Sample records for population association analysis

  1. Accounting for linkage disequilibrium in association analysis of diverse populations.

    PubMed

    Charles, Bashira A; Shriner, Daniel; Rotimi, Charles N

    2014-04-01

    The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases. © 2014 WILEY PERIODICALS, INC.

  2. Lack of genetic association between TREM2 and Alzheimer's disease in East Asian population: a systematic review and meta-analysis.

    PubMed

    Huang, Man; Wang, Dejun; Xu, Zhijun; Xu, Yongshan; Xu, Xiaoping; Ma, Yuefeng; Xia, Zheng

    2015-09-01

    Large-scale genome-wide association studies have identified TREM2 variants to be significantly associated with Alzheimer's disease (AD) in caucasian population. The goal of this systematic study and meta-analysis was to assess the association between Triggering receptor expressed on myeloid cells 2 (TREM2) variants and AD in East Asian population. In this study, literatures were searched in PubMed, MEDLINE, EMBASE, and the Cochrane library to screen citations from January 1990 to June 2014. Data analysis was done by using the Stata 12 software. Twelve studies were considered for analysis. A total of 13 535 patients with AD and 22 976 healthy controls were studied. The results showed that rs75932628 variant was significantly associated with AD in caucasian population (P < .001, odds ratio ¼ 3.17, 95% confidence interval 2.45-4.09). However, the association was not found in East Asian population. In our study, we found that TREM2 variant is likely not associated with AD in East Asian population.

  3. Resequencing and association analysis of OXTR with autism spectrum disorder in a Japanese population.

    PubMed

    Egawa, Jun; Watanabe, Yuichiro; Shibuya, Masako; Endo, Taro; Sugimoto, Atsunori; Igeta, Hirofumi; Nunokawa, Ayako; Inoue, Emiko; Someya, Toshiyuki

    2015-03-01

    The oxytocin receptor (OXTR) is implicated in the pathophysiology of autism spectrum disorder (ASD). A recent study found a rare non-synonymous OXTR gene variation, rs35062132 (R376G), associated with ASD in a Japanese population. In order to investigate the association between rare non-synonymous OXTR variations and ASD, we resequenced OXTR and performed association analysis with ASD in a Japanese population. We resequenced the OXTR coding region in 213 ASD patients. Rare non-synonymous OXTR variations detected by resequencing were genotyped in 213 patients and 667 controls. We detected three rare non-synonymous variations: rs35062132 (R376G/C), rs151257822 (G334D), and g.8809426G>T (R150S). However, there was no significant association between these rare non-synonymous variations and ASD. Our present study does not support the contribution of rare non-synonymous OXTR variations to ASD susceptibility in the Japanese population. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

  4. Association between MTHFR C677T polymorphism and depression: a meta-analysis in the Chinese population.

    PubMed

    Jiang, Wei; Xu, Jun; Lu, Xiao-Jie; Sun, Yang

    2016-09-01

    Depression is a worldwide public health issue, and its prevalence increases each year. Although a number of studies have been conducted on the association between MTHFR C677T polymorphism and depression in China, this association remains elusive and controversial. To clarify the impact of MTHFR C677T polymorphism on the risk of depression, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure and Chinese Biology Medicine through May 5, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 13 case-control studies including 1895 patients and 1913 controls were involved in this meta-analysis. Overall, T variant of MTHFR C677T gene polymorphism was significantly associated with an increased risk of depression in the Chinese population (T vs. C: OR = 1.52, 95% CI = 1.24-1.85; TT + CT vs. CC: OR = 1.64, 95% CI = 1.16-2.30; TT vs. CC: OR = 2.19, 95% CI = 1.49-3.24; TT vs. CC + CT: OR = 1.80, 95% CI = 1.31-2.46). In subgroup analyses stratified by geographic area and source of controls, the significant results were found in population-based studies, in hospital-based studies, in North and South China. The risk conferred by MTHFR C677T polymorphism is higher in North China than in South China. In conclusion, this meta-analysis suggests that MTHFR C677T polymorphism is associated with depression in the Chinese population, but these associations vary in different geographic locations.

  5. Factors Associated with Variations in Population HIV Prevalence across West Africa: Findings from an Ecological Analysis

    PubMed Central

    Prudden, Holly J.; Beattie, Tara S.; Bobrova, Natalia; Panovska-Griffiths, Jasmina; Mukandavire, Zindoga; Gorgens, Marelize; Wilson, David; Watts, Charlotte H.

    2015-01-01

    Background Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this. Methods National, urban and rural data on HIV prevalence, the percentage of younger (15–24) and older (25–49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other. Findings National population HIV prevalence varies between 0 4–2 9% for men and 0 4–5.6% for women. ART coverage ranges from 6–23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence. Interpretation In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners. PMID:26698854

  6. Factors Associated with Variations in Population HIV Prevalence across West Africa: Findings from an Ecological Analysis.

    PubMed

    Prudden, Holly J; Beattie, Tara S; Bobrova, Natalia; Panovska-Griffiths, Jasmina; Mukandavire, Zindoga; Gorgens, Marelize; Wilson, David; Watts, Charlotte H

    2015-01-01

    Population HIV prevalence across West Africa varies substantially. We assess the national epidemiological and behavioural factors associated with this. National, urban and rural data on HIV prevalence, the percentage of younger (15-24) and older (25-49) women and men reporting multiple (2+) partners in the past year, HIV prevalence among female sex workers (FSWs), men who have bought sex in the past year (clients), and ART coverage, were compiled for 13 countries. An Ecological analysis using linear regression assessed which factors are associated with national variations in population female and male HIV prevalence, and with each other. National population HIV prevalence varies between 0 4-2 9% for men and 0 4-5.6% for women. ART coverage ranges from 6-23%. National variations in HIV prevalence are not shown to be associated with variations in HIV prevalence among FSWs or clients. Instead they are associated with variations in the percentage of younger and older males and females reporting multiple partners. HIV prevalence is weakly negatively associated with ART coverage, implying it is not increased survival that is the cause of variations in HIV prevalence. FSWs and younger female HIV prevalence are associated with client population sizes, especially older men. Younger female HIV prevalence is strongly associated with older male and female HIV prevalence. In West Africa, population HIV prevalence is not significantly higher in countries with high FSW HIV prevalence. Our analysis suggests, higher prevalence occurs where more men buy sex, and where a higher percentage of younger women, and older men and women have multiple partnerships. If a sexual network between clients and young females exists, clients may potentially bridge infection to younger females. HIV prevention should focus both on commercial sex and transmission between clients and younger females with multiple partners.

  7. Volatility and Growth in Populations of Rural Associations

    ERIC Educational Resources Information Center

    Wollebaek, Dag

    2010-01-01

    This article uses unique community-level data aggregated from censuses of associations to analyze growth and volatility in rural populations of grassroots associations. A qualitative comparative analysis (QCA) shows that the two main paths to growth were (1) centralization in polycephalous (multicentered) municipalities and (2) population growth…

  8. Genetic association of RIT2 rs12456492 polymorphism and Parkinson's disease susceptibility in Asian populations: a meta-analysis.

    PubMed

    Lu, Yanjun; Liu, Wei; Tan, Kun; Peng, Jing; Zhu, Yaowu; Wang, Xiong

    2015-09-03

    Recent studies investigating the association of the Ras-like without CAAX 2 (RIT2) polymorphism, rs12456492, with Parkinson's disease (PD) are controversial. We performed a meta-analysis to study the association between rs12456492 and PD susceptibility in Asian populations. Literature searches of PubMed and Embase were performed up to June 3, 2015, and the strength of the association between rs12456492 and PD was evaluated by odds ratios (OR) and 95% confidence intervals (CI). Four studies conducted between 2013 and 2015, comprising 2017 PD cases and 2010 controls, were included in the meta-analysis. Significant association of rs12456492 with PD was found in the dominant (GG + AG vs. AA: OR = 1.26, 95% CI = 1.20-1.44, P = 0.00) and additive models (GG vs. AA: OR = 1.38, 95% CI = 1.03-1.83, P = 0.030). Although sensitivity analysis found that the overall result was stable only in the dominant genetic model, a publication bias was also detected. Therefore, the results should be treated with caution. The current meta-analysis suggested that rs12456492 might be associated with increased PD risk in Asian populations, but studies using larger sample sizes and different ethnic populations will be needed to further confirm this association.

  9. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice.

    PubMed

    Pradhan, Sharat Kumar; Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai; Pandit, Elssa

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance.

  10. Population Structure, Genetic Diversity and Molecular Marker-Trait Association Analysis for High Temperature Stress Tolerance in Rice

    PubMed Central

    Barik, Saumya Ranjan; Sahoo, Ambika; Mohapatra, Sudipti; Nayak, Deepak Kumar; Mahender, Anumalla; Meher, Jitandriya; Anandan, Annamalai

    2016-01-01

    Rice exhibits enormous genetic diversity, population structure and molecular marker-traits associated with abiotic stress tolerance to high temperature stress. A set of breeding lines and landraces representing 240 germplasm lines were studied. Based on spikelet fertility percent under high temperature, tolerant genotypes were broadly classified into four classes. Genetic diversity indicated a moderate level of genetic base of the population for the trait studied. Wright’s F statistic estimates showed a deviation of Hardy-Weinberg expectation in the population. The analysis of molecular variance revealed 25 percent variation between population, 61 percent among individuals and 14 percent within individuals in the set. The STRUCTURE analysis categorized the entire population into three sub-populations and suggested that most of the landraces in each sub-population had a common primary ancestor with few admix individuals. The composition of materials in the panel showed the presence of many QTLs representing the entire genome for the expression of tolerance. The strongly associated marker RM547 tagged with spikelet fertility under stress and the markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling the high temperature stress tolerance were detected through both mixed linear model and general linear model TASSEL analysis. These markers can be deployed as a resource for marker-assisted breeding program of high temperature stress tolerance. PMID:27494320

  11. Meta-analysis indicates that SNP rs9939609 within FTO is not associated with major depressive disorder (MDD) in Asian population.

    PubMed

    Yao, Yao; Wen, Yueqiang; Du, Tingfu; Sun, Ning; Deng, Hong; Ryan, Joanne; Rao, Shuquan

    2016-03-15

    Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control samples totaling 6531 cases and 12,359 controls. Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). The age distribution and gender ratios were not matched well in the combined samples of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Association between the interleukin-1β C-511T polymorphism and periodontitis: a meta-analysis in the Chinese population.

    PubMed

    Wang, H F; He, F Q; Xu, C J; Li, D M; Sun, X J; Chi, Y T; Guo, W

    2017-02-23

    The association between the interleukin-1 beta (IL-1β) C-511T (or rs16944) polymorphism and periodontitis remains inconclusive, even though there have been previous studies on this association. To assess the effects of IL-1β C-511T variants on the risk of development of periodontitis, a meta-analysis was performed in a single ethnic population. Studies, published up to December 2015, were selected for the meta-analysis from PubMed and Chinese databases. The associations were assessed with pooled OR and 95%CI. This meta-analysis identified 8 studies, including 1276 periodontitis cases and 1558 controls. Overall, a significant association between the IL-1β C-511T polymorphism and periodontitis was found in the Chinese population (TT vs CC: OR = 1.48, 95%CI = 1.19-1.85; TT + CT vs CC: OR = 1.50, 95%CI = 1.25-1.81; T vs C: OR = 1.33, 95%CI = 1.06-1.68). In the subgroup analyses based on geographical area(s), source of controls, and type of periodontitis, significant results were obtained for the association between IL-1β C-511T variants and periodontitis. Our meta-analysis indicated that the IL-1β C-511T polymorphism may be a genetic susceptibility factor for periodontitis in the Chinese population. This marker could be used to identify Chinese individuals at a high risk for periodontitis.

  13. Polymorphisms in peptidylarginine deiminase associate with rheumatoid arthritis in diverse Asian populations: evidence from MyEIRA study and meta-analysis

    PubMed Central

    2012-01-01

    Introduction The majority of our knowledge regarding disease-related mechanisms of uncontrolled citrullination and anti-citrullinated protein antibody development in rheumatoid arthritis (RA) was investigated in Caucasian populations. However, peptidylarginine deiminase (PADI) type 4 gene polymorphisms are associated with RA in East Asian populations and weak or no association was found in Caucasian populations. This study explores the association between the PADI4 polymorphisms and RA risk in a multiethnic population residing in South East Asia with the goal of elucidating generalizability of association in non-Caucasian populations. Methods A total of 320 SNPs from the PADI locus (including PADI1, PADI2, PADI3, PADI4 and PADI6 genes) were genotyped in 1,238 RA cases and 1,571 control subjects from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) case-control study. Additionally, we conducted meta-analysis of our data together with the previously published studies of RA from East Asian populations. Results The overall odds ratio (ORoverall) for the PADI4 (rs2240340) allelic model was 1.11 (95% confidence interval (CI) = 1.00 to 1.23, P = 0.04) and for the genotypic model was 1.20 (95% CI = 1.01 to 1.44, P = 0.04). Haplotype analysis for four selected PADI4 SNPs revealed a significant association of one with susceptibility (P = 0.001) and of another with a protective effect (P = 0.02). The RA susceptibility was further confirmed when combined meta-analysis was performed using these data together with data from five previously published studies from Asia comprising 5,192 RA cases and 4,317 control subjects (ORoverall = 1.23 (95% CI = 1.16 to 1.31, Pheterogeneity = 0.08) and 1.31 (95% CI = 1.20 to 1.44, Pheterogeneity = 0.32) in allele and genotype-based models, respectively). In addition, we also detected a novel association of PADI2 genetic variant rs1005753 with RA (ORoverall = 0.87 (95% CI = 0.77 to 0.99)). Conclusion Our study

  14. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    PubMed Central

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

  15. Association analysis between genetic variants in interleukin genes among different populations with hyperuricemia in Xinjiang Autonomous Region

    PubMed Central

    Zhang, Bei; Sun, Yuping; Li, Yuanyuan; Yu, Jiahui; Wang, Tingting; Xia, He; Li, Changgui; Liu, Shiguo; Yao, Hua

    2015-01-01

    To investigate whether functional variants of five interleukin genes (IL-1β, IL-10, IL-8, IL-18 and IL-18RAP) are associated with susceptibility to hyperuricemia among different nationalities (including Uygur, Kazak and Han populations) in the Xinjiang Autonomous Region of China. A total of 884 hyperuricemia patients and 1316 matched controls were recruited from the First Affiliated Hospital of Xinjiang Medical University in Urumqi. After genotyping of rs4073 in IL-8, rs16944 in IL-1, rs187238 in IL-18, rs1800871 in IL-10 and rs13015714 in IL-18RAP by TaqMan allele discrimination assays, an association analysis was performed using the χ2 test as well as a genotype-phenotype analysis. For the Uygur population, IL-8 rs4073, IL-18 rs187238 and IL-18RAP rs130154 polymorphisms were all associated with hyperuricemia (P<0.001 by genotype and P=0.008, OR 0.802 by allele for IL-8; P=0.01 by genotype and P=0.006, OR 1.332 by allele for IL-18 rs187238; P=0.007 by genotype and P=0.005, OR 1.27 by allele for IL-18RAP rs130154). For the Kazak population, only IL-18 rs187238 showed statistical significance with hyperuricemia (P=0.002 by genotype and P=0.007, OR 1.823 by allele). However, no differences were found between the five SNPs and hyperuricemia among the Han population. This study demonstrated genetic polymorphisms of different interleukin genes related to hyperuricemia vary in different nationalities in the Xinjiang Autonomous Region because of different geographical environments. IL-8, IL-1RL1 and IL-18 might be involved in the development of hyperuricemia in the Uygur population, whereas only IL-18 might be involved in the Kazak population. PMID:26722554

  16. Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease.

    PubMed

    Oliveira, Marisa; Saraiva, Diana P; Cavadas, Bruno; Fernandes, Verónica; Pedro, Nicole; Casademont, Isabelle; Koeth, Fanny; Alshamali, Farida; Harich, Nourdin; Cherni, Lotfi; Sierra, Beatriz; Guzman, Maria G; Sakuntabhai, Anavaj; Pereira, Luisa

    2018-04-17

    Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely naïve European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    PubMed

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

  18. Associations of Urinary Cotinine-Verified Active and Passive Smoking with Thyroid Function: Analysis of Population-Based Nationally Representative Data.

    PubMed

    Kang, Jihun; Kong, Eunhee; Choi, Jongsoon

    2018-05-01

    The effects of active and passive smoking on thyroid function in the Korean population have not been determined. Furthermore, related research is based on self-reported smoking status, which may be inaccurate, especially among women. The present study aimed at evaluating the association between biochemically verified smoking status and thyroid function in a nationally representative Korean population. This population-based cross-sectional study included 3404 subjects without thyroid disease who were not taking thyroid medication. Smoking status was identified using self-reported data and urinary cotinine levels. Kruskal-Wallis and Jonckheere-Terpstra trend tests were performed to evaluate the association between smoking exposure and thyroid function. Multivariate logistic regression analysis was used to estimate the effect of smoking on subclinical hypothyroidism (SCH). Biochemically verified active and passive smoking rates were 43.4% and 23.3% among men and 10.0% and 22.9% among women, respectively. Active smokers had significantly lower iodine levels than passive smokers and nonsmokers. Active smoking was associated with decreased serum thyrotropin (TSH) levels among both sexes, although only men exhibited a dose-response relationship between increasing smoking exposure and decreasing TSH levels. Passive smoking slightly decreased TSH levels, but the decrease was not statistically significant. The risk of SCH decreased with increasing smoking exposure in the multivariate-adjusted analysis (p for trend = 0.027 among men and 0.042 among women). Active and passive smoking were associated with decreasing serum TSH levels and a lower risk of SCH in a Korean population. These associations might be related to lower urinary iodine levels in active smokers.

  19. A general population-genetic model for the production by population structure of spurious genotype-phenotype associations in discrete, admixed or spatially distributed populations.

    PubMed

    Rosenberg, Noah A; Nordborg, Magnus

    2006-07-01

    In linkage disequilibrium mapping of genetic variants causally associated with phenotypes, spurious associations can potentially be generated by any of a variety of types of population structure. However, mathematical theory of the production of spurious associations has largely been restricted to population structure models that involve the sampling of individuals from a collection of discrete subpopulations. Here, we introduce a general model of spurious association in structured populations, appropriate whether the population structure involves discrete groups, admixture among such groups, or continuous variation across space. Under the assumptions of the model, we find that a single common principle--applicable to both the discrete and admixed settings as well as to spatial populations--gives a necessary and sufficient condition for the occurrence of spurious associations. Using a mathematical connection between the discrete and admixed cases, we show that in admixed populations, spurious associations are less severe than in corresponding mixtures of discrete subpopulations, especially when the variance of admixture across individuals is small. This observation, together with the results of simulations that examine the relative influences of various model parameters, has important implications for the design and analysis of genetic association studies in structured populations.

  20. Neighborhood social capital is associated with participation in health checks of a general population: a multilevel analysis of a population-based lifestyle intervention- the Inter99 study.

    PubMed

    Bender, Anne Mette; Kawachi, Ichiro; Jørgensen, Torben; Pisinger, Charlotta

    2015-07-22

    Participation in population-based preventive health check has declined over the past decades. More research is needed to determine factors enhancing participation. The objective of this study was to examine the association between two measures of neighborhood level social capital on participation in the health check phase of a population-based lifestyle intervention. The study population comprised 12,568 residents of 73 Danish neighborhoods in the intervention group of a large population-based lifestyle intervention study - the Inter99. Two measures of social capital were applied; informal socializing and voting turnout. In a multilevel analysis only adjusting for age and sex, a higher level of neighborhood social capital was associated with higher probability of participating in the health check. Inclusion of both individual socioeconomic position and neighborhood deprivation in the model attenuated the coefficients for informal socializing, while voting turnout became non-significant. Higher level of neighborhood social capital was associated with higher probability of participating in the health check phase of a population-based lifestyle intervention. Most of the association between neighborhood social capital and participation in preventive health checks can be explained by differences in individual socioeconomic position and level of neighborhood deprivation. Nonetheless, there seems to be some residual association between social capital and health check participation, suggesting that activating social relations in the community may be an avenue for boosting participation rates in population-based health checks. ClinicalTrials.gov (registration no. NCT00289237 ).

  1. Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.

    PubMed

    Tanskanen, Tomas; van den Berg, Linda; Välimäki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Bexe Lindskog, Elinor; Tõnisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip J; Tuupanen, Sari; Gylfe, Alexandra E; Hänninen, Ulrika A; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti-Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Tim S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Win, Aung K; Hopper, John; Jenkins, Mark A; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fredrick R; Casey, Graham; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Houlston, Richard S; Palin, Kimmo; Aaltonen, Lauri A

    2018-02-01

    Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10 -4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10 -9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations. © 2017 UICC.

  2. Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals.

    PubMed

    Yang, Lijuan; Zhou, Xianghai; Luo, Yingying; Sun, Xiuqin; Tang, Yong; Guo, Wulan; Han, Xueyao; Ji, Linong

    2012-01-01

    A number of studies have been performed to identify the association between potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene and type 2 diabetes mellitus (T2DM) in East Asian populations, with inconsistent results. The main aim of this work was to evaluate more precisely the genetic influence of KCNJ11 on T2DM in East Asian populations by means of a meta-analysis. We identified 20 articles for qualitative analysis and 16 were eligible for quantitative analysis (meta-analysis) by database searching up to May 2010. The association was assessed under different genetic models, and the pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. The allelic and genotypic contrast demonstrated that the association between KCNJ11 and T2DM was significant for rs5210. However, not all results for rs5215 and rs5218 showed significant associations. For rs5219, the combined ORs (95% CIs) for allelic contrast, dominant and recessive models contrast (with allelic frequency and genotypic distribution data) were 1.139 (1.093-1.188), 1.177 (1.099-1.259) and 1.207 (1.094-1.332), respectively (random effect model). The analysis on the most completely adjusted ORs (95% CIs) by the covariates of rs5219 all presented significant associations under different genetic models. Population-stratified analysis (Korean, Japanese and Chinese) and sensitivity analysis verified the significant results. Cumulative meta-analysis including publication time and sample size illustrated the exaggerated genetic effect in the earliest studies. Heterogeneity and publication bias were assessed. Our study verified that single nucleotide polymorphisms (SNPs) of KCNJ11 gene were significantly associated with the risk of T2DM in East Asian populations.

  3. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

    PubMed Central

    Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

    2016-01-01

    Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

  4. Fine-scale patterns of population stratification confound rare variant association tests.

    PubMed

    O'Connor, Timothy D; Kiezun, Adam; Bamshad, Michael; Rich, Stephen S; Smith, Joshua D; Turner, Emily; Leal, Suzanne M; Akey, Joshua M

    2013-01-01

    Advances in next-generation sequencing technology have enabled systematic exploration of the contribution of rare variation to Mendelian and complex diseases. Although it is well known that population stratification can generate spurious associations with common alleles, its impact on rare variant association methods remains poorly understood. Here, we performed exhaustive coalescent simulations with demographic parameters calibrated from exome sequence data to evaluate the performance of nine rare variant association methods in the presence of fine-scale population structure. We find that all methods have an inflated spurious association rate for parameter values that are consistent with levels of differentiation typical of European populations. For example, at a nominal significance level of 5%, some test statistics have a spurious association rate as high as 40%. Finally, we empirically assess the impact of population stratification in a large data set of 4,298 European American exomes. Our results have important implications for the design, analysis, and interpretation of rare variant genome-wide association studies.

  5. Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations

    PubMed Central

    Band, Gavin; Le, Quang Si; Jostins, Luke; Pirinen, Matti; Kivinen, Katja; Jallow, Muminatou; Sisay-Joof, Fatoumatta; Bojang, Kalifa; Pinder, Margaret; Sirugo, Giorgio; Conway, David J.; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Taylor, Terrie; Ndila, Carolyne; Peshu, Norbert; Marsh, Kevin; Williams, Thomas N.; Alcock, Daniel; Andrews, Robert; Edkins, Sarah; Gray, Emma; Hubbart, Christina; Jeffreys, Anna; Rowlands, Kate; Schuldt, Kathrin; Clark, Taane G.; Small, Kerrin S.; Teo, Yik Ying; Kwiatkowski, Dominic P.; Rockett, Kirk A.; Barrett, Jeffrey C.; Spencer, Chris C. A.

    2013-01-01

    Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic diversity, both within and between populations, is far more extensive. We analyse genome-wide data from approximately 5,000 individuals with severe malaria and 7,000 population controls from three different locations in Africa. Our results show that the standard approach is well powered to detect known malaria susceptibility loci when sample sizes are large, and that modern methods for association analysis can control the potential confounding effects of population structure. We show that pattern of association around the haemoglobin S allele differs substantially across populations due to differences in haplotype structure. Motivated by these observations we consider new approaches to association analysis that might prove valuable for multicentre GWAS in Africa: we relax the assumptions of SNP–based fixed effect analysis; we apply Bayesian approaches to allow for heterogeneity in the effect of an allele on risk across studies; and we introduce a region-based test to allow for heterogeneity in the location of causal alleles. PMID:23717212

  6. Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population

    PubMed Central

    de Kovel, Carolien G.; Mulder, Flip; van Setten, Jessica; van ‘t Slot, Ruben; Al-Rubaish, Abdullah; Alshehri, Abdullah M.; Al Faraidy, Khalid; Al-Ali, Abdullah; Al-Madan, Mohammed; Al Aqaili, Issa; Larbi, Emmanuel; Al-Ali, Rudaynah; Alzahrani, Alhusain; Asselbergs, Folkert W.; Koeleman, Bobby P. C.; Al-Ali, Amein

    2016-01-01

    Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h2 = 0.53, S.E. = 0.1, p = 4e-12) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations. PMID:26849363

  7. Quantitative genetic analysis of the body composition and blood pressure association in two ethnically diverse populations.

    PubMed

    Ghosh, Sudipta; Dosaev, Tasbulat; Prakash, Jai; Livshits, Gregory

    2017-04-01

    The major aim of this study was to conduct comparative quantitative-genetic analysis of the body composition (BCP) and somatotype (STP) variation, as well as their correlations with blood pressure (BP) in two ethnically, culturally and geographically different populations: Santhal, indigenous ethnic group from India and Chuvash, indigenous population from Russia. Correspondently two pedigree-based samples were collected from 1,262 Santhal and1,558 Chuvash individuals, respectively. At the first stage of the study, descriptive statistics and a series of univariate regression analyses were calculated. Finally, multiple and multivariate regression (MMR) analyses, with BP measurements as dependent variables and age, sex, BCP and STP as independent variables were carried out in each sample separately. The significant and independent covariates of BP were identified and used for re-examination in pedigree-based variance decomposition analysis. Despite clear and significant differences between the populations in BCP/STP, both Santhal and Chuvash were found to be predominantly mesomorphic irrespective of their sex. According to MMR analyses variation of BP significantly depended on age and mesomorphic component in both samples, and in addition on sex, ectomorphy and fat mass index in Santhal and on fat free mass index in Chuvash samples, respectively. Additive genetic component contributes to a substantial proportion of blood pressure and body composition variance. Variance component analysis in addition to above mentioned results suggests that additive genetic factors influence BP and BCP/STP associations significantly. © 2017 Wiley Periodicals, Inc.

  8. Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

    PubMed Central

    Pirastu, Nicola; Kooyman, Maarten; Traglia, Michela; Robino, Antonietta; Willems, Sara M; Pistis, Giorgio; Amin, Najaf; Sala, Cinzia; Karssen, Lennart C; van Duijn, Cornelia M; Toniolo, Daniela; Gasparini, Paolo

    2015-01-01

    Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P=2.1 × 10−8) between white wine liking and rs9276975:C>T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P=8.3 × 10−6). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general. PMID:25758996

  9. Analysis of multilocus zygotic associations.

    PubMed

    Yang, Rong-Cai

    2002-05-01

    While nonrandom associations between zygotes at different loci (zygotic associations) frequently occur in Hardy-Weinberg disequilibrium populations, statistical analysis of such associations has received little attention. In this article, we describe the joint distributions of zygotes at multiple loci, which are completely characterized by heterozygosities at individual loci and various multilocus zygotic associations. These zygotic associations are defined in the same fashion as the usual multilocus linkage (gametic) disequilibria on the basis of gametic and allelic frequencies. The estimation and test procedures are described with details being given for three loci. The sampling properties of the estimates are examined through Monte Carlo simulation. The estimates of three-locus associations are not free of bias due to the presence of two-locus associations and vice versa. The power of detecting the zygotic associations is small unless different loci are strongly associated and/or sample sizes are large (>100). The analysis of zygotic associations not only offers an effective means of packaging numerous genic disequilibria required for a complete characterization of multilocus structure, but also provides opportunities for making inference about evolutionary and demographic processes through a comparative assessment of zygotic association vs. gametic disequilibrium for the same set of loci in nonequilibrium populations.

  10. TCF7L2 rs7903146 polymorphism and diabetic nephropathy association is not independent of type 2 diabetes--a study in a south Indian population and meta-analysis.

    PubMed

    Hussain, Hajarah; Ramachandran, Vinu; Ravi, Samathmika; Sajan, Teena; Ehambaram, Kiruthiha; Gurramkonda, Venkatesh Babu; Ramanathan, Gnanasambandan; Bhaskar, Lakkakula Venkata

    2014-01-01

    Diabetic nephropathy (DN) is a chronic microangiopathic complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The TCF7L2 gene has been reported to be associated with type 2 diabetes risk. We aimed to investigate the impact of TCF7L2 gene on the susceptibility of T2DM and DN in a south Indian population. Plus to evaluate the association of rs7903146 in the TCF7L2 gene with T2DM in the Indian population. The subjects recruited for this included 55 diabetic cases with diabetic nephropathy, 68 diabetic cases without nephropathy, and 82 non-diabetic healthy controls. Genomic DNA was isolated from blood and genotyping of TCF7L2 rs7903146 was performed by PCR-RFLP analysis. A literature survey was carried out into the effect of rs7903146 on genetic susceptibility to T2DM in Indian populations and we then performed a meta-analysis in order to evaluate its association with T2DM. Analysis of TCF7L2 rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the 'T' allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM. Meta-analysis showed that the mutant allele and genotypes are associated with T2DM in Indian populations. In summary, a significant association exists between the 'T' allele and DN, but this association is not independent of T2DM. Pooled meta-analysis of studies on rs7903146 and T2DM confirmed that rs7903146 is significantly associated with susceptibility to T2DM in Indian populations.

  11. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

    PubMed Central

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R.; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick TH; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S.; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L.; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L.; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z.; Kwon, Soonil; Taylor, Kent D.; Chen, Yii-Der I.; Rotter, Jerome I.; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L.; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E. Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-01-01

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. PMID:24861553

  12. A Genome Wide Association Study Identifies Common Variants Associated with Lipid Levels in the Chinese Population

    PubMed Central

    Wu, Chen; Yang, Handong; Yu, Dianke; Yang, Xiaobo; Zhang, Xiaomin; Wang, Yiqin; Sun, Jielin; Gao, Yong; Tan, Aihua; He, Yunfeng; Zhang, Haiying; Qin, Xue; Zhu, Jingwen; Li, Huaixing; Lin, Xu; Zhu, Jiang; Min, Xinwen; Lang, Mingjian; Li, Dongfeng; Zhai, Kan; Chang, Jiang; Tan, Wen; Yuan, Jing; Chen, Weihong; Wang, Youjie; Wei, Sheng; Miao, Xiaoping; Wang, Feng; Fang, Weimin; Liang, Yuan; Deng, Qifei; Dai, Xiayun; Lin, Dafeng; Huang, Suli; Guo, Huan; Lilly Zheng, S.; Xu, Jianfeng; Lin, Dongxin; Hu, Frank B.; Wu, Tangchun

    2013-01-01

    Plasma lipid levels are important risk factors for cardiovascular disease and are influenced by genetic and environmental factors. Recent genome wide association studies (GWAS) have identified several lipid-associated loci, but these loci have been identified primarily in European populations. In order to identify genetic markers for lipid levels in a Chinese population and analyze the heterogeneity between Europeans and Asians, especially Chinese, we performed a meta-analysis of two genome wide association studies on four common lipid traits including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) in a Han Chinese population totaling 3,451 healthy subjects. Replication was performed in an additional 8,830 subjects of Han Chinese ethnicity. We replicated eight loci associated with lipid levels previously reported in a European population. The loci genome wide significantly associated with TC were near DOCK7, HMGCR and ABO; those genome wide significantly associated with TG were near APOA1/C3/A4/A5 and LPL; those genome wide significantly associated with LDL were near HMGCR, ABO and TOMM40; and those genome wide significantly associated with HDL were near LPL, LIPC and CETP. In addition, an additive genotype score of eight SNPs representing the eight loci that were found to be associated with lipid levels was associated with higher TC, TG and LDL levels (P = 5.52×10-16, 1.38×10-6 and 5.59×10-9, respectively). These findings suggest the cumulative effects of multiple genetic loci on plasma lipid levels. Comparisons with previous GWAS of lipids highlight heterogeneity in allele frequency and in effect size for some loci between Chinese and European populations. The results from our GWAS provided comprehensive and convincing evidence of the genetic determinants of plasma lipid levels in a Chinese population. PMID:24386095

  13. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

    PubMed

    Wen, Wanqing; Zheng, Wei; Okada, Yukinori; Takeuchi, Fumihiko; Tabara, Yasuharu; Hwang, Joo-Yeon; Dorajoo, Rajkumar; Li, Huaixing; Tsai, Fuu-Jen; Yang, Xiaobo; He, Jiang; Wu, Ying; He, Meian; Zhang, Yi; Liang, Jun; Guo, Xiuqing; Sheu, Wayne Huey-Herng; Delahanty, Ryan; Guo, Xingyi; Kubo, Michiaki; Yamamoto, Ken; Ohkubo, Takayoshi; Go, Min Jin; Liu, Jian Jun; Gan, Wei; Chen, Ching-Chu; Gao, Yong; Li, Shengxu; Lee, Nanette R; Wu, Chen; Zhou, Xueya; Song, Huaidong; Yao, Jie; Lee, I-Te; Long, Jirong; Tsunoda, Tatsuhiko; Akiyama, Koichi; Takashima, Naoyuki; Cho, Yoon Shin; Ong, Rick Th; Lu, Ling; Chen, Chien-Hsiun; Tan, Aihua; Rice, Treva K; Adair, Linda S; Gui, Lixuan; Allison, Matthew; Lee, Wen-Jane; Cai, Qiuyin; Isomura, Minoru; Umemura, Satoshi; Kim, Young Jin; Seielstad, Mark; Hixson, James; Xiang, Yong-Bing; Isono, Masato; Kim, Bong-Jo; Sim, Xueling; Lu, Wei; Nabika, Toru; Lee, Juyoung; Lim, Wei-Yen; Gao, Yu-Tang; Takayanagi, Ryoichi; Kang, Dae-Hee; Wong, Tien Yin; Hsiung, Chao Agnes; Wu, I-Chien; Juang, Jyh-Ming Jimmy; Shi, Jiajun; Choi, Bo Youl; Aung, Tin; Hu, Frank; Kim, Mi Kyung; Lim, Wei Yen; Wang, Tzung-Dao; Shin, Min-Ho; Lee, Jeannette; Ji, Bu-Tian; Lee, Young-Hoon; Young, Terri L; Shin, Dong Hoon; Chun, Byung-Yeol; Cho, Myeong-Chan; Han, Bok-Ghee; Hwu, Chii-Min; Assimes, Themistocles L; Absher, Devin; Yan, Xiaofei; Kim, Eric; Kuo, Jane Z; Kwon, Soonil; Taylor, Kent D; Chen, Yii-Der I; Rotter, Jerome I; Qi, Lu; Zhu, Dingliang; Wu, Tangchun; Mohlke, Karen L; Gu, Dongfeng; Mo, Zengnan; Wu, Jer-Yuarn; Lin, Xu; Miki, Tetsuro; Tai, E Shyong; Lee, Jong-Young; Kato, Norihiro; Shu, Xiao-Ou; Tanaka, Toshihiro

    2014-10-15

    Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Variables associated with olfactory disorders in adults: A U.S. population-based analysis.

    PubMed

    Noel, Julia; Habib, Al-Rahim R; Thamboo, Andrew; Patel, Zara M

    2017-03-01

    Olfactory dysfunction is known to have significant social, psychological, and safety implications. Despite increasingly recognized prevalence, potential risk factors for olfactory loss have been arbitrarily documented and knowledge is limited in scale. The aim of this study is to identify potential demographic and exposure variables correlating with olfactory dysfunction. Cross-sectional analysis of the 2011-2012 and 2013-2014 editions of the National Health Examination and Nutrition Survey was performed. The utilized survey reports from a nationally representative sample of about 5000 persons each year located in counties across the United States. There is an interview and physical examination component which includes demographic, socioeconomic, dietary, and health-related questions as well as medical, dental, physiologic measurements, and laboratory tests. 3594 adult respondents from 2011 to 2012 and 3708 respondents from 2013 to 2014 were identified from the above population-based database. The frequency of self-reported disorders as well as performance on odor identification testing was determined in relation to demographic factors, occupational or environmental exposures, and urinary levels of environmental and industrial compounds. In both subjective and objective analysis, smell disorders were significantly more common with increasing age. While the non-Hispanic Black and non-Hispanic Asian populations were less likely to report subjective olfactory loss, they, along with Hispanics, performed more poorly on odor identification than Caucasians. Those with limited education had a decreased prevalence of hyposmia. Women outperformed men on smell testing. Those reporting exposure to vapors were more likely to experience olfactory dysfunction, and urinary levels of manganese, 2-Thioxothiazolidine-4-carboxylic acid, and 2-Aminothiazoline-4-carboxylic acid were lower among respondents with subjective smell disturbance. In odor detection, elevated serum levels of

  15. Association between salt and hypertension in rural and urban populations of low to middle income countries: a systematic review and meta-analysis of population based studies.

    PubMed

    Subasinghe, Asvini K; Arabshahi, Simin; Busingye, Doreen; Evans, Roger G; Walker, Karen Z; Riddell, Michaela A; Thrift, Amanda G

    2016-01-01

    The prevalence of hypertension, the greatest contributor to mortality globally, is increasing in low-and-middle income countries (LMICs). In urban regions of LMICs, excessive salt intake is associated with increased risk of hypertension. We aimed to determine whether this is the case in rural regions as well. We performed a meta-analysis of studies in rural and urban areas of LMICs in which the association of salt and hypertension were assessed using multivariable models. We identified 18 studies with a total of 134,916 participants. The prevalence of high salt intake ranged from 21.3% to 89.5% in rural and urban populations. When salt was analysed as a continuous variable, a greater impact of salt on hypertension was found in urban (n=4) (pooled effect size (ES) 1.42, 95% CI 1.19, 1.69) than in rural populations (n=4) (pooled ES 1.07, 95% CI 1.04, 1.10, p for difference <0.001). In studies where salt was analysed continuously, a greater impact of salt on hypertension was observed in lean rural populations (BMI <23 kg/m2) than in non-lean rural populations (BMI >=23 kg/m2, p for difference <0.001). The prevalence of high salt intake is similar in rural and urban regions. Excessive salt intake has a greater impact on the prevalence of hypertension in urban than rural regions. BMI appears to modify the relationship between salt and hypertension in rural populations.

  16. Factors Associated with Gastrointestinal Parasitic Infections among Young Population in Northeast Brazil.

    PubMed

    da Silva, Juliana Vasconcelos Lyra; Fontes, Gilberto; Dos Santos, Célia Dias; Dos Santos, Rafael Vital; da Rocha, Eliana Maria Mauricio

    2016-01-01

    Background. Intestinal parasitic infections constitute a major public health problem that is frequently associated with poverty, inadequate sanitation, and the nutritional status of the population. Objective. The aim of the present study is to investigate the possible association of parasitic infections, sanitary conditions, hygiene practices, and the nutritional and socioeconomic status of a poor youth population. Methods. A cross-sectional study was conducted with 367 children and adolescents inhabiting a substandard settlement in the urban area of Maceió (Alagoas State, Brazil). Data collection included socioeconomic status, anthropometric measurements, fecal sample examinations, and laboratory blood analysis. The identification of factors associated with gastrointestinal parasitic infections was undertaken through bi- and multivariate analyses. Results. Stool sample analysis obtained from 300 individuals revealed that 204 (68%) were infected with at least one parasite species and of these 130 (63.7%) were polyparasitized. No significant associations were identified between low height for age (stunted), parasitic infections, and polyparasitism. There was also no association between family income and parasitosis. However, low socioeconomic status proved to be a potential risk factor for parasitic infections. Conclusion. Actions must be taken to improve sanitation, housing, and environmental conditions in order to eliminate the risk factors for parasitic infections, and thereby guarantee a better quality of life for this population.

  17. Association between PAI-1 4G/5G polymorphism and diabetic nephropathy: a meta-analysis in the Chinese population.

    PubMed

    Gao, Wen-Feng; Guo, Ying-Bo; Bai, Yu; Ding, Xin-Yu; Yan, Yong-Ji; Wu, Zhen-Qi

    2016-09-01

    Although a number of studies have been conducted on the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and diabetic nephropathy (DN) in Chinese population, this association remains elusive and controversial. To further assess the effects of PAI-1 4G/5G polymorphism on the risk of DN, a meta-analysis was performed in the Chinese population. Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through November, 2015. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. This meta-analysis identified nine studies, including 777 DN cases, 413 healthy controls, and 523 DM controls. In the total analyses, a significantly elevated risk of DN was associated with variants of PAI-1 4G/5G when compared with the healthy group (4G vs. 5G, OR 2.46, 95 % CI 1.45-4.16; 4G/4G vs. 5G/5G, OR 4.32, 95 % CI 1.79-10.39; 4G/4G vs. 4G/5G +5G/5G, OR 2.96, 95 % CI 1.59-5.53; 4G/4G +4G/5G vs. 5G/5G, OR 2.78, 95 % CI 1.34-5.75) and DM group (4G vs. 5G, OR 1.93, 95 % CI 1.28-2.92; 4G/4G vs. 5G/5G, OR 2.99, 95 % CI 1.44-6.21; 4G/4G vs. 4G/5G +5G/5G, OR 2.84, 95 % CI 1.77-4.54). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. This meta-analysis showed that the PAI-1 4G/4G variant, 4G allele might be risk alleles for DN susceptibility in the Chinese population, and further studies in other ethic groups are required for definite conclusions.

  18. Association of rs662799 in APOA5 with CAD in Chinese Han population.

    PubMed

    Chen, Hua; Ding, Shifang; Zhou, Mi; Wu, Xiayin; Liu, Xi; Wu, Yun; Liu, Dechao

    2018-01-08

    CAD (Coronary Artery Disease) is a complex disease that influenced by various environmental and genetic factors. Previous studies have found many single nucleotide polymorphisms (SNPs) associated with the risk of CAD occurrence. However, the results are inconsistent. In this study, we aim to investigate genetic etiology in Chinese Han population by analysis of 7 SNPs in lipid metabolism pathway that previously has been reported to be associated with CAD. A total of 631 samples were used in this study, including 435 CAD cases and 196 normal healthy controls. SNP genotyping were conducted via multiplex PCR amplifying followed by NGS (next-generation sequencing). Rs662799 in APOA5 (Apolipoprotein A5) gene was associated with CAD in Chinese Han population (Odds-ratio = 1.374, P-value = 0.03). No significant association was observed between the rest of SNPs and CAD. Stratified association analysis revealed rs5882 was associated with CAD in non-hypertension group (Odds-ratio = 1.593, P-value = 0.023). Rs1800588 was associated with CAD in smoking group (Odds-ratio = 1.603, P-value = 0.035). The minor allele of rs662799 was the risk factor of CAD occurrences in Chinese Han population.

  19. Sex is a moderator of the association between NOS1AP sequence variants and QTc in two long QT syndrome founder populations: a pedigree-based measured genotype association analysis.

    PubMed

    Winbo, Annika; Stattin, Eva-Lena; Westin, Ida Maria; Norberg, Anna; Persson, Johan; Jensen, Steen M; Rydberg, Annika

    2017-07-18

    Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1AP sequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations. This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs. A substantial variance in mean QTc was seen in genotype positives 476 ± 36 ms (Y111C 483 ± 34 ms; R518* 462 ± 34 ms) and genotype negatives 433 ± 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p < 0.001). In a multivariable analysis including the entire study population and adjusted for KCNQ1 genotype, sex and age, NOS1AP sequence variants rs12143842 and rs16847548 (but not rs4657139) were significantly associated with QT prolongation, +18 ms (p = 0.0007) and +17 ms (p = 0.006), respectively. Significant sex-interactions were detected for both sequent variants (interaction term r = 0.892, p < 0.001 and r = 0.944, p < 0.001, respectively). Notably, across the genotype groups, when stratified by sex neither rs12143842 nor rs16847548 were significantly associated with

  20. Association Analysis in Rice: From Application to Utilization

    PubMed Central

    Zhang, Peng; Zhong, Kaizhen; Shahid, Muhammad Qasim; Tong, Hanhua

    2016-01-01

    Association analysis based on linkage disequilibrium (LD) is an efficient way to dissect complex traits and to identify gene functions in rice. Although association analysis is an effective way to construct fine maps for quantitative traits, there are a few issues which need to be addressed. In this review, we will first summarize type, structure, and LD level of populations used for association analysis of rice, and then discuss the genotyping methods and statistical approaches used for association analysis in rice. Moreover, we will review current shortcomings and benefits of association analysis as well as specific types of future research to overcome these shortcomings. Furthermore, we will analyze the reasons for the underutilization of the results within association analysis in rice breeding. PMID:27582745

  1. Association between childhood eczema and headaches: An analysis of 19 US population-based studies.

    PubMed

    Silverberg, Jonathan I

    2016-02-01

    Atopic dermatitis (or eczema) is a chronic inflammatory disorder associated with sleep disturbances and quality-of-life impairment. Sleep disturbances have been shown to cause headaches in childhood. However, an association between eczema and headaches is not well established. We sought to determine whether childhood eczema is associated with increased headaches and whether such association is related to fatigue or sleep disturbance. We analyzed data from 401,002 children and adolescents in 19 US population-based cross-sectional studies from the National Survey of Children's Health 2003/2004 and 2007/2008 and the National Health Interview Survey 1997-2013. In multivariate models controlling for age, sex, race/ethnicity, household income, highest level of education in the family, insurance coverage, number of persons in the household, birthplace in the United States, ever history of asthma, hay fever, and food allergy, eczema was found to be associated with headaches in 14 of 19 studies. In a pooled analysis of all 19 studies, children with eczema compared with those without eczema had a significantly higher prevalence (10.7% [95% CI, 10.3% to 11.0%] vs 5.4% [95% CI, 5.3% to 5.5%]) and odds (1.52 [95% CI, 1.45-1.59]) of headaches. Mild (1.79 [95% CI, 1.07-2.98]) and severe (2.72 [95% CI, 1.33-5.57]) eczema were associated with significantly higher odds of headaches. In particular, eczema associated with atopy, fatigue, excessive daytime sleepiness, insomnia, and only 0 to 3 nights of sufficient sleep had even higher odds of headache than eczema alone. Eczema is associated with increased headaches in childhood, particularly in patients with severe disease accompanied by atopy, fatigue, and sleep disturbances. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Association between childhood eczema and headaches: An analysis of 19 US population-based studies

    PubMed Central

    Silverberg, Jonathan I.

    2016-01-01

    Background Atopic dermatitis (or eczema) is a chronic inflammatory disorder associated with sleep disturbances and quality-of-life impairment. Sleep disturbances have been shown to cause headaches in childhood. However, an association between eczema and headaches is not well established. Objectives We sought to determine whether childhood eczema is associated with increased headaches and whether such association is related to fatigue or sleep disturbance. Methods We analyzed data from 401,002 children and adolescents in 19 US population-based cross-sectional studies from the National Survey of Children’s Health 2003/2004 and 2007/2008 and the National Health Interview Survey 1997–2013. Results In multivariate models controlling for age, sex, race/ethnicity, household income, highest level of education in the family, insurance coverage, number of persons in the household, birthplace in the United States, ever history of asthma, hay fever, and food allergy, eczema was found to be associated with headaches in 14 of 19 studies. In a pooled analysis of all 19 studies, children with eczema compared with those without eczema had a significantly higher prevalence (10.7% [95% CI, 10.3% to 11.0%] vs 5.4% [95% CI, 5.3% to 5.5%]) and odds (1.52 [95% CI, 1.45–1.59]) of headaches. Mild (1.79 [95% CI, 1.07–2.98]) and severe (2.72 [95% CI, 1.33–5.57]) eczema were associated with significantly higher odds of headaches. In particular, eczema associated with atopy, fatigue, excessive daytime sleepiness, insomnia, and only 0 to 3 nights of sufficient sleep had even higher odds of headache than eczema alone. Conclusions Eczema is associated with increased headaches in childhood, particularly in patients with severe disease accompanied by atopy, fatigue, and sleep disturbances. PMID:26329510

  3. A serotonin transporter gene (SLC6A4) polymorphism is associated with reduced risk of irritable bowel syndrome in American and Asian population: a meta-analysis.

    PubMed

    Areeshi, Mohammed Y; Haque, Shafiul; Panda, Aditya K; Mandal, Raju K

    2013-01-01

    Association studies of serotonin transporter gene SLC6A4 I/S polymorphism and irritable bowel syndrome (IBS) have shown inconsistent and contradictory results among different populations. In the present study, meta-analysis was performed to evaluate the association between SLC6A4 I/S polymorphism and IBS susceptibility. Systemic assessment was performed for the published studies based on the association of SLC6A4 I/S polymorphism and IBS risk from PubMed (Medline), EMBASE search. A meta-analysis was done to appraise the said association. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of twelve studies comprising 2068 IBS cases and 2076 controls were included in this meta-analysis. Overall, no significant results were obtained for S allele carrier (S vs. I: p=0.488; OR=1.073, 95% CI=0.879 to 1.311) Co-dominant (SS vs. II; p=0.587; OR=1.112, 95% CI=0.758 to 1.631), (IS vs. II; p=0.361; OR=0.878, 95% CI=0.665 to 1.160). Similarly, dominant (SS+IS vs. II: p=0.853; OR=0.974, 95% CI=0.736 to 1.288) and recessive (SS vs. II+IS: p=0.267; OR=1.172, 95% CI=0.886 to 1.522) genetic models did not demonstrate risk. In the subgroup population based analysis, reduced risks were found in American (IS vs. II: p=0.009; OR=0.685, 95% CI=0.516 to 0.908) and Asian (SS+IS vs. II; p=0.001; OR=0.116, 95% CI=0.068 to 0.197) population. However, no risk was observed in European population. This investigation clearly demonstrates that SLC6A4 (Ins/Del) polymorphism is associated with reduced risk of IBS in American and Asian population. However, future well-designed studies with stratified case control and biological characterization will be needed to validate this finding.

  4. Associations of all-cause mortality with census-based neighbourhood deprivation and population density in Japan: a multilevel survival analysis.

    PubMed

    Nakaya, Tomoki; Honjo, Kaori; Hanibuchi, Tomoya; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2014-01-01

    Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455), consisting of middle-aged residents (40 to 59 years at the baseline in 1990) living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs) of all-cause mortality by two census-based areal variables--areal deprivation index and population density--as well as individualistic variables such as socioeconomic status and various risk factors. We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables) significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely populated and highly deprived neighbourhoods.

  5. Associations of All-Cause Mortality with Census-Based Neighbourhood Deprivation and Population Density in Japan: A Multilevel Survival Analysis

    PubMed Central

    Nakaya, Tomoki; Honjo, Kaori; Hanibuchi, Tomoya; Ikeda, Ai; Iso, Hiroyasu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2014-01-01

    Background Despite evidence that neighbourhood conditions affect residents' health, no prospective studies of the association between neighbourhood socio-demographic factors and all-cause mortality have been conducted in non-Western societies. Thus, we examined the effects of areal deprivation and population density on all-cause mortality in Japan. Methods We employed census and survival data from the Japan Public Health Center-based Prospective Study, Cohort I (n = 37,455), consisting of middle-aged residents (40 to 59 years at the baseline in 1990) living in four public health centre districts. Data spanned between 1990 and 2010. A multilevel parametric proportional-hazard regression model was applied to estimate the hazard ratios (HRs) of all-cause mortality by two census-based areal variables —areal deprivation index and population density—as well as individualistic variables such as socioeconomic status and various risk factors. Results We found that areal deprivation and population density had moderate associations with all-cause mortality at the neighbourhood level based on the survival data with 21 years of follow-ups. Even when controlling for individualistic socio-economic status and behavioural factors, the HRs of the two areal factors (using quartile categorical variables) significantly predicted mortality. Further, this analysis indicated an interaction effect of the two factors: areal deprivation prominently affects the health of residents in neighbourhoods with high population density. Conclusions We confirmed that neighbourhood socio-demographic factors are significant predictors of all-cause death in Japanese non-metropolitan settings. Although further study is needed to clarify the cause-effect relationship of this association, the present findings suggest that health promotion policies should consider health disparities between neighbourhoods and possibly direct interventions towards reducing mortality in densely populated and highly

  6. The CLU gene rs11136000 variant is significantly associated with Alzheimer's disease in Caucasian and Asian populations.

    PubMed

    Liu, Guiyou; Wang, Haiyang; Liu, Jiafeng; Li, Jingbo; Li, Hali; Ma, Guoda; Jiang, Yongshuai; Chen, Zugen; Zhao, Bin; Li, Keshen

    2014-03-01

    Large-scale genomewide association studies have reported that the CLU rs11136000 polymorphism is significantly associated with Alzheimer's disease (AD) in people of Caucasian ancestry. Recently, this association was investigated in Asian populations (Chinese, Japanese, and Korean). However, these studies reported either a weak association or no association between the rs11136000 polymorphism and AD. We believe that this discrepancy may be caused by the relatively small sample size of the previous studies and the genetic heterogeneity of the rs11136000 polymorphism in AD among different populations. For this study, we searched the PubMed and AlzGene databases. We selected 18 independent studies (6 studies of Asian populations and 12 of populations of Caucasian ancestry) that evaluated the association between the rs11136000 polymorphism and AD using a case-control experimental design. We evaluated the genetic heterogeneity of the rs11136000 polymorphism in Caucasian and Asian populations. We then investigated the rs11136000 polymorphism by a meta-analysis in Asian populations using allele, dominant, and recessive models. We identified a significant association between rs11136000 and AD with the allele model (P = 2.00 × 10(-4)) and the dominant model (P = 5.00 × 10(-3)). Meanwhile, a similar genetic risk of the rs11136000 polymorphism in AD was observed in Asian and Caucasian populations. Further meta-analysis in pooled Asian and Caucasian populations indicated a more significant association with the allele (P = 8.30 × 10(-24)), dominant (P = 4.46 × 10(-17)), and recessive (P = 3.92 × 10(-12)) models. Collectively, our findings from this meta-analysis indicate that the effect of the CLU rs11136000 polymorphism on AD risk in Asian cohorts (Chinese, Japanese, and Korean) is consistent with the protective effect observed in Caucasian AD cohorts.

  7. Population-specific association of genes for telomere-associated proteins with longevity in an Italian population.

    PubMed

    Crocco, Paolina; Barale, Roberto; Rose, Giuseppina; Rizzato, Cosmeri; Santoro, Aurelia; De Rango, Francesco; Carrai, Maura; Fogar, Paola; Monti, Daniela; Biondi, Fiammetta; Bucci, Laura; Ostan, Rita; Tallaro, Federica; Montesanto, Alberto; Zambon, Carlo-Federico; Franceschi, Claudio; Canzian, Federico; Passarino, Giuseppe; Campa, Daniele

    2015-06-01

    Leukocyte telomere length (LTL) has been observed to be hereditable and correlated with longevity. However, contrasting results have been reported in different populations on the value of LTL heritability and on how biology of telomeres influences longevity. We investigated whether the variability of genes correlated to telomere maintenance is associated with telomere length and affects longevity in a population from Southern Italy (20-106 years). For this purpose we analyzed thirty-one polymorphisms in eight telomerase-associated genes of which twelve in the genes coding for the core enzyme (TERT and TERC) and the remaining in genes coding for components of the telomerase complex (TERF1, TERF2, TERF2IP, TNKS, TNKS2 and TEP1). We did not observe (after correcting for multiple testing) statistically significant associations between SNPs and LTL, possibly suggesting a low genetic influence of the variability of these genes on LTL in the elderly. On the other hand, we found that the variability of genes encoding for TERF1 and TNKS2, not directly involved in LTL, but important for keeping the integrity of the structure, shows a significant association with longevity. This suggests that the maintenance of these chromosomal structures may be critically important for preventing, or delaying, senescence and aging. Such a correlation was not observed in a population from northern Italy that we used as an independent replication set. This discrepancy is in line with previous reports regarding both the population specificity of results on telomere biology and the differences of aging in northern and southern Italy.

  8. 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.

  9. Iraqi Population Displacement Analysis

    DTIC Science & Technology

    2016-11-01

    CENTER FOR ARMY ANALYSIS 6001 GOETHALS ROAD FORT BELVOIR, VA 22060-5230 CAA-2015098 IRAQI POPULATION DISPLACEMENT ANALYSIS NOVEMBER 2016...CONTRACT NUMBER Iraqi Population Displacement Analysis PDMC 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ms...NOTES 14. ABSTRACT The purpose of this study was to inform CJ34 Civil Military Operations decisions on placement of internally displaced person (IDP

  10. Association of workplace and population characteristics with prevalence of hypertension among Brazilian industry workers: a multilevel analysis

    PubMed Central

    Vinholes, Daniele B; Bassanesi, Sérgio L; Chaves Junior, Hilton de Castro; Machado, Carlos Alberto; Melo, Ione M F; Fuchs, Flavio Danni

    2017-01-01

    Background Exposure to risk factors for hypertension may be influenced by the characteristics of the workplace, where workers spend most of their daily time. Objectives To evaluate the association between features of the companies, particularly the presence of facilities to provide meals, and of population characteristics and the prevalence of hypertension, taking into account individual risk factors for hypertension. Material and methods This multilevel analysis was based on a cross-sectional study with individual and company data from the SESI (Serviço Social da Indústria–Social Service of Industries) study and population-based data from the national census statistics. Workers aged ≥15 years were randomly selected from small (20–99), medium (100–499) and large (≥500 employees) companies per state using multistage sampling. Logistic regression was used to analyse the association between hypertension and individual, workplace and population variables, with odds ratios (ORs; 95% CI) adjusted for three-level variables. Results 4818 Workers from 157 companies were interviewed and their blood pressure, weight and height were measured. Overall, 77% were men, aged 35.4 ±10.7 years, with 8.7 ±4.1 years of schooling and mostly worked in companies with a staff canteen (66%). Besides individual characteristics—being male, ageing, low schooling, alcohol abuse and higher BMI—a workplace with no staff canteen (OR=1.28; 95% CI 1.08 to 1.52), small companies (OR=1.31; 95% CI 1.07 to 1.60) and living in cities with higher economic inequality (OR=1.47; 95% CI 1.23 to 1.76) were associated with a higher risk for hypertension. Conclusion Among Brazilian workers, the prevalence of hypertension is associated with individual risk factors, lack of a canteen at the workplace, small companies and higher economic inequalities of cities. These three-level characteristics help to interpret differences in the prevalence of hypertension between regions or countries

  11. Association of workplace and population characteristics with prevalence of hypertension among Brazilian industry workers: a multilevel analysis.

    PubMed

    Vinholes, Daniele B; Bassanesi, Sérgio L; Chaves Junior, Hilton de Castro; Machado, Carlos Alberto; Melo, Ione M F; Fuchs, Flavio Danni; Fuchs, Sandra Costa

    2017-08-21

    Exposure to risk factors for hypertension may be influenced by the characteristics of the workplace, where workers spend most of their daily time. To evaluate the association between features of the companies, particularly the presence of facilities to provide meals, and of population characteristics and the prevalence of hypertension, taking into account individual risk factors for hypertension. This multilevel analysis was based on a cross-sectional study with individual and company data from the SESI (Serviço Social da Indústria-Social Service of Industries) study and population-based data from the national census statistics. Workers aged ≥15 years were randomly selected from small (20-99), medium (100-499) and large (≥500 employees) companies per state using multistage sampling. Logistic regression was used to analyse the association between hypertension and individual, workplace and population variables, with odds ratios (ORs; 95% CI) adjusted for three-level variables. 4818 Workers from 157 companies were interviewed and their blood pressure, weight and height were measured. Overall, 77% were men, aged 35.4 ±10.7 years, with 8.7 ±4.1 years of schooling and mostly worked in companies with a staff canteen (66%). Besides individual characteristics-being male, ageing, low schooling, alcohol abuse and higher BMI-a workplace with no staff canteen (OR=1.28; 95% CI 1.08 to 1.52), small companies (OR=1.31; 95% CI 1.07 to 1.60) and living in cities with higher economic inequality (OR=1.47; 95% CI 1.23 to 1.76) were associated with a higher risk for hypertension. Among Brazilian workers, the prevalence of hypertension is associated with individual risk factors, lack of a canteen at the workplace, small companies and higher economic inequalities of cities. These three-level characteristics help to interpret differences in the prevalence of hypertension between regions or countries. © Article author(s) (or their employer(s) unless otherwise stated in the

  12. Mapping asthma-associated variants in admixed populations

    PubMed Central

    Mersha, Tesfaye B.

    2015-01-01

    Admixed populations arise when two or more previously isolated populations interbreed. Mapping asthma susceptibility loci in an admixed population using admixture mapping (AM) involves screening the genome of individuals of mixed ancestry for chromosomal regions that have a higher frequency of alleles from a parental population with higher asthma risk as compared with parental population with lower asthma risk. AM takes advantage of the admixture created in populations of mixed ancestry to identify genomic regions where an association exists between genetic ancestry and asthma (in contrast to between the genotype of the marker and asthma). The theory behind AM is that chromosomal segments of affected individuals contain a significantly higher-than-average proportion of alleles from the high-risk parental population and thus are more likely to harbor disease–associated loci. Criteria to evaluate the applicability of AM as a gene mapping approach include: (1) the prevalence of the disease differences in ancestral populations from which the admixed population was formed; (2) a measurable difference in disease-causing alleles between the parental populations; (3) reduced linkage disequilibrium (LD) between unlinked loci across chromosomes and strong LD between neighboring loci; (4) a set of markers with noticeable allele-frequency differences between parental populations that contributes to the admixed population (single nucleotide polymorphisms (SNPs) are the markers of choice because they are abundant, stable, relatively cheap to genotype, and informative with regard to the LD structure of chromosomal segments); and (5) there is an understanding of the extent of segmental chromosomal admixtures and their interactions with environmental factors. Although genome-wide association studies have contributed greatly to our understanding of the genetic components of asthma, the large and increasing degree of admixture in populations across the world create many challenges

  13. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.

    PubMed

    Wu, Chen; Wang, Zhaoming; Song, Xin; Feng, Xiao-Shan; Abnet, Christian C; He, Jie; Hu, Nan; Zuo, Xian-Bo; Tan, Wen; Zhan, Qimin; Hu, Zhibin; He, Zhonghu; Jia, Weihua; Zhou, Yifeng; Yu, Kai; Shu, Xiao-Ou; Yuan, Jian-Min; Zheng, Wei; Zhao, Xue-Ke; Gao, She-Gan; Yuan, Zhi-Qing; Zhou, Fu-You; Fan, Zong-Min; Cui, Ji-Li; Lin, Hong-Li; Han, Xue-Na; Li, Bei; Chen, Xi; Dawsey, Sanford M; Liao, Linda; Lee, Maxwell P; Ding, Ti; Qiao, You-Lin; Liu, Zhihua; Liu, Yu; Yu, Dianke; Chang, Jiang; Wei, Lixuan; Gao, Yu-Tang; Koh, Woon-Puay; Xiang, Yong-Bing; Tang, Ze-Zhong; Fan, Jin-Hu; Han, Jing-Jing; Zhou, Sheng-Li; Zhang, Peng; Zhang, Dong-Yun; Yuan, Yuan; Huang, Ying; Liu, Chunling; Zhai, Kan; Qiao, Yan; Jin, Guangfu; Guo, Chuanhai; Fu, Jianhua; Miao, Xiaoping; Lu, Changdong; Yang, Haijun; Wang, Chaoyu; Wheeler, William A; Gail, Mitchell; Yeager, Meredith; Yuenger, Jeff; Guo, Er-Tao; Li, Ai-Li; Zhang, Wei; Li, Xue-Min; Sun, Liang-Dan; Ma, Bao-Gen; Li, Yan; Tang, Sa; Peng, Xiu-Qing; Liu, Jing; Hutchinson, Amy; Jacobs, Kevin; Giffen, Carol; Burdette, Laurie; Fraumeni, Joseph F; Shen, Hongbing; Ke, Yang; Zeng, Yixin; Wu, Tangchun; Kraft, Peter; Chung, Charles C; Tucker, Margaret A; Hou, Zhi-Chao; Liu, Ya-Li; Hu, Yan-Long; Liu, Yu; Wang, Li; Yuan, Guo; Chen, Li-Sha; Liu, Xiao; Ma, Teng; Meng, Hui; Sun, Li; Li, Xin-Min; Li, Xiu-Min; Ku, Jian-Wei; Zhou, Ying-Fa; Yang, Liu-Qin; Wang, Zhou; Li, Yin; Qige, Qirenwang; Yang, Wen-Jun; Lei, Guang-Yan; Chen, Long-Qi; Li, En-Min; Yuan, Ling; Yue, Wen-Bin; Wang, Ran; Wang, Lu-Wen; Fan, Xue-Ping; Zhu, Fang-Heng; Zhao, Wei-Xing; Mao, Yi-Min; Zhang, Mei; Xing, Guo-Lan; Li, Ji-Lin; Han, Min; Ren, Jing-Li; Liu, Bin; Ren, Shu-Wei; Kong, Qing-Peng; Li, Feng; Sheyhidin, Ilyar; Wei, Wu; Zhang, Yan-Rui; Feng, Chang-Wei; Wang, Jin; Yang, Yu-Hua; Hao, Hong-Zhang; Bao, Qi-De; Liu, Bao-Chi; Wu, Ai-Qun; Xie, Dong; Yang, Wan-Cai; Wang, Liang; Zhao, Xiao-Hang; Chen, Shu-Qing; Hong, Jun-Yan; Zhang, Xue-Jun; Freedman, Neal D; Goldstein, Alisa M; Lin, Dongxin; Taylor, Philip R; Wang, Li-Dong; Chanock, Stephen J

    2014-09-01

    We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.

  14. The Role of Local Ancestry Adjustment in Association Studies Using Admixed Populations

    PubMed Central

    Zhang, Jianqi; Stram, Daniel O.

    2016-01-01

    Association analysis using admixed populations imposes challenges and opportunities for disease mapping. By developing some explicit results for the variance of an allele of interest conditional on either local or global ancestry and by simulation of recently admixed genomes we evaluate power and false-positive rates under a variety of scenarios concerning linkage disequilibrium (LD) and the presence of unmeasured variants. Pairwise LD patterns were compared between admixed and nonadmixed populations using the HapMap phase 3 data. Based on the above, we showed that as follows: For causal variants with similar effect size in all populations, power is generally higher in a study using admixed population than using nonadmixed population, especially for highly differentiated SNPs. This gain of power is achieved with adjustment of global ancestry, which completely removes any cross-chromosome inflation of type I error rates, and addresses much of the intrachromosome inflation.If reliably estimated, adjusting for local ancestry precisely recovers the localization that could have been achieved in a stratified analysis of source populations. Improved localization is most evident for highly differentiated SNPs; however, the advantage of higher power is lost on exactly the same differentiated SNPs.In the real admixed populations such as African Americans and Latinos, the expansion of LD is not as dramatic as in our simulation.While adjustment for global ancestry is required prior to announcing a novel association seen in an admixed population, local ancestry adjustment may best be regarded as a localization tool not strictly required for discovery purposes. PMID:25043967

  15. PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

    PubMed Central

    Purcell, Shaun ; Neale, Benjamin ; Todd-Brown, Kathe ; Thomas, Lori ; Ferreira, Manuel A. R. ; Bender, David ; Maller, Julian ; Sklar, Pamela ; de Bakker, Paul I. W. ; Daly, Mark J. ; Sham, Pak C. 

    2007-01-01

    Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis. PMID:17701901

  16. Host Plant-Associated Population Variation in the Carob Moth Ectomyelois ceratoniae in Iran: A Geometric Morphometric Analysis Suggests a Nutritional Basis.

    PubMed Central

    Mozaffarian, Fariba; Sarafrazi, Alimorad; Ganbalani, Gadir Nouri

    2007-01-01

    The carob moth, Ectomyelois ceratoniae (Zeller, 1839) (Lepidoptera: Pyralidae), is the most important pest of pomegranate in Iran. As it has been rarely recorded on other host plants, control methods have mostly been focused on its populations on pomegranate. In this study, shapes and sizes of wings were compared in populations on 4 host plants (pomegranate, fig, pistachio and walnut) using a landmark-based geometric morphometric method, and analysis of partial warp scores and centroid sizes. The results showed significantly smaller wing size in populations on pomegranate and a significant host plant-associated shape difference among populations as a consequence of allometric growth. This suggests that the wing size and shape differences among test populations may not have a genetic basis and could happen because of differences in the nutritional content of host plants. The results of the analysis suggest that the female carob moth lays her eggs on host plants that provide suitable conditions for hatching. The larger size of moths on hosts other than pomegranate showed that some host plants such as fig, pistachio and walnut can provide for increased stored nutritional reserves by larvae that may result in more successful over-wintering and higher fecundity in adults. This suggests that in spite of the more extensive activity of carob moth on pomegranate in Iran, populations on other host plants can have an important effect on expanding pest population sizes in following years which should be considered in control methods. PMID:20337550

  17. Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

    PubMed

    Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

    2017-10-01

    Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

  18. Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples.

    PubMed

    Calem, Maria; Bromis, Konstantinos; McGuire, Philip; Morgan, Craig; Kempton, Matthew J

    2017-01-01

    Studies of psychiatric populations have reported associations between childhood adversity and volumes of stress-related brain structures. This meta-analysis investigated these associations in non-clinical samples and therefore independent of the effects of severe mental health difficulties and their treatment. The MEDLINE database was searched for magnetic resonance imaging studies measuring brain structure in adults with and without childhood adversity. Fifteen eligible papers (1781 participants) reporting hippocampal volumes and/or amygdala volumes were pooled using a random effects meta-analysis. Those with childhood adversity had lower hippocampus volumes (hedges g = - 0.15, p  = 0.010). Controlling for gender, this difference became less evident (hedges g = - 0.12, p  = 0.124). This association differed depending on whether studies included participants with some psychopathology, though this may be due to differences in the type of adversity these studies examined. There was no strong evidence of any differences in amygdala volume. Childhood adversity may have only a modest impact on stress-related brain structures in those without significant mental health difficulties.

  19. Genome-Wide Meta-Analysis of Sciatica in Finnish Population.

    PubMed

    Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppälä, Ilkka; Juonala, Markus; Kähönen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T; Lehtimäki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti

    2016-01-01

    Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6) were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6-7%) than in other European populations (1-2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate.

  20. Genome-Wide Meta-Analysis of Sciatica in Finnish Population

    PubMed Central

    Lemmelä, Susanna; Solovieva, Svetlana; Shiri, Rahman; Benner, Christian; Heliövaara, Markku; Kettunen, Johannes; Anttila, Verneri; Ripatti, Samuli; Perola, Markus; Seppälä, Ilkka; Juonala, Markus; Kähönen, Mika; Salomaa, Veikko; Viikari, Jorma; Raitakari, Olli T.; Lehtimäki, Terho; Palotie, Aarno; Viikari-Juntura, Eira; Husgafvel-Pursiainen, Kirsti

    2016-01-01

    Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (p<1x10-6) were replicated in 776 Finnish sciatica patients and 18,489 controls. We identified five intragenic variants, with relatively low frequencies, at two novel loci associated with sciatica at genome-wide significance. These included chr9:14344410:I (rs71321981) at 9p22.3 (NFIB gene; p = 1.30x10-8, MAF = 0.08) and four variants at 15q21.2: rs145901849, rs80035109, rs190200374 and rs117458827 (MYO5A; p = 1.34x10-8, MAF = 0.06; p = 2.32x10-8, MAF = 0.07; p = 3.85x10-8, MAF = 0.06; p = 4.78x10-8, MAF = 0.07, respectively). The most significant association in the meta-analysis, a single base insertion rs71321981 within the regulatory region of the transcription factor NFIB, replicated in an independent Finnish population sample (p = 0.04). Despite identifying 15q21.2 as a promising locus, we were not able to replicate it. It was differentiated; the lead variants within 15q21.2 were more frequent in Finland (6–7%) than in other European populations (1–2%). Imputation accuracies of the three significantly associated variants (chr9:14344410:I, rs190200374, and rs80035109) were validated by genotyping. In summary, our results suggest a novel locus, 9p22.3 (NFIB), which may be involved in susceptibility to sciatica. In addition, another locus, 15q21.2, emerged as a promising one, but failed to replicate. PMID:27764105

  1. Population Analysis: Communicating in Context

    NASA Technical Reports Server (NTRS)

    Rajulu, Sudhakar; Thaxton, Sherry

    2008-01-01

    Providing accommodation to a widely varying user population presents a challenge to engineers and designers. It is often even difficult to quantify who is accommodated and who is not accommodated by designs, especially for equipment with multiple critical anthropometric dimensions. An approach to communicating levels of accommodation referred to as population analysis applies existing human factors techniques in novel ways. This paper discusses the definition of population analysis as well as major applications and case studies. The major applications of population analysis consist of providing accommodation information for multivariate problems and enhancing the value of feedback from human-in-the-loop testing. The results of these analyses range from the provision of specific accommodation percentages of the user population to recommendations of design specifications based on quantitative data. Such feedback is invaluable to designers and results in the design of products that accommodate the intended user population.

  2. MTLRP genetic polymorphism (214C>A) was associated with Type 2 diabetes in Caucasian population: a meta-analysis

    PubMed Central

    2014-01-01

    Background Previous studies reported the relation between MTLRP genetic polymorphism and type 2 diabetes, however, the conclusion were conflicting. In the present study, we performed a meta-analysis to reveal this association. Methods Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model or fixed-effect model to pool the Odds ratio (OR) according to the test of heterogeneity. Results A total of nine case–control studies included 4460 type 2 diabetes patients and 4114 healthy control subjects were analyzed. We did not found association between the MTLRP polymorphism and type 2 diabetes risk in the overall population (CC vs CA + AA: OR = 1.02; 95% CI: 0.89-1.17, P = 0.77; A vs C: OR = 1.02; 95% CI: 0.84-0.96, P = 0.62). However, in subgroup analyses stratified by ethnicity, we found significant association of MTLRP polymorphism with type 2 diabetes in Caucasians (CC vs CA + AA: OR = 1.27; 95% CI: 1.02-1.57, P = 0.03; A vs C: OR = 0.74, 95% CI: 0.60–0.91, P = 0.005). Conclusion The MTLRP polymorphism was associated with type 2 diabetes in Caucasians. PMID:25095788

  3. MTLRP genetic polymorphism (214C>A) was associated with Type 2 diabetes in Caucasian population: a meta-analysis.

    PubMed

    Chen, Li-Li; Han, Song-Mei; Tang, Fei-Fei; Li, Qiang

    2014-08-05

    Previous studies reported the relation between MTLRP genetic polymorphism and type 2 diabetes, however, the conclusion were conflicting. In the present study, we performed a meta-analysis to reveal this association. Literature retrieval, selection and assessment, data extraction, and meta-analyses were performed according to the RevMan 5.0 guidelines. In the meta-analysis, we utilized random-effect model or fixed-effect model to pool the Odds ratio (OR) according to the test of heterogeneity. A total of nine case-control studies included 4460 type 2 diabetes patients and 4114 healthy control subjects were analyzed. We did not found association between the MTLRP polymorphism and type 2 diabetes risk in the overall population (CC vs CA + AA: OR = 1.02; 95% CI: 0.89-1.17, P = 0.77; A vs C: OR = 1.02; 95% CI: 0.84-0.96, P = 0.62). However, in subgroup analyses stratified by ethnicity, we found significant association of MTLRP polymorphism with type 2 diabetes in Caucasians (CC vs CA + AA: OR = 1.27; 95% CI: 1.02-1.57, P = 0.03; A vs C: OR = 0.74, 95% CI: 0.60-0.91, P = 0.005). The MTLRP polymorphism was associated with type 2 diabetes in Caucasians.

  4. Population differentiation in allele frequencies of obesity-associated SNPs.

    PubMed

    Mao, Linyong; Fang, Yayin; Campbell, Michael; Southerland, William M

    2017-11-10

    Obesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms). We collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R 2 = 0.35, P = 0.0060) with obesity prevalence. We have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population

  5. Factors associated with quality of life in active childhood epilepsy: a population-based study.

    PubMed

    Reilly, Colin; Atkinson, Patricia; Das, Krishna B; Chin, Richard F M; Aylett, Sarah E; Burch, Victoria; Gillberg, Christopher; Scott, Rod C; Neville, Brian G R

    2015-05-01

    Improving health-related quality of life (HRQOL), rather than just reducing seizures, should be the principal goal in comprehensive management of childhood epilepsy. There is a lack of population-based data on predictors of HRQOL in childhood epilepsy. The Children with Epilepsy in Sussex Schools (CHESS) study is a prospective, population-based study involving school-aged children (5-15 years) with active epilepsy (on one or more AED and/or had a seizure in the last year) in a defined geographical area in the UK. Eighty-five of 115 (74% of eligible population) children underwent comprehensive psychological assessment including measures of cognition, behaviour, and motor functioning. Parents of the children completed the Quality of Life in Childhood Epilepsy (QOLCE).Clinical data on eligible children was extracted using a standardised pro forma. Linear regression analysis was undertaken to identify factors significantly associated with total Quality of Life in this population. Factors independently significantly associated (p < .05) with total QOLCE scores were seizures before 24 months, cognitive impairment (IQ < 85), anxiety, and parent reported school attendance difficulty. These factors were also significantly associated with total QOLCE when children with IQ < 50 were excluded from analysis. The majority of factors associated with parent reported HRQOL in active childhood epilepsy are related to neurobehavioural and/or psychosocial aspects of the condition. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  6. Association analysis of the SOX10 polymorphism with Hirschsprung disease in the Han Chinese population.

    PubMed

    Pan, Zhi-Wen; Lou, Jintu; Luo, Chunfen; Yu, Linjun; Li, Ji-Cheng

    2011-10-01

    Hirschsprung disease (HSCR, Online Mendelian Inheritance in Man 142623) is a typical developmental disorder of the enteric nervous system in which ganglion cells fail to innervate the lower gastrointestinal tract during embryonic development. SOX10 gene is involved in the normal development of the enteric nervous system. Heterozygous SOX10 mutations have been identified in patients with syndromic HSCR. However, no mutations have been reported to date to be associated to isolated HSCR patient. We thus sought to investigate whether mutations in the SOX10 are associated with isolated HSCR in the Chinese population. Polymerase chain reaction amplification and direct sequencing were used to screen 4 exons of the SOX10 gene for mutations and polymorphisms in 104 patients with sporadic HSCR and 96 ethnically matched controls in Han Chinese populations. In this study, 4 single nucleotide polymorphisms (SNPs) were identified: SNP1: c.18C>T (GAC→GAT) in exon 2; SNP2: c.122G>T (GGC→GTC) in exon 2; SNP3: IVS2+10 (C→G) in intron 2; and SNP4: c.927T>C (CAT→CAC) in exon 4. SNP1 and SNP2 were novel described polymorphisms in the Chinese population. No SOX10 mutations were found in Han Chinese with isolated HSCR. Our results revealed that there was no association between the 4 SNPs of the SOX10 gene and HSCR. This study showed that the SOX10 gene is unlikely to be a major HSCR gene in the Chinese Han population. Copyright © 2011. Published by Elsevier Inc.

  7. Population description and its role in the interpretation of genetic association

    PubMed Central

    Yu, Joon-Ho; Crouch, Julia; Fryer-Edwards, Kelly; Burke, Wylie

    2010-01-01

    Despite calls for greater clarity and precision of population description, studies have documented persistent ambiguity in the use of race/ethnicity terms in genetic research. It is unclear why investigators tolerate such ambiguity, or what effect these practices have on the evaluation of reported associations. To explore the way that population description is used to replicate and/or extend previously reported genetic observations, we examined articles describing the association of the peroxisome proliferator-activated receptor-gamma-γ Pro12Ala polymorphism with type 2 diabetes mellitus and related phenotypes, published between 1997 and 2005. The 80 articles identified were subjected to a detailed content analysis to determine (1) how sampled populations were described, (2) whether and how the choice of sample was explained, and (3) how the allele frequency and genetic association findings identified were contextualized and interpreted. In common with previous reports, we observed a variety of sample descriptions and little explanation for the choice of population investigated. Samples of European origin were typically described with greater specificity than samples of other origin. However, findings from European samples were nearly always compared to samples described as “Caucasian” and sometimes generalized to all Caucasians or to all humans. These findings suggest that care with population description, while important, may not fully address analytical concerns regarding the interpretation of variable study outcomes or ethical concerns regarding the attribution of genetic observations to broad social groups. Instead, criteria which help investigators better distinguish justified and unjustified forms of population generalization may be required. PMID:20157827

  8. Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.

    PubMed

    Guan, Yan-Ping; Yang, Xue-Xi; Yao, Guang-Yu; Qiu, Fei; Chen, Jun; Chen, Lu-Jia; Ye, Chang-Sheng; Li, Ming

    2014-01-01

    Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before

  9. Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis.

    PubMed

    Dong, Zhiyong; Zheng, Longzhi; Liu, Weimin; Wang, Cunchuan

    2018-01-01

    The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P =0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P =0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P =0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P =0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P <0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P =0.009). TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians.

  10. Association of mRNA expression of TP53 and the TP53 codon 72 Arg/Pro gene polymorphism with colorectal cancer risk in Asian population: a bioinformatics analysis and meta-analysis

    PubMed Central

    Liu, Weimin; Wang, Cunchuan

    2018-01-01

    Background The relationship between TP53 codon 72 Pro/Arg gene polymorphism and colorectal cancer risk in Asians is still controversial, and this bioinformatics analysis and meta-analysis was performed to assess the associations. Methods The association studies were identified from PubMed, and eligible reports were included. RevMan 5.3.1 software, Oncolnc, cBioPortal, and Oncomine online tools were used for statistical analysis. A random/fixed effects model was used in meta-analysis. The data were reported as risk ratios or mean differences with corresponding 95% CI. Results We confirmed that TP53 was associated with colorectal cancer, the alteration frequency of TP53 was 53% mutation and 7% deep deletion, and TP53 mRNA expression was different in different types of colorectal cancer based on The Cancer Genome Atlas database. Then, 18 studies were included that examine the association of TP53 codon 72 gene polymorphism with colorectal cancer risk in Asians. The meta-analysis indicated that TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asian population, but Arg/Arg genotype was not (Pro allele: odds ratios [OR]=1.20, 95% CI: 1.06 to 1.35, P=0.003; Pro/Pro genotype: OR=1.39, 95% CI: 1.15 to 1.69, P=0.0007; Arg/Arg genotype: OR=0.86, 95% CI: 0.74 to 1.00, P=0.05). Interestingly, in the meta-analysis of the controls from the population-based studies, we found that TP53 codon 72 Pro/Arg gene polymorphism was associated with colorectal cancer risk (Pro allele: OR=1.33, 95% CI: 1.15 to 1.55, P=0.0002; Pro/Pro genotype: OR=1.61, 95% CI: 1.28 to 2.02, P<0.0001; Arg/Arg genotype: OR=0.77, 95% CI: 0.63 to 0.93, P=0.009). Conclusion TP53 was associated with colorectal cancer, but the different value levels of mRNA expression were not associated with survival rate of colon and rectal cancer. TP53 Pro allele and Pro/Pro genotype were associated with colorectal cancer risk in Asians. PMID:29872345

  11. Genetic Structure and Relationship Analysis of an Association Population in Jute (Corchorus spp.) Evaluated by SSR Markers

    PubMed Central

    Zhang, Liwu; Yuan, Minhang; Tao, Aifen; Xu, Jiantang; Lin, Lihui; Fang, Pingping; Qi, Jianmin

    2015-01-01

    Population structure and relationship analysis is of great importance in the germplasm utilization and association mapping. Jute, comprised of white jute (C. capsularis L) and dark jute (C. olitorius L), is second to cotton in its commercial significance in the world. Here, we assessed the genetic structure and relationship in a panel of 159 jute accessions from 11 countries and regions using 63 SSRs. The structure analysis divided the 159 jute accessions from white and dark jute into Co and Cc group, further into Co1, Co2, Cc1 and Cc2 subgroups. Out of Cc1 subgroup, 81 accessions were from China and the remaining 10 accessions were from India (2), Japan (5), Thailand, Vietnam (2) and Pakistan (1). Out of Cc2 subgroup, 35 accessions were from China, and the remaining 3 accessions were from India, Pakistan and Thailand respectively. It can be inferred that the genetic background of these jute accessions was not always correlative with their geographical regions. Similar results were found in Co1 and Co2 subgroups. Analysis of molecular variance revealed 81% molecular variation between groups but it was low (19%) within subgroups, which further confirmed the genetic differentiation between the two groups. The genetic relationship analysis showed that the most diverse genotypes were Maliyeshengchangguo and Changguozhongyueyin in dark jute, BZ-2-2, Aidianyehuangma, Yangjuchiyuanguo, Zijinhuangma and Jute 179 in white jute, which could be used as the potential parents in breeding programs for jute improvement. These results would be very useful for association studies and breeding in jute. PMID:26035301

  12. Genetic Structure and Relationship Analysis of an Association Population in Jute (Corchorus spp.) Evaluated by SSR Markers.

    PubMed

    Zhang, Liwu; Yuan, Minhang; Tao, Aifen; Xu, Jiantang; Lin, Lihui; Fang, Pingping; Qi, Jianmin

    2015-01-01

    Population structure and relationship analysis is of great importance in the germplasm utilization and association mapping. Jute, comprised of white jute (C. capsularis L) and dark jute (C. olitorius L), is second to cotton in its commercial significance in the world. Here, we assessed the genetic structure and relationship in a panel of 159 jute accessions from 11 countries and regions using 63 SSRs. The structure analysis divided the 159 jute accessions from white and dark jute into Co and Cc group, further into Co1, Co2, Cc1 and Cc2 subgroups. Out of Cc1 subgroup, 81 accessions were from China and the remaining 10 accessions were from India (2), Japan (5), Thailand, Vietnam (2) and Pakistan (1). Out of Cc2 subgroup, 35 accessions were from China, and the remaining 3 accessions were from India, Pakistan and Thailand respectively. It can be inferred that the genetic background of these jute accessions was not always correlative with their geographical regions. Similar results were found in Co1 and Co2 subgroups. Analysis of molecular variance revealed 81% molecular variation between groups but it was low (19%) within subgroups, which further confirmed the genetic differentiation between the two groups. The genetic relationship analysis showed that the most diverse genotypes were Maliyeshengchangguo and Changguozhongyueyin in dark jute, BZ-2-2, Aidianyehuangma, Yangjuchiyuanguo, Zijinhuangma and Jute 179 in white jute, which could be used as the potential parents in breeding programs for jute improvement. These results would be very useful for association studies and breeding in jute.

  13. Association of GWAS Top Genes With Late-Onset Alzheimer's Disease in Colombian Population.

    PubMed

    Moreno, Diana Jennifer; Ruiz, Susana; Ríos, Ángela; Lopera, Francisco; Ostos, Henry; Via, Marc; Bedoya, Gabriel

    2017-02-01

    The association of variants in CLU, CR1, PICALM, BIN1, ABCA7, and CD33 genes with late-onset Alzheimer's disease (LOAD) was evaluated and confirmed through genome-wide association study. However, it is unknown whether these associations can be replicated in admixed populations. The association of 14 single-nucleotide polymorphisms in those genes was evaluated in 280 LOAD cases and 357 controls from the Colombian population. In a multivariate analysis using age, gender, APOE∊4 status, and admixture covariates, significant associations were obtained ( P < .05) for variants in BIN1 (rs744373, odds ratio [OR]: 1.42), CLU (rs11136000, OR: 0.66), PICALM (rs541458, OR: 0.69), ABCA7 (rs3764650, OR: 1.7), and CD33 (rs3865444, OR: 1.12). Likewise, a significant interaction effect was observed between CLU and CR1 variants with APOE. This study replicated the associations previously reported in populations of European ancestry and shows that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene-gene interactions in the etiology of neurodegenerative diseases.

  14. LINE-1 hypomethylation is associated with the risk of coronary heart disease in Chinese population.

    PubMed

    Wei, Li; Liu, Shuchuan; Su, Zhendong; Cheng, Rongchao; Bai, Xiuping; Li, Xueqi

    2014-05-01

    Global methylation level in blood leukocyte DNA has been associated with the risk of coronary heart disease (CHD), with inconsistent results in various populations. Similar data are lacking in Chinese population where different genetic, lifestyle and environmental factors may affect DNA methylation and its risk relationship with CHD. To examine whether global methylation is associated with the risk of CHD in Chinese population. A total of 334 cases with CHD and 788 healthy controls were included. Global methylation in blood leukocyte DNA was estimated by analyzing LINE-1 repeats using bisulfite pyrosequencing. In an initial analysis restricted to control subjects, LINE-1 level reduced significantly with aging, elevated total cholesterol, and diagnosis of diabetes. In the case-control analysis, reduced LINE-1 methylation was associated with increased risk of CHD; analysis by quartile revealed odds ratios (95%CI) of 0.9 (0.6-1.4), 1.9 (1.3-2.9) and 2.3 (1.6-3.5) for the third, second and first (lowest) quartile (Ptrend < 0.001), respectively, compared to the fourth (highest) quartile. Lower (associated with a 2.2-fold (95%CI = 1.7-3.0) increased risk of CHD. The lower LINE-1-related CHD risk estimates tended to be stronger among subjects with the highest tertile of homocysteine (Pinteraction = 0.042) and those with diagnosis of hypertension (Pinteraction = 0.012). LINE-1 hypomethylation is associated with the risk of CHD in Chinese population. Potential CHD risk factors such as older age, elevated total cholesterol, and diagnosis of diabetes may have impact on global DNA methylation, whereby exerting their effect on CHD risk.

  15. ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

    PubMed

    Zhang, Guohong; Mai, Ruiqin; Huang, Bo

    2010-10-27

    Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07). Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.

  16. Which population groups are most unaware of CVD risks associated with sitting time?

    PubMed

    Duncan, Mitch J; Gilson, Nicholas; Vandelanotte, Corneel

    2014-08-01

    Prolonged sitting is an emerging risk factor for poor health yet few studies have examined awareness of the risks associated with sitting behaviours. This study identifies the population subgroups with the highest levels of unawareness regarding the cardiovascular disease (CVD) risks associated with sitting behaviours. Adults (n=1256) living in Queensland, Australia completed a telephone-based survey in 2011, analysis conducted in 2013. The survey assessed participant's socio-demographic characteristics, physical activity, sitting behaviours and awareness of CVD risks associated with three sitting behaviours: 1) sitting for prolonged periods, 2), sitting for prolonged periods whilst also engaging in regular physical activity, and 3) breaking up periods of prolonged sitting with short activity breaks. Population sub-groups with the highest levels of unawareness were identified based on socio-demographic and behavioural characteristics using signal detection analysis. Unawareness ranged from 23.3% to 67.0%. Age was the most important variable in differentiating awareness levels; younger adults had higher levels of unawareness. Body mass index, physical activity, TV viewing, employment status and time spent at work also identified population sub-groups. Unawareness of CVD risk for prolonged sitting was moderately high overall. Younger adults had high levels of unawareness on all of the outcomes examined. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Discrete associations of the GCKR variant with metabolic risk in a Chinese population: longitudinal change analysis.

    PubMed

    Xu, Min; Lv, Xiaofei; Xie, Lan; Huang, Xiaolin; Huang, Ya; Chen, Ying; Peng, Kui; Wang, Po; Wang, Weiqing; Qi, Lu; Bi, Yufang; Sun, Yimin; Ning, Guang

    2016-02-01

    Glucokinase regulatory protein gene (GCKR) variant rs780092 is a novel genetic variant associated with serum triacylglycerol (TG) identified in a genome-wide association study in East Asians. We aimed to investigate associations of rs780092 with incident type 2 diabetes and dyslipidaemia, and the longitudinal changes in glucose and lipid levels. A community-based prospective cohort study was conducted at baseline in 2008, including 5,613 non-diabetic participants (37% male, mean age 57.6 years) with 5 years of follow-up. Blood glucose and lipid was measured at baseline and follow-up. Each rs780092 T-allele was associated with a 17% lower risk of incident type 2 diabetes (HR 0.83 [95% CI 0.73, 0.95]) and 36% higher risk of incident hypertriacylglycerolaemia (OR 1.36 [95% CI 1.08, 1.72]), after adjustment for baseline fasting glucose and TG and other confounders. The T-allele was associated with a 5 year increasing level of log10 TG (β ± SE, 0.01 ± 0.004, p = 0.005). Mediation analysis showed that both baseline TG and the 5 year increase in log10 TG were significant mediators in the associations of rs780092 with risk of diabetes. The risk of incident type 2 diabetes associated with 1 SD increase in total and LDL-cholesterol was 35% and 22% lower in TT carriers compared with CC carriers, respectively (both p for interaction ≤ 0.04). The GCKR rs780092 variant showed opposite-directional associations with type 2 diabetes and hypertriacylglycerolaemia in a Chinese population. Both baseline level and 5 year change in serum TG were mediators of the association between the genetic variant and type 2 diabetes.

  18. Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations

    PubMed Central

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L.; Nalls, Michael A.; Sung, Yun Ju; Tayo, Bamidele O.; Sun, Yan V.; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D.; Young, J. Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L.; Andrews, Jeanette S.; Smith, Jennifer A.; Faul, Jessica D.; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S.; Musani, Solomon K.; Srinivasan, Sathanur; Velez Edwards, Digna R.; Wang, Heming; Becker, Lewis C.; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I.; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W.; Evans, Michele K.; Guo, Xiuqing; Garcia, Melissa E.; Jensen, Rich; Keller, Margaux F.; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W.; Moore, Jason H.; Morrison, Alanna C.; Mosley, Thomas H.; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F.; Ridker, Paul M.; Salako, Babatunde; Singleton, Andrew B.; Shriner, Daniel; Taylor, Kent D.; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M.; Yanek, Lisa R.; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N.; Howard, Virginia J.; Karczewsk, Konrad J.; Lanktree, Matthew B.; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Jeon, Jae-Pil; Kim, Sung Soo; Han, Bok-Ghee; Cho, Yoon Shin; Sim, Xueling; Tay, Wan Ting; Ong, Rick Twee Hee; Seielstad, Mark; Liu, Jian Jun; Aung, Tin; Wong, Tien Yin; Teo, Yik Ying; Tai, E. Shyong; Chen, Chien-Hsiun; Chang, Li-ching; Chen, Yuan-Tsong; Wu, Jer-Yuarn; Kelly, Tanika N.; Gu, Dongfeng; Hixson, James E.; Sung, Yun Ju; He, Jiang; Tabara, Yasuharu; Kokubo, Yoshihiro; Miki, Tetsuro; Iwai, Naoharu; Kato, Norihiro; Takeuchi, Fumihiko; Katsuya, Tomohiro; Nabika, Toru; Sugiyama, Takao; Zhang, Yi; Huang, Wei; Zhang, Xuegong; Zhou, Xueya; Jin, Li; Zhu, Dingliang; Psaty, Bruce M.; Schork, Nicholas J.; Weir, David R.; Rotimi, Charles N.; Sale, Michele M.; Harris, Tamara; Kardia, Sharon L.R.; Hunt, Steven C.; Arnett, Donna; Redline, Susan; Cooper, Richard S.; Risch, Neil J.; Rao, D.C.; Rotter, Jerome I.; Chakravarti, Aravinda; Reiner, Alex P.; Levy, Daniel; Keating, Brendan J.; Zhu, Xiaofeng

    2013-01-01

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10−8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. PMID:23972371

  19. Genome-wide association analysis of gender differences in major depressive disorder in the Netherlands NESDA and NTR population-based samples.

    PubMed

    Aragam, Nagesh; Wang, Ke-Sheng; Pan, Yue

    2011-10-01

    Major depressive disorder (MDD) is a universally prevalent, genetic, and environment dependent mental condition that disables people of every culture, race, gender, and age. While the gender differences for MDD have been widely reported in literature, few genome-wide analyses of gender differences have been reported to date. We conducted a genome-wide association analysis of gender differences for MDD using the Netherlands NESDA and NTR population-based samples (1726 cases and 1630 controls). PLINK software was used to analyze the genome-wide association data of Perlegen 600 K SNP Chips. We identified 40 male-specific and 56 female-specific MDD associated SNPs with P-values less than 10(-4). The best male-specific SNP was rs9352774 (P=2.26 × 10(-6)) within LGSN gene while the best female-specific SNP was rs2715148 (P=5.64 × 10(-7)) within PCLO gene. We also found 38 SNPs showing gene × gender interactions in influencing MDD (P<10(-4)). The best SNP was rs12692709 (P=5.75 × 10(-6)) near FIGN gene at 2q24.3 while the next best SNP was rs11039588 (P=1.16 × 10(-5)) within OR4B1 gene. The findings from this study need be replicated in other populations. These results provide genetic basis for gender differences in MDD and will serve as a resource for replication in other populations to elucidate the potential role of these genetic variants in MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.

    PubMed

    Gichohi-Wainaina, Wanjiku N; Tanaka, Toshiko; Towers, G Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F; Harryvan, Jan; Boekschoten, Mark V; Feskens, Edith J; Melse-Boonstra, Alida

    2016-01-01

    Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.

  1. Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry

    PubMed Central

    Tanaka, Toshiko; Towers, G. Wayne; Verhoef, Hans; Veenemans, Jacobien; Talsma, Elise F.; Harryvan, Jan; Boekschoten, Mark V.; Feskens, Edith J.; Melse-Boonstra, Alida

    2016-01-01

    Background Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. Methods We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. Results In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (β = -0.19, P = 0.02) and rs4820268 (β = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (β = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. Conclusions In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations. PMID:27332551

  2. The association between ALS and population density: A population based study.

    PubMed

    Scott, Kirsten M; Abhinav, Kumar; Wijesekera, Lokesh; Ganesalingam, Jeban; Goldstein, Laura H; Janssen, Anna; Dougherty, Andrew; Willey, Emma; Stanton, Biba R; Turner, Martin R; Ampong, Mary-Ann; Sakel, Mohammed; Orrell, Richard; Howard, Robin; Shaw, Christopher E; Nigel Leigh, P; Al-Chalabi, Ammar

    2010-10-01

    We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis.

  3. The association between ALS and population density: A population based study

    PubMed Central

    SCOTT, KIRSTEN M.; ABHINAV, KUMAR; WIJESEKERA, LOKESH; GANESALINGAM, JEBAN; GOLDSTEIN, LAURA H.; JANSSEN, ANNA; DOUGHERTY, ANDREW; WILLEY, EMMA; STANTON, BIBA R.; TURNER, MARTIN R.; AMPONG, MARY-ANN; SAKEL, MOHAMMED; ORRELL, RICHARD; HOWARD, ROBIN; SHAW, CHRISTOPHER E.; LEIGH, P. NIGEL; AL-CHALABI, AMMAR

    2011-01-01

    We aimed to assess whether rural residence is associated with amyotrophic lateral sclerosis in the south-east of England using a population based register. Previous studies in different populations have produced contradictory findings. Residence defined by London borough or non-metropolitan district at time of diagnosis was recorded for each incident case in the South-East England ALS Register between 1995 and 2005. Each of the 26 boroughs or districts of the catchment area of the register was classified according to population density. Age- and sex-adjusted incidence of ALS was calculated for each region and the relationship with population density tested by linear regression, thereby controlling for the underlying population structure. We found that population density in region of residence at diagnosis explained 25% of the variance in ALS rates (r = 0.5, p < 0.01). Thus, in this cohort in the south-east of England, people with ALS were more likely to be resident in areas of high population density at diagnosis. PMID:20429684

  4. Chromosome 9p21 In Ischemic Stroke: Population Structure and Meta-Analysis

    PubMed Central

    Anderson, CD; Biffi, A; Rost, NS; Cortellini, L; Furie, KL; Rosand, J

    2011-01-01

    Background and Purpose Sequence variants on chromosome 9p21.3 are implicated in coronary artery disease (CAD) and myocardial infarction (MI), but studies in ischemic stroke have produced inconsistent results. We investigated whether these conflicting findings were due to false positive studies confounded by population stratification, or false negative studies that failed to account for effects specific to certain stroke subtypes. Methods After assessing for population stratification at 9p21.3 using genome-wide data, we meta-analyzed 8 ischemic stroke studies. This analysis focused on two single nucleotide polymorphisms (SNPs), rs1537378 and rs10757278, as these variants are in strong linkage disequilibrium with most SNPs analyzed in prior studies of the region. Results Principal component analysis of the genome-wide data showed no evidence of population stratification at that locus. Meta-analysis confirmed that both rs1537378 and rs10757278 are risk factors for ischemic stroke (odds ratios 1.09, [p = 0.0014], and 1.11, [p = 0.001] respectively). Subtype analysis revealed a substantial increase in the effect of each SNP for risk of large artery (LA) stroke, achieving an effect size similar to that seen in CAD/MI. Conclusions Variants on 9p21.3 are associated with ischemic stroke, and restriction of analysis to LA stroke increases effect size towards that observed in prior association studies of CAD/MI. Previous inconsistent findings are best explained by this subtype-specificity rather than any unmeasured confounding by population stratification. PMID:20395606

  5. Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals

    PubMed Central

    Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

    2015-01-01

    Objective To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Methods Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. Results A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. Conclusions The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. PMID:26416511

  6. Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis.

    PubMed

    Shaw, Souradet Y; Blanchard, James F; Bernstein, Charles N

    2015-04-01

    Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

  7. 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

  8. An association between autumn birth and clozapine treatment in patients with schizophrenia: a population-based analysis.

    PubMed

    Sørensen, Holger J; Foldager, Leslie; Røge, Rasmus; Pristed, Sofie Gry; Andreasen, Jesper T; Nielsen, Jimmi

    2014-08-01

    Numerous studies on seasonality of birth and schizophrenia risk have been published but it is uncertain whether, among those with schizophrenia, refractory illness exhibits any predilection for birth month. We hypothesized and examined whether a season of birth effect was present in patients with schizophrenia with a history of clozapine treatment. Using record linkage with Danish registers, we examined patients with schizophrenia born between 1950 and 1970, and between 1995 and 2009 and Cox regression analysis was used to examine season of birth in relation to history of clozapine treatment. In a study population corresponding to 60,062 person-years from 5328 individuals with schizophrenia of which 1223 (23%) received at least one clozapine prescription, birth in the autumn (September-November) was associated with clozapine treatment (HR = 1.24; 95% CI 1.07-1.46) when compared with birth in the spring (March-May). Although replication studies are needed, this is the first evidence from a nationwide study suggesting a possible season-associated risk of clozapine treatment in schizophrenia. The reasons for this relationship remain to be further investigated but might be partially explained by early exposures such as winter flu season and low vitamin D levels.

  9. Associations of body mass index with cancer incidence among populations, genders, and menopausal status: A systematic review and meta-analysis.

    PubMed

    Wang, Jun; Yang, Dong-Lin; Chen, Zhong-Zhu; Gou, Ben-Fu

    2016-06-01

    In order to further reveal the differences of association between body mass index (BMI) and cancer incidence across populations, genders, and menopausal status, we performed comprehensive meta-analysis with eligible citations. The risk ratio (RR) of incidence at 10 different cancer sites (per 5kg/m(2) increase in BMI) were quantified separately by employing generalized least-squares to estimate trends, and combined by meta-analyses. We observed significantly stronger association between increased BMI and breast cancer incidence in the Asia-Pacific group (RR 1.18:1.11-1.26) than in European-Australian (1.05:1.00-1.09) and North-American group (1.06:1.03-1.08) (meta-regression p<0.05). No association between increased BMI and pancreatic cancer incidence (0.94:0.71-1.24) was shown in the Asia-Pacific group (meta-regression p<0.05), whereas positive associations were found in other two groups. A significantly higher RR in men was found for colorectal cancer in comparison with women (meta-regression p<0.05). Compared with postmenopausal women, premenopausal women displayed significantly higher RR for ovarian cancer (pre- vs. post-=1.10 vs. 1.01, meta-regression p<0.05), but lower RR for breast cancer (pre- vs. post-=0.99 vs. 1.11, meta-regression p<0.0001). Our results indicate that overweight or obesity is a strong risk factor of cancer incidence at several cancer sites. Genders, populations, and menopausal status are important factors effecting the association between obesity and cancer incidence for certain cancer types. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Relation Between Inflation in Type-I and Type-II Error Rate and Population Divergence in Genome-Wide Association Analysis of Multi-Ethnic Populations.

    PubMed

    Derks, E M; Zwinderman, A H; Gamazon, E R

    2017-05-01

    Population divergence impacts the degree of population stratification in Genome Wide Association Studies. We aim to: (i) investigate type-I error rate as a function of population divergence (F ST ) in multi-ethnic (admixed) populations; (ii) evaluate the statistical power and effect size estimates; and (iii) investigate the impact of population stratification on the results of gene-based analyses. Quantitative phenotypes were simulated. Type-I error rate was investigated for Single Nucleotide Polymorphisms (SNPs) with varying levels of F ST between the ancestral European and African populations. Type-II error rate was investigated for a SNP characterized by a high value of F ST . In all tests, genomic MDS components were included to correct for population stratification. Type-I and type-II error rate was adequately controlled in a population that included two distinct ethnic populations but not in admixed samples. Statistical power was reduced in the admixed samples. Gene-based tests showed no residual inflation in type-I error rate.

  11. A comparative analysis of genetic diversity of candidate genes associated with type 2 diabetes in worldwide populations.

    PubMed

    Gong, Xian; Zhang, Chao; Yiliyasi·Aisa, Yiliyasi·Aisa; Shi, Ying; Yang, Xue-wei; NuersimanguliAosiman, NuersimanguliAosiman; Guan, Ya-qun; Xu, Shu-hua

    2016-06-20

    Over the last decade, a larger number of type 2 diabetes mellitus (T2DM) susceptible candidate genes have been reported by numerous genome-wide association studies (GWAS). Understanding the genetic diversity of these candidate genes among worldwide populations not only facilitates to elucidating the genetic mechanism of T2DM, but also provides guidance to further studies of pathogenesis of T2DM in any certain population. In this study, we identified 170 genes or genomic regions associated with T2DM by searching the GWAS databases and related literatures. We next analyzed the genetic diversity of these genes (or genomic regions) among present-day human populations by curetting the 1000 Genomes Projects phase1 dataset covering 14 worldwide populations. We further compared the characteristics of T2DM genes in different populations. No significant differences of genetic diversity were observed among the 14 worldwide populations between the T2DM candidate genes and the non-T2DM genes in terms of overall pattern. However, we observed some genes, such as IL20RA, RNMTL1-NXN, NOTCH2, ADRA2A-BTBD7P2, TBC1D4, RBM38-HMGB1P1, UBE2E2, and PPARD, show considerable differentiation between populations. In particular, IL20RA (FST=0.1521) displays the greatest population difference which is mainly contributed by that between Africans and non-Africans. Moreover, we revealed genetic differences between East Asians and Europeans on some candidate genes such as DGKB-AGMO (FST=0.173) and JAZF1 (FST=0.182). Our results indicate that some T2DM susceptible candidate genes harbor highly-differentiated variants between populations. These analyses, despite preliminary, should advance our understanding of the population difference of susceptibility to T2DM and provide insightful reference that future studies can relay on.

  12. Meta-analysis genomewide association of pork quality traits: ultimate pH and shear force

    USDA-ARS?s Scientific Manuscript database

    It is common practice to perform genome-wide association analysis (GWA) using a genomic evaluation model of a single population. Joint analysis of several populations is more difficult. An alternative to joint analysis could be the meta-analysis (MA) of several GWA from independent genomic evaluatio...

  13. Trichloroethylene Is Associated with Kidney Cancer Mortality: A Population-based Analysis.

    PubMed

    Alanee, Shaheen; Clemons, Joseph; Zahnd, Whitney; Sadowski, Daniel; Dynda, Danuta

    2015-07-01

    To examine the association between the distribution of trichloroethylene (TCE) exposure and mortality from kidney cancer (Kca) across United States counties. Multiple linear regression was used to assess the association of TCE discharges from industrial sites and age-adjusted incidence and mortality rates for Kca during 2005 through 2010, controlling for confounders. A total of 163 counties were included in analysis. We observed an excess risk of Kca mortality associated with higher amounts of environmental TCE releases. A significant dose-response relationship was observed between TCE releases and Kca mortality in females. Smoking, education, income, hypertension, and obesity were significant predictors of incidence and mortality, consistent with previous research on the epidemiology of Kca. TCE exposure may increase the risk of mortality from Kca, an association not highlighted before. There is a need for policy measures to limit TCE discharge to the environment if these results are validated. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

    PubMed

    Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L; Nalls, Michael A; Sung, Yun Ju; Tayo, Bamidele O; Sun, Yan V; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D; Young, J Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L; Andrews, Jeanette S; Smith, Jennifer A; Faul, Jessica D; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S; Musani, Solomon K; Srinivasan, Sathanur; Velez Edwards, Digna R; Wang, Heming; Becker, Lewis C; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I; Ehret, Georg; Chen, Wei-Min; Chen, Guanjie; Chen, Wei; Ding, Jingzhong; Dreisbach, Albert W; Evans, Michele K; Guo, Xiuqing; Garcia, Melissa E; Jensen, Rich; Keller, Margaux F; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W; Moore, Jason H; Morrison, Alanna C; Mosley, Thomas H; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F; Ridker, Paul M; Salako, Babatunde; Singleton, Andrew B; Shriner, Daniel; Taylor, Kent D; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M; Yanek, Lisa R; Zhao, Wei; Zonderman, Alan B; Becker, Diane M; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N; Howard, Virginia J; Karczewsk, Konrad J; Lanktree, Matthew B; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M; Schork, Nicholas J; Weir, David R; Rotimi, Charles N; Sale, Michele M; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven C; Arnett, Donna; Redline, Susan; Cooper, Richard S; Risch, Neil J; Rao, D C; Rotter, Jerome I; Chakravarti, Aravinda; Reiner, Alex P; Levy, Daniel; Keating, Brendan J; Zhu, Xiaofeng

    2013-09-05

    High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. GWAMA: software for genome-wide association meta-analysis.

    PubMed

    Mägi, Reedik; Morris, Andrew P

    2010-05-28

    Despite the recent success of genome-wide association studies in identifying novel loci contributing effects to complex human traits, such as type 2 diabetes and obesity, much of the genetic component of variation in these phenotypes remains unexplained. One way to improving power to detect further novel loci is through meta-analysis of studies from the same population, increasing the sample size over any individual study. Although statistical software analysis packages incorporate routines for meta-analysis, they are ill equipped to meet the challenges of the scale and complexity of data generated in genome-wide association studies. We have developed flexible, open-source software for the meta-analysis of genome-wide association studies. The software incorporates a variety of error trapping facilities, and provides a range of meta-analysis summary statistics. The software is distributed with scripts that allow simple formatting of files containing the results of each association study and generate graphical summaries of genome-wide meta-analysis results. The GWAMA (Genome-Wide Association Meta-Analysis) software has been developed to perform meta-analysis of summary statistics generated from genome-wide association studies of dichotomous phenotypes or quantitative traits. Software with source files, documentation and example data files are freely available online at http://www.well.ox.ac.uk/GWAMA.

  16. An epigenome-wide association analysis of cardiac autonomic responses among a population of welders.

    PubMed

    Zhang, Jinming; Liu, Zhonghua; Umukoro, Peter E; Cavallari, Jennifer M; Fang, Shona C; Weisskopf, Marc G; Lin, Xihong; Mittleman, Murray A; Christiani, David C

    2017-02-01

    DNA methylation is one of the potential epigenetic mechanisms associated with various adverse cardiovascular effects; however, its association with cardiac autonomic dysfunction, in particular, is unknown. In the current study, we aimed to identify epigenetic variants associated with alterations in cardiac autonomic responses. Cardiac autonomic responses were measured with two novel markers: acceleration capacity (AC) and deceleration capacity (DC). We examined DNA methylation levels at more than 472,506 CpG probes through the Illumina Infinium HumanMethylation450 BeadChip assay. We conducted separate linear mixed models to examine associations of DNA methylation levels at each CpG with AC and DC. One CpG (cg26829071) located in the GPR133 gene was negatively associated with DC values after multiple testing corrections through false discovery rate. Our study suggests the potential functional importance of methylation in cardiac autonomic responses. Findings from the current study need to be replicated in future studies in a larger population.

  17. Social deprivation and population density are not associated with small area risk of amyotrophic lateral sclerosis.

    PubMed

    Rooney, James P K; Tobin, Katy; Crampsie, Arlene; Vajda, Alice; Heverin, Mark; McLaughlin, Russell; Staines, Anthony; Hardiman, Orla

    2015-10-01

    Evidence of an association between areal ALS risk and population density has been previously reported. We aim to examine ALS spatial incidence in Ireland using small areas, to compare this analysis with our previous analysis of larger areas and to examine the associations between population density, social deprivation and ALS incidence. Residential area social deprivation has not been previously investigated as a risk factor for ALS. Using the Irish ALS register, we included all cases of ALS diagnosed in Ireland from 1995-2013. 2006 census data was used to calculate age and sex standardised expected cases per small area. Social deprivation was assessed using the pobalHP deprivation index. Bayesian smoothing was used to calculate small area relative risk for ALS, whilst cluster analysis was performed using SaTScan. The effects of population density and social deprivation were tested in two ways: (1) as covariates in the Bayesian spatial model; (2) via post-Bayesian regression. 1701 cases were included. Bayesian smoothed maps of relative risk at small area resolution matched closely to our previous analysis at a larger area resolution. Cluster analysis identified two areas of significant low risk. These areas did not correlate with population density or social deprivation indices. Two areas showing low frequency of ALS have been identified in the Republic of Ireland. These areas do not correlate with population density or residential area social deprivation, indicating that other reasons, such as genetic admixture may account for the observed findings. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study.

    PubMed

    Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H; Allison, Matthew A; Ix, Joachim H; Jenny, Nancy S; Wassel, Christina L

    2018-04-01

    Several biomarkers of inflammation and coagulation have been implicated in lower extremity atherosclerosis. We utilized an exploratory factor analysis (EFA) to identify distinct factors derived from circulating inflammatory and coagulation biomarkers then examined the associations of these factors with measures of lower extremity subclinical atherosclerosis, including the ankle-brachial index (ABI), common and superficial femoral intima-media thickness (IMT), and atherosclerotic plaque presence, burden, and characteristics. The San Diego Population Study (SDPS) is a prospective, community-living, multi-ethnic cohort of 1103 men and women averaged age 70. Regression analysis was used to assess cross-sectional associations between the identified groupings of biomarkers (factors) and the ABI and femoral artery atherosclerosis measurements. Two biomarker factors emerged from the factor analysis. Factor 1 consisting of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen was significantly associated with higher odds (OR = 1.99, p < 0.01) of a borderline ABI value (0.91-0.99), while Factor 2 containing D-dimer and pentraxin (PTX)-3 was significantly associated with higher common femoral artery (CFA) IMT (β = 0.23, p < 0.01) and lower ABI (β = -0.03, p < 0.01). Two groupings of biomarkers were identified via EFA of seven circulating biomarkers of inflammation and coagulation. These distinct groups are differentially associated with markers of lower extremity subclinical atherosclerosis. Our findings suggest that high inflammatory and coagulation burden were better markers of more severe lower-extremity disease as indicated by low ABI rather than early atherosclerotic lesion development in the femoral artery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Increased population density of neurosurgeons associated with decreased risk of death from motor vehicle accidents in the United States.

    PubMed

    Desai, Atman; Bekelis, Kimon; Zhao, Wenyan; Ball, Perry A

    2012-09-01

    Motor vehicle accidents (MVAs) are a leading cause of death and disability in young people. Given that a major cause of death from MVAs is traumatic brain injury, and neurosurgeons hold special expertise in this area relative to other members of a trauma team, the authors hypothesized that neurosurgeon population density would be related to reduced mortality from MVAs across US counties. The Area Resource File (2009-2010), a national health resource information database, was retrospectively analyzed. The primary outcome variable was the 3-year (2004-2006) average in MVA deaths per million population for each county. The primary independent variable was the density of neurosurgeons per million population in the year 2006. Multiple regression analysis was performed, adjