Simon M; Schemann, Kathrin A; Toribio, Jenny-Ann L M L; Ward, Michael P; Dhand, Navneet K

2011-06-01

The 2007 epidemic of equine influenza in Australia provided an opportunity to investigate the effectiveness of on-farm biosecurity measures in preventing the spread of a novel pathogen in a largely naive population. We conducted a case-control study of 200 horse premises from highly affected regions of the state of New South Wales (NSW), to investigate risk factors for the spread of equine influenza onto horse premises, specifically, non-compliance with biosecurity measures recommended to horse owners by the relevant animal health authority, the NSW Department of Primary Industries. The study was restricted to cases occurring during the first seven weeks of the epidemic, a period prior to vaccination and the relaxation of some movement restrictions. Case and control premises were selected from a laboratory testing dataset and interviews were conducted with horse owners and managers on premises between July and November 2009. The proximity of premises to the nearest infected premises was the factor most strongly associated with case status. Case premises were more likely than control premises to be within 5 km and beyond 10 km of an infected premises. Having a footbath in place on the premises before any horses were infected was associated with a nearly four-fold reduction in odds of infection (odds ratio=0.27; 95% confidence interval: 0.09, 0.83). This protective association may have reflected overall premises biosecurity standards related to the fomite transmission of equine influenza. Compliance with certain on-farm biosecurity practices seemingly prevented horses on premises in high risk areas being infected with equine influenza during the 2007 outbreak in Australia. In future outbreaks, in addition to broader disease control measures, on-farm biosecurity practices should be adopted by horse owners and managers to prevent equine influenza spread. Copyright © 2011 Elsevier B.V. All rights reserved.

How Is Cancer Risk Measured?

MedlinePlus

... more groups. The people in one group (the control group ) may be given a standard screening test (if one exists) or no screening test. The ... for the human papillomavirus (HPV) and those who test negative for HPV. The ... Case-control studies Case-control studies are like cohort studies ...

APOC3 Promoter Polymorphisms C-482T and T-455C Are Associated with the Metabolic Syndrome1

PubMed Central

Miller, Michael; Rhyne, Jeffrey; Chen, Hegang; Beach, Valerie; Ericson, Richard; Luthra, Kalpana; Dwivedi, Manjari; Misra, Anoop

2007-01-01

Background Despite the growing epidemic of the metabolic syndrome (MetS), few studies have evaluated genetic polymorphisms associated with the MetS phenotype. One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss of insulin downregulation. Methods One hundred twenty two consecutive MetS cases were matched by age, sex and race in a 1:1 case-control design to evaluate the prevalence of common polymorphisms in the following candidate genes: APOC3, APOE, B3AR, FABP2, GNB3, LPL, and PPARα and PPARγ. Results Compared to controls, MetS subjects exhibited a greater prevalence of APOC3 promoter polymorphisms. Specifically, the frequency of the variant C-482T and T-455C alleles was 70.5 and 81.9% of cases compared to 43.4 and 54.1% in controls, respectively ( p <0.0001). Overall, APOC3 promoter variants were associated with a greater likelihood of MetS compared to wild type [C-482T (OR: 4.3; 95% CI: 2.2, 8.6 [p <0.0001]), T-455C (OR: 3.6; 95% CI: 2.0, 6.7 [p <0.0001])]. No material differences were identified between the other genetic variants tested and prevalence of MetS. Conclusions These data, therefore, suggest that the APOC3 promoter polymorphisms C-482T and T-455C are associated with the MetS. PMID:17416293

APOC3 promoter polymorphisms C-482T and T-455C are associated with the metabolic syndrome.

PubMed

Miller, Michael; Rhyne, Jeffrey; Chen, Hegang; Beach, Valerie; Ericson, Richard; Luthra, Kalpana; Dwivedi, Manjari; Misra, Anoop

2007-05-01

Despite the growing epidemic of the metabolic syndrome (MetS), few studies have evaluated genetic polymorphisms associated with the MetS phenotype. One candidate, APOC3, modulates lipid and lipoprotein metabolism and the promoter polymorphisms C-482T/T-455C are associated with loss of insulin downregulation. One hundred twenty two consecutive MetS cases were matched by age, sex and race in a 1:1 case-control design to evaluate the prevalence of common polymorphisms in the following candidate genes: APOC3, APOE, B3AR, FABP2, GNB3, LPL, and PPARalpha and PPARgamma. Compared to controls, MetS subjects exhibited a greater prevalence of APOC3 promoter polymorphisms. Specifically, the frequency of the variant C-482T and T-455C alleles was 70.5 and 81.9% of cases compared to 43.4 and 54.1% in controls, respectively (p <0.0001). Overall, APOC3 promoter variants were associated with a greater likelihood of MetS compared to wild type [C-482T (OR: 4.3; 95% CI: 2.2, 8.6 [p <0.0001]), T-455C (OR: 3.6; 95% CI: 2.0, 6.7 [p <0.0001])]. No material differences were identified between the other genetic variants tested and prevalence of MetS. These data, therefore, suggest that the APOC3 promoter polymorphisms C-482T and T-455C are associated with the MetS.

An outbreak of acute gastroenteritis associated with contaminated bottled water in a university - Jiangxi, China, 2012.

PubMed

Wang, Ruiping; Cheng, Huijian; Zong, Jun; Yu, Ping; Fu, Weijie; Yang, Fuqiang; Shi, Guoqing; Zeng, Guang

2012-10-01

On 23 May 2012, a university in Jiangxi, China reported a gastroenteritis outbreak. We investigated the outbreak to identify the agent, source and mode of transmission and to recommend control measures. A case was defined as any person from the university with onset of diarrhoea (≥ 3 times/24h) from 1 to 31 May 2012. Active case finding was conducted by reviewing university hospital and drug-store records and interviewing students, workers and teachers. We then conducted a case-control study in which we compared food, water and environmental exposure history. Water samples were collected and tested. We identified 417 cases - an attack rate (AR) of 4.7% (417/8781) for the university. There were 416 student cases (AR = 5.7%) distributed across all 11 colleges, five of which were more heavily affected (AR range = 5.9-14%). In the case-control study, cases had higher odds of having drunk bottled water (odds ratio [OR] = 4.1; 95% confidence interval [CI] = 1.7-9.9), and there was a dose-response relationship (χ(2)trend = 4.6, P < 0.05). Drinking boiled bottled water was inversely associated with being a case (OR = 0.22, 95% CI = 0.07-0.71). Eating in any of the three university canteens or drinking-water from the city water supply was not associated with being a case. Pathogenic Escherichia coli was isolated from two unopened bottled water specimens and from four student cases. This gastroenteritis outbreak was most likely caused by contaminated bottled water. The company in question has been shut down and no further cases have been reported. Increased regulation of bottled water plants and better coordination between different investigators for future outbreaks is recommended.

Joint analysis of binary and quantitative traits with data sharing and outcome-dependent sampling.

PubMed

Zheng, Gang; Wu, Colin O; Kwak, Minjung; Jiang, Wenhua; Joo, Jungnam; Lima, Joao A C

2012-04-01

We study the analysis of a joint association between a genetic marker with both binary (case-control) and quantitative (continuous) traits, where the quantitative trait values are only available for the cases due to data sharing and outcome-dependent sampling. Data sharing becomes common in genetic association studies, and the outcome-dependent sampling is the consequence of data sharing, under which a phenotype of interest is not measured for some subgroup. The trend test (or Pearson's test) and F-test are often, respectively, used to analyze the binary and quantitative traits. Because of the outcome-dependent sampling, the usual F-test can be applied using the subgroup with the observed quantitative traits. We propose a modified F-test by also incorporating the genotype frequencies of the subgroup whose traits are not observed. Further, a combination of this modified F-test and Pearson's test is proposed by Fisher's combination of their P-values as a joint analysis. Because of the correlation of the two analyses, we propose to use a Gamma (scaled chi-squared) distribution to fit the asymptotic null distribution for the joint analysis. The proposed modified F-test and the joint analysis can also be applied to test single trait association (either binary or quantitative trait). Through simulations, we identify the situations under which the proposed tests are more powerful than the existing ones. Application to a real dataset of rheumatoid arthritis is presented. © 2012 Wiley Periodicals, Inc.

Active Trachoma Cases in the Solomon Islands Have Varied Polymicrobial Community Structures but Do Not Associate with Individual Non-Chlamydial Pathogens of the Eye.

PubMed

Butcher, Robert M R; Sokana, Oliver; Jack, Kelvin; Kalae, Eric; Sui, Leslie; Russell, Charles; Houghton, Joanna; Palmer, Christine; Holland, Martin J; Le Mesurier, Richard T; Solomon, Anthony W; Mabey, David C W; Roberts, Chrissy H

2017-01-01

Several non-chlamydial microbial pathogens are associated with clinical signs of active trachoma in trachoma-endemic communities with a low prevalence of ocular Chlamydia trachomatis ( Ct ) infection. In the Solomon Islands, the prevalence of Ct among children is low despite the prevalence of active trachoma being moderate. Therefore, we set out to investigate whether active trachoma was associated with a common non-chlamydial infection or with a dominant polymicrobial community dysbiosis in the Solomon Islands. We studied DNA from conjunctival swabs collected from 257 Solomon Islanders with active trachoma and matched controls. Droplet digital PCR was used to test for pathogens suspected to be able to induce follicular conjunctivitis. Polymicrobial community diversity and composition were studied by sequencing of hypervariable regions of the 16S ribosomal ribonucleic acid gene in a subset of 54 cases and 53 controls. Although Ct was associated with active trachoma, the number of infections was low (cases, 3.9%; controls, 0.4%). Estimated prevalence (cases and controls, respectively) of each non-chlamydial infection was as follows: Staphylococcus aureus : 1.9 and 1.9%, Adenoviridae: 1.2 and 1.2%, coagulase-negative Staphylococcus : 5.8 and 4.3%, Haemophilus influenzae : 7.4 and 11.7%, Moraxella catarrhalis : 2.3 and 4.7%, and Streptococcus pneumoniae : 7.0 and 6.2%. There was no statistically significant association between the clinical signs of trachoma and the presence or load of any of the non- Ct infections that were assayed. Interindividual variations in the conjunctival microbiome were characterized by differences in the levels of Corynebacterium, Propionibacterium, Helicobacter , and Paracoccus , but diversity and relative abundance of these specific genera did not differ significantly between cases and controls. It is unlikely that the prevalent trachoma-like follicular conjunctivitis in this region of the Solomon Islands has a dominant bacterial etiology. Before implementing community-wide azithromycin distribution for trachoma, policy makers should consider that clinical signs of trachoma can be observed in the absence of any detectable azithromycin-susceptible organism.

Association between exposure to farm animals and pets and risk of Multiple Sclerosis.

PubMed

Siejka, Dylan; Taylor, Bruce; Ponsonby, Anne-Louise; Dwyer, Terence; van der Mei, Ingrid

2016-11-01

There exists inconsistent evidence regarding animals including pets as risk factors for the development of Multiple Sclerosis (MS). We investigated the association between farm animals and pets as possible environmental factors in MS development. Population based case-control study with 136 clinically definite MS cases and 272 controls randomly chosen from the community matched on sex and age. Data was collected from both questionnaire and a lifetime calendar detailing residence, occupation and pet/animal exposure over the course of participant's lives. Exposure to farming, livestock, specific farm animals and remoteness of residence showed no significant association with MS risk. Exposure to cats prior to disease onset was associated with a greater risk of MS (Adjusted Odds Ratio 2.46 (1.17-5.18)) but without a clear dose-response (test for trend, p=0.76). In contrast to other literature, farming and exposure to farm animals were not associated with MS. While we identified an association between cat exposure and MS, there was no dose-response relationship, and previous studies showed inconsistent results, leaving us to conclude that there is no strong evidence that exposure to cats is associated with MS. Copyright © 2016 Elsevier B.V. All rights reserved.

Candidate genes for COPD in two large data sets.

PubMed

Bakke, P S; Zhu, G; Gulsvik, A; Kong, X; Agusti, A G N; Calverley, P M A; Donner, C F; Levy, R D; Make, B J; Paré, P D; Rennard, S I; Vestbo, J; Wouters, E F M; Anderson, W; Lomas, D A; Silverman, E K; Pillai, S G

2011-02-01

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

The association between human papillomavirus infection and lung cancer: a system review and meta-analysis

PubMed Central

Xiong, Wei-Min; Xu, Qiu-Ping; Li, Xu; Xiao, Ren-Dong; Cai, Lin; He, Fei

2017-01-01

To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60–5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07–11.07), 2.59 (95% CI: 1.43–4.69) and 0.92 (95% CI: 0.63–1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07–4.76) and 2.25 (95% CI: 1.49–3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer. PMID:29221217

Fixation and its role in the causation, laterality and location of pterygium: a study in amblyopes and non-amblyopes.

PubMed

Sudhalkar, A

2012-03-01

To evaluate the role of fixation in causing pterygium and determining its laterality and location. This is a prospective, observational, case-control study. Cases were defined as patients with primary pterygium who had unilateral amblyopia with eccentric fixation. Controls were age-matched patients with primary pterygium, but without amblyopia and eccentric fixation. All patients underwent complete ocular, orthoptic, and systemic examination and a detailed risk-factor assessment (latitude of residence, exposure to sunlight, sand, and a high-reflectance environment). The role of fixation in the causation, laterality and location of pterygium was evaluated. Fisher's exact test, the unpaired t-test, and odds ratio (OR) were carried out to determine the significance of the observations. The mean age of subjects was 47.1±5.25 years in cases (n=107) and 48.2±4.75 years in controls (n=310; P=0.78). As far as known risk factors were concerned, both groups were evenly matched. Among the cases, 88 (82.2%) patients demonstrated suppression of the amblyopic eye and 19 (17.8%) patients had abnormal retinal correspondence (ARC). Patients with suppression had a unilateral pterygium in the better (fixating) eye, whereas those with ARC had bilateral pterygia. Among the controls, 192 (61.9%) eyes had bilateral pterygia and 118 (38.1%) eyes had unilateral pterygium. In controls, the dominant eye had a higher prevalence of pterygium. All patients in both groups had a nasal pterygium. Pterygium and fixation were strongly associated (P=0.007; Fisher's exact test; OR -15.98; P=0.008). Fixation appears to have an important role in causing pterygium and determining its location and laterality.

Dexamethasone Stimulated Gene Expression in Peripheral Blood is a Sensitive Marker for Glucocorticoid Receptor Resistance in Depressed Patients

PubMed Central

Menke, Andreas; Arloth, Janine; Pütz, Benno; Weber, Peter; Klengel, Torsten; Mehta, Divya; Gonik, Mariya; Rex-Haffner, Monika; Rubel, Jennifer; Uhr, Manfred; Lucae, Susanne; Deussing, Jan M; Müller-Myhsok, Bertram; Holsboer, Florian; Binder, Elisabeth B

2012-01-01

Although gene expression profiles in peripheral blood in major depression are not likely to identify genes directly involved in the pathomechanism of affective disorders, they may serve as biomarkers for this disorder. As previous studies using baseline gene expression profiles have provided mixed results, our approach was to use an in vivo dexamethasone challenge test and to compare glucocorticoid receptor (GR)-mediated changes in gene expression between depressed patients and healthy controls. Whole genome gene expression data (baseline and following GR-stimulation with 1.5 mg dexamethasone p.o.) from two independent cohorts were analyzed to identify gene expression pattern that would predict case and control status using a training (N=18 cases/18 controls) and a test cohort (N=11/13). Dexamethasone led to reproducible regulation of 2670 genes in controls and 1151 transcripts in cases. Several genes, including FKBP5 and DUSP1, previously associated with the pathophysiology of major depression, were found to be reliable markers of GR-activation. Using random forest analyses for classification, GR-stimulated gene expression outperformed baseline gene expression as a classifier for case and control status with a correct classification of 79.1 vs 41.6% in the test cohort. GR-stimulated gene expression performed best in dexamethasone non-suppressor patients (88.7% correctly classified with 100% sensitivity), but also correctly classified 77.3% of the suppressor patients (76.7% sensitivity), when using a refined set of 19 genes. Our study suggests that in vivo stimulated gene expression in peripheral blood cells could be a promising molecular marker of altered GR-functioning, an important component of the underlying pathology, in patients suffering from depressive episodes. PMID:22237309

Association between CYP19 gene SNP rs2414096 polymorphism and polycystic ovary syndrome in Chinese women.

PubMed

Jin, Jia-Li; Sun, Jing; Ge, Hui-Juan; Cao, Yun-Xia; Wu, Xiao-Ke; Liang, Feng-Jing; Sun, Hai-Xiang; Ke, Lu; Yi, Long; Wu, Zhi-Wei; Wang, Yong

2009-12-16

Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals. A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results. The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (P = 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls. Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.

Evaluation of Parkinson Disease Risk Variants as Expression-QTLs

PubMed Central

Latourelle, Jeanne C.; Dumitriu, Alexandra; Hadzi, Tiffany C.; Beach, Thomas G.; Myers, Richard H.

2012-01-01

The recent Parkinson Disease GWAS Consortium meta-analysis and replication study reports association at several previously confirmed risk loci SNCA, MAPT, GAK/DGKQ, and HLA and identified a novel risk locus at RIT2. To further explore functional consequences of these associations, we investigated modification of gene expression in prefrontal cortex brain samples of pathologically confirmed PD cases (N = 26) and controls (N = 24) by 67 associated SNPs in these 5 loci. Association between the eSNPs and expression was evaluated using a 2-degrees of freedom test of both association and difference in association between cases and controls, adjusted for relevant covariates. SNPs at each of the 5 loci were tested for cis-acting effects on all probes within 250 kb of each locus. Trans-effects of the SNPs on the 39,122 probes passing all QC on the microarray were also examined. From the analysis of cis-acting SNP effects, several SNPs in the MAPT region show significant association to multiple nearby probes, including two strongly correlated probes targeting the gene LOC644246 and the duplicated genes LRRC37A and LRRC37A2, and a third uncorrelated probe targeting the gene DCAKD. Significant cis-associations were also observed between SNPs and two probes targeting genes in the HLA region on chromosome 6. Expanding the association study to examine trans effects revealed an additional 23 SNP-probe associations reaching statistical significance (p<2.8×10−8) including SNPs from the SNCA, MAPT and RIT2 regions. These findings provide additional context for the interpretation of PD associated SNPs identified in recent GWAS as well as potential insight into the mechanisms underlying the observed SNP associations. PMID:23071545

Reverse shoulder arthroplasty for massive rotator cuff tear: risk factors for poor functional improvement.

PubMed

Hartzler, Robert U; Steen, Brandon M; Hussey, Michael M; Cusick, Michael C; Cottrell, Benjamin J; Clark, Rachel E; Frankle, Mark A

2015-11-01

Some patients unexpectedly have poor functional improvement after reverse shoulder arthroplasty (RSA) for massive rotator cuff tear without glenohumeral arthritis. Our aim was to identify risk factors for this outcome. We also assessed the value of RSA for cases with poor functional improvement vs. The study was a retrospective case-control analysis for primary RSA performed for massive rotator cuff tear without glenohumeral arthritis with minimum 2-year follow-up. Cases were defined as Simple Shoulder Test (SST) score improvement of ≤1, whereas controls improved SST score ≥2. Risk factors were chosen on the basis of previous association with poor outcomes after shoulder arthroplasty. Latissimus dorsi tendon transfer results were analyzed as a subgroup. Value was defined as improvement in American Shoulder and Elbow Surgeons (ASES) score per $10,000 hospital cost. In a multivariate binomial logistic regression analysis, neurologic dysfunction (P = .006), age <60 years (P = .02), and high preoperative SST score (P = .03) were independently associated with poor functional improvement. Latissimus dorsi tendon transfer patients significantly improved in active external rotation (-0.3° to 38.7°; P < .01). The value of RSA (ΔASES/$10,000 cost) for cases was 0.8 compared with 17.5 for controls (P < .0001). Young age, high preoperative function, and neurologic dysfunction were associated with poor functional improvement. Surgeons should consider these associations in counseling and selection of patients. Concurrent latissimus dorsi transfer was successful in restoring active external rotation in a subgroup of patients. The critical economic importance of improved patient selection is emphasized by the very low value of the procedure in the case group. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Resource Use and Costs Associated with Coeliac Disease before and after Diagnosis in 3,646 Cases: Results of a UK Primary Care Database Analysis

PubMed Central

Violato, Mara; Gray, Alastair; Papanicolas, Irini; Ouellet, Melissa

2012-01-01

Background Despite the considerable health impact of coeliac disease (CD), reliable estimates of the impact of diagnosis on health care use and costs are lacking. Aims To quantify the volume, type and costs, in a United Kingdom primary care setting, of healthcare resources used by individuals diagnosed with CD up to ten years before and after diagnosis, and to estimate medical costs associated with CD. Methods A cohort of 3,646 CD cases and a parallel cohort of 32,973 matched controls, extracted from the General Practice Research Database (GPRD) over the period 1987–2005 were used i) to evaluate the impact of diagnosis on the average resource use and costs of cases; ii) to assess direct healthcare costs due to CD by comparing average resource use and costs incurred by cases vs. controls. Results Average annual healthcare costs per patient increased by £310 (95% CI £299, £320) after diagnosis. CD cases experienced higher healthcare costs than controls both before diagnosis (mean difference £91; 95% CI: £86, £97) and after diagnosis (mean difference £354; 95% CI: £347, £361). These differences were driven mainly by higher test and referral costs before diagnosis, and by increased prescription costs after diagnosis. Conclusions This study shows significant additional primary care costs associated with coeliac disease. It provides novel evidence that will assist researchers evaluating interventions in this area, and will challenge policymakers, clinicians, researchers and the public to develop strategies that maximise the health benefits of the resources associated with this disease. PMID:22815991

What puts them at risk? A cross-sectional case-control survey of demographic profile and sexual behavior of patients with sexually transmitted infections at a tertiary care center in North India.

PubMed

Raj, Rama; Gupta, Vishal; Pathak, Mona; Sreenivas, Vishnubhatla; Sood, Seema; Singh, Sarman; Verma, Kaushal K; Khanna, Neena; Das, Bimal K; Gupta, Somesh

2017-01-01

Sexually transmitted infections (STIs) are a major public health problem in developing nations. Identification of risk factors can help in formulating effective strategies against them. The present study was conducted in a tertiary care hospital in North India over 1 year to identify the risk factors associated with STIs. A questionnaire-based cross-sectional case-control survey was conducted where participants answered questions on demographic details, sexual behavior, and awareness of STIs. Cases were patients with STIs whereas controls were randomly selected from healthy individuals accompanying patients with nonvenereal complaints attending our hospital. There were 106 cases and 64 controls. STI patients had sexual debut 2 years before controls. A higher proportion of STI cases had lower education, multiple sexual partners, lived separately from their partner, had nonregular partners, had protected sex in the last month, had sex under influence of alcohol/illicit drugs, sex in unstructured settings, and engaged in transactional sex, in comparison to controls ( P < 0.05). More cases were aware of the symptoms/preventive measures of STIs ( P < 0.001). On multivariate analysis, multiple sexual partners, sex under influence of alcohol/illicit drugs with nonregular partner, protected sex in the last month, and knowledge of preventive measures were found to be statistically associated with STIs ( P < 0.05). Our study identifies risk-behavior patterns in patients with STIs, which should be modified to reduce the burden of these diseases. Increasing the knowledge about STIs in these patients can translate into more common condom usage that lends support for strengthening sexual health programs at grass-root levels. The small size of the study population could have led to decreased power of the study to detect differences between cases and controls. The external validity of our results needs to be tested in different population groups involving larger sample sizes.

Pregnancy related listeriosis: treatment and control.

PubMed

Allerberger, Franz; Huhulescu, Steliana

2015-03-01

Listeriosis during pregnancy usually presents as an unremarkable febrile illness in the mother but can be fatal for the fetus and newborn. Reliable laboratory testing for early diagnosis is lacking. Serological antibody tests and bacteriological stool tests are not helpful since Listeria-specific antibodies and stool cultures yielding the organism can be found in healthy pregnant women. Because early diagnosis is difficult, diagnosis is usually made by culturing the pathogen from blood, cerebrospinal fluid, placenta or meconium. The mortality rate for fetal and newborn listeriosis remains approximately 20%. Two to three cases of pregnancy-associated listeriosis are reported annually in Austria among approximately 79,000 births, 20-30 cases are reported annually in Germany among approximately 680,000 births and 50-100 cases are reported annually in the USA among approximately 4 million births. Although Listeria infections in pregnancy are rare, they should be considered as a cause of fever of unknown origin during pregnancy.

Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus-Associated Pneumonia Among Children Aged <5 Years in the PERCH Study.

PubMed

Higdon, Melissa M; Le, Tham; O'Brien, Katherine L; Murdoch, David R; Prosperi, Christine; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Scott, J Anthony G; Thea, Donald M; Awori, Juliet O; Baillie, Vicky L; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N; Driscoll, Amanda J; Ebruke, Bernard E; Endtz, Hubert P; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A; Moore, David P; Park, Daniel E; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D; Zeger, Scott L; Deloria Knoll, Maria; Madhi, Shabir A

2017-06-15

Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Molecular markers of carcinogenesis for risk stratification of individuals with colorectal polyps: a case-control study.

PubMed

Gupta, Samir; Sun, Han; Yi, Sang; Storm, Joy; Xiao, Guanghua; Balasubramanian, Bijal A; Zhang, Song; Ashfaq, Raheela; Rockey, Don C

2014-10-01

Risk stratification using number, size, and histology of colorectal adenomas is currently suboptimal for identifying patients at increased risk for future colorectal cancer. We hypothesized that molecular markers of carcinogenesis in adenomas, measured via immunohistochemistry, may help identify high-risk patients. To test this hypothesis, we conducted a retrospective, 1:1 matched case-control study (n = 216; 46% female) in which cases were patients with colorectal cancer and synchronous adenoma and controls were patients with adenoma but no colorectal cancer at baseline or within 5 years of follow-up. In phase I of analyses, we compared expression of molecular markers of carcinogenesis in case and control adenomas, blind to case status. In phase II of analyses, patients were randomly divided into independent training and validation groups to develop a model for predicting case status. We found that seven markers [p53, p21, Cox-2, β-catenin (BCAT), DNA-dependent protein kinase (DNApkcs), survivin, and O6-methylguanine-DNA methyltransferase (MGMT)] were significantly associated with case status on unadjusted analyses, as well as analyses adjusted for age and advanced adenoma status (P < 0.01 for at least one marker component). When applied to the validation set, a predictive model using these seven markers showed substantial accuracy for identifying cases [area under the receiver operation characteristic curve (AUC), 0.83; 95% confidence interval (CI), 0.74-0.92]. A parsimonious model using three markers performed similarly to the seven-marker model (AUC, 0.84). In summary, we found that molecular markers of carcinogenesis distinguished adenomas from patients with and without colorectal cancer. Furthermore, we speculate that prospective studies using molecular markers to identify individuals with polyps at risk for future neoplasia are warranted. ©2014 American Association for Cancer Research.

Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

PubMed

McMahon, George; Ring, Susan M; Davey-Smith, George; Timpson, Nicholas J

2015-10-15

Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E - 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy. © The Author 2015. Published by Oxford University Press.

Use of vaporized hydrogen peroxide decontamination during an outbreak of multidrug-resistant Acinetobacter baumannii infection at a long-term acute care hospital.

PubMed

Ray, Amy; Perez, Federico; Beltramini, Amanda M; Jakubowycz, Marta; Dimick, Patricia; Jacobs, Michael R; Roman, Kathy; Bonomo, Robert A; Salata, Robert A

2010-12-01

To describe vaporized hydrogen peroxide (VHP) as an adjuvant in the control of multidrug-resistant (MDR) Acinetobacter baumannii infection in a long-term acute care hospital (LTACH) and to describe the risk factors for acquisition of MDR A. baumannii infection in the LTACH population. Outbreak investigation, case-control study, and before-after intervention trial. A 54-bed LTACH affiliated with a tertiary care center in northeastern Ohio. Investigation of outbreak with clinical and environmental cultures, antimicrobial susceptibility testing, polymerase chain reaction assay of repetitive chromosomal elements to type strains, and case-control study; and intervention consisting of comprehensive infection control measures and VHP environmental decontamination. Thirteen patients infected or colonized with MDR A. baumannii were identified from January 2008 through June 2008. By susceptibility testing, 10 (77%) of the 13 isolates were carbapenem-resistant. MDR A. baumannii was found in wound samples, blood, sputum, and urine. Wounds were identified as a risk factor for MDR A. baumannii colonization. Ventilator-associated pneumonia was the most common clinical syndrome caused by the pathogen, and the associated mortality was 14% (2 of the 13 case patients died). MDR A. baumannii was found in 8 of 93 environmental samples, including patient rooms and a wound care cart; environmental and clinical cultures were genetically related. Environmental cultures were negative immediately after VHP decontamination and both 24 hours and 1 week after VHP decontamination. Nosocomial acquisition of the pathogen in the LTACH ceased after VHP intervention. When patients colonized with MDR A. baumannii reoccupied rooms, environmental contamination recurred. Environmental decontamination using VHP combined with comprehensive infection control measures interrupted nosocomial transmission of MDR A. baumannii in an LTACH. The application of this novel approach to halt the transmission of MDR A. baumannii warrants further investigation.

The effect of rare variants on inflation of the test statistics in case-control analyses.

PubMed

Pirie, Ailith; Wood, Angela; Lush, Michael; Tyrer, Jonathan; Pharoah, Paul D P

2015-02-20

The detection of bias due to cryptic population structure is an important step in the evaluation of findings of genetic association studies. The standard method of measuring this bias in a genetic association study is to compare the observed median association test statistic to the expected median test statistic. This ratio is inflated in the presence of cryptic population structure. However, inflation may also be caused by the properties of the association test itself particularly in the analysis of rare variants. We compared the properties of the three most commonly used association tests: the likelihood ratio test, the Wald test and the score test when testing rare variants for association using simulated data. We found evidence of inflation in the median test statistics of the likelihood ratio and score tests for tests of variants with less than 20 heterozygotes across the sample, regardless of the total sample size. The test statistics for the Wald test were under-inflated at the median for variants below the same minor allele frequency. In a genetic association study, if a substantial proportion of the genetic variants tested have rare minor allele frequencies, the properties of the association test may mask the presence or absence of bias due to population structure. The use of either the likelihood ratio test or the score test is likely to lead to inflation in the median test statistic in the absence of population structure. In contrast, the use of the Wald test is likely to result in under-inflation of the median test statistic which may mask the presence of population structure.

Genetic characterization of Shigella spp. isolated from diarrhoeal and asymptomatic children.

PubMed

Ghosh, Santanu; Pazhani, Gururaja P; Niyogi, Swapan Kumar; Nataro, James P; Ramamurthy, Thandavarayan

2014-07-01

Phenotypic and genetic characteristics of Shigella spp. isolated from diarrhoeal and asymptomatic children aged up to 5 years were analysed in this study. In total, 91 and 17 isolates were identified from diarrhoeal (case) and asymptomatic (control) children, respectively. All the isolates were tested for antimicrobial resistance, the presence of integrons, plasmid-mediated quinolone resistance (PMQR), virulence-associated genes and Shigella pathogenicity island (SH-PAI). The majority of the Shigella spp. from cases (68.1%) and controls (82.3%) were found to be resistant to fluoroquinolones. Integron carriage was detected more in cases (76.9%) than in controls (35.5%). Atypical class 1 integron was detected exclusively in Shigella flexneri from cases but not from the controls. PMQR genes such as aac(6')-Ib-cr and qnrS1 were detected in 82.4 and 14.3% of the isolates from cases and in 53 and 17.6% in controls, respectively. Shigella isolates from cases as well as from controls were positive for the invasive plasmid antigen H-encoding gene ipaH. The other virulence genes such as virF, sat, setA, setB, sen and ial were detected in Shigella isolates in 80.2, 49.4, 27.4, 27.4, 80.2 and 79.1% of cases and in 64.7, 52.9, 17.6, 17.6, 64.7 and 64.7% of controls, respectively. The entire SH-PAI was detected in S. flexneri serotype 2a from cases and controls. In an isolate from a control child, the SH-PAI was truncated. Integrons, PMQR and virulence-encoding genes were detected more frequently in cases than in controls. In diarrhoea endemic areas, asymptomatic carriers may play a crucial role in the transmission of multidrug-resistant Shigella spp. with all the putative virulence genes. © 2014 The Authors.

Endemic Transmission of Visceral Leishmaniasis in Bhutan

PubMed Central

Yangzom, Thinley; Cruz, Israel; Bern, Caryn; Argaw, Daniel; den Boer, Margriet; Vélez, Iván Dario; Bhattacharya, Sujit K.; Molina, Ricardo; Alvar, Jorge

2012-01-01

Visceral leishmaniasis was first reported in Bhutan in 2006. We conducted studies of the parasite, possible vectors and reservoirs, and leishmanin skin test and risk factor surveys in three villages. Nineteen cases were reported from seven districts. Parasite typing yielded two novel microsatellite sequences, both related to Indian L. donovani. In one case village, 40 (18.5%) of 216 participants had positive leishmanin skin test results, compared with 3 (4.2%) of 72 in the other case village and 0 of 108 in the control village. Positive results were strongly associated with the village and increasing age. None of the tested dogs were infected. Eighteen sand flies were collected, 13 Phlebotomus species and 5 Sergentomyia species; polymerase chain reaction for leishmanial DNA was negative. This assessment suggests that endemic visceral leishmaniasis transmission has occurred in diverse locations in Bhutan. Surveillance, case investigations, and further parasite, vector, and reservoir studies are needed. The potential protective impact of bed nets should be evaluated. PMID:23091191

Tumor-based case-control studies of infection and cancer: muddling the when and where of molecular epidemiology.

PubMed

Engels, Eric A; Wacholder, Sholom; Katki, Hormuzd A; Chaturvedi, Anil K

2014-10-01

We describe the "tumor-based case-control" study as a type of epidemiologic study used to evaluate associations between infectious agents and cancer. These studies assess exposure using diseased tissues from affected individuals (i.e., evaluating tumor tissue for cancer cases), but they must utilize nondiseased tissues to assess control subjects, who do not have the disease of interest. This approach can lead to exposure misclassification in two ways. First, concerning the "when" of exposure assessment, retrospective assessment of tissues may not accurately measure exposure at the key earlier time point (i.e., during the etiologic window). Second, concerning the "where" of exposure assessment, use of different tissues in cases and controls can have different accuracy for detecting the exposure (i.e., differential exposure misclassification). We present an example concerning the association of human papillomavirus with various cancers, where tumor-based case-control studies likely overestimate risk associated with infection. In another example, we illustrate how tumor-based case-control studies of Helicobacter pylori and gastric cancer underestimate risk. Tumor-based case-control studies can demonstrate infection within tumor cells, providing qualitative information about disease etiology. However, measures of association calculated in tumor-based case-control studies are prone to over- or underestimating the relationship between infections and subsequent cancer risk. ©2014 American Association for Cancer Research.

Rare variant association analysis in case-parents studies by allowing for missing parental genotypes.

PubMed

Li, Yumei; Xiang, Yang; Xu, Chao; Shen, Hui; Deng, Hongwen

2018-01-15

The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes. In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding "complements" in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification. We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association.

The utility of caesarean myomectomy as a safe procedure: a retrospective analysis of 21 cases with review of literature.

PubMed

Kumar R, Ramesh; Patil, Manjula; Sa, Shruthi

2014-09-01

Myomectomy at the time of caesarean delivery has been discouraged because of the risk of intractable haemorrhage and increased postoperative morbidity. The aim of this study is to determine the safety and feasibility of caesarean myomectomy. A retrospective case control study done between June 2012 to May 2013 in a tertiary care teaching hospital in Karnataka, India which included 21 pregnant women with uterine fibroids who underwent myomectomy during caesarean section and were compared with 42 matched controls without uterine fibroids who had caesarean section alone during the same period. Primary outcome measures studied were incidence of haemorrhage and need for blood transfusion. Secondary outcome measures were duration of operation, length of hospital stay, postpartum fever and wound infection. Statistical analysis is done using IBMSPSS 20.0 software and students t-test. For calculation of incidence of haemorrhage Fisher's exact test is used. Mean age of the 21 cases was 31.81yrs and 47.62% were primigravida. Total 37 fibroids were removed. Subserosal were 30 cases(81.08%) while 1(2.07%) was submucous. 21(56.76%)fibroids were situated in fundal region and 3(8.11%) were in lower segment. Mean change in the haemoglobin from preoperative to postoperative period in the cases was 1.3gm/dl(±1.155mg/dl) and control was 1.05% (±.854mg/dl). Two of the cases(9.52%) required blood transfusion compared to none in control. None in either group required hysterectomy. Mean duration of surgery was 68.57min (±15.012min)and 51.55min (±9.595min) for controls which is statistically significant. This study shows that myomectomy during caesarean section is a safe procedure and is not associated with major intraoperative and postoperative complications.

Risk Factors Associated with MDR-TB at the Onset of Therapy among New Cases Registered with the RNTCP in Mumbai, India

PubMed Central

Atre, Sachin R.; D’Souza, Desiree T. B.; Vira, Tina S.; Chatterjee, Anirvan; Mistry, Nerges F.

2014-01-01

Background Multidrug-resistant TB (MDR-TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high-burden countries, including India. In hyper-endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR-TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. Objective To assess risk factors associated with MDR-TB among Category I, new sputum smear-positive cases, at the onset of therapy. Materials and Methods The study applied an unmatched case-control design for 514 patients (106 cases with MDR-TB strains and 408 controls with non-MDR-TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004-January 2007. Data were collected through semi-structured interviews and drug susceptibility test results. Results Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12-8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02-2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. Conclusion The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited. PMID:21727675

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults.

PubMed

Alexander, Freda E; Lawrence, Davia J; Freeland, June; Krajewski, Andrew S; Angus, Brian; Taylor, G Malcolm; Jarrett, Ruth F

2003-11-01

Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical HD, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV+ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were performed for the whole age range and separately for young (< 35 years) and old adults (> or = 35 years); formal tests of effect modification by age were included. For the young adults, reported IM in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.08-7.98 and OR = 5.22, 95% CI: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD. Copyright 2003 Wiley-Liss, Inc.

A modified case-control study of cryptosporidiosis (using non-Cryptosporidium-infected enteric cases as controls) in a community setting.

PubMed

Pintar, K D M; Pollari, F; Waltner-Toews, D; Charron, D F; McEwen, S A; Fazil, A; Nesbitt, A

2009-12-01

Data from the first sentinel site (Waterloo Region, Ontario) of the Canadian Integrated Enteric Disease Surveillance System (C-EnterNet) were used in a secondary-based case-control study of laboratory-confirmed Cryptosporidium infections to study the role of various exposure factors. The incidence of cryptosporidiosis in Waterloo Region was almost double both the provincial and national rates. Persons ill with one of nine other enteric infections (amoebiasis, campylobacteriosis, cyclosporiasis, giardiasis, listeriosis, salmonellosis, shigellosis, verotoxigenic E. coli infections, yersiniosis) captured by the surveillance system were used as the control group. Of 1204 cases of enteric illness in the sentinel area between April 2005 and December 2007, 36 cases and 803 controls were selected after excluding outbreak and international travel-related cases. Univariable analyses (Pearson chi2 and Fisher's exact tests) and multivariable logistic regression were performed. Results of the multivariable analysis found that cryptosporidiosis was associated with swimming in a lake or river (OR 2.9, 95% CI 1.2-7.4), drinking municipal water (a potential surrogate for urban respondents vs. rural) (OR 2.4, 95% CI 1.04-5.7), and having a family member with a diarrhoeal illness (OR 2.9, 95% CI 1.3-6.4).

Role of mtDNA haplogroups in the prevalence of osteoarthritis in different geographic populations: a meta-analysis.

PubMed

Shen, Jin-Ming; Feng, Lei; Feng, Chun

2014-01-01

Osteoarthritis (OA) is the most common form of arthritis and has become an increasingly important public-health problem. However, the pathogenesis of OA is still unclear. In recent years, its correlation with mtDNA haplogroups attracts much attention. We aimed to perform a meta-analysis to investigate the association between mtDNA haplogroups and OA. Published English or Chinese literature from PubMed, Web of Science, SDOS, and CNKI was retrieved up until April 15, 2014. Case-control or cohort studies that detected the frequency of mtDNA haplogroups in OA patients and controls were included. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) assessment. A meta-analysis was conducted to calculate pooled odds ratio (OR) with 95% confidence interval (CI) through the random or fixed effect model, which was selected based on the between-study heterogeneity assessed by Q test and I2 test. Subgroup analysis was performed to explore the origin of heterogeneity. A total of 6 case-control studies (10590 cases and 7161 controls) with an average NOS score of 6.9 were involved. For the analysis between mtDNA haplogroup J and OA, random model was selected due to high heterogeneity. No significant association was found initially (OR = 0.73, 95%CI: 0.52-1.03), however, once any study from UK population was removed the association emerged. Further subgroup analysis demonstrated that there was a significant association in Spain population (OR = 0.57, 95%CI: 0.46-0.71), but not in UK population. Also, subgroup analysis revealed that there was a significant correlation between cluster TJ and OA in Spain population (OR = 0.70, 95%CI: 0.58-0.84), although not in UK population. No significant correlation was found between haplogroup T/cluster HV/cluster KU and OA. Our current meta-analysis suggests that mtDNA haplogroup J and cluster TJ correlate with the risk of OA in Spanish population, but the associations in other populations require further investigation.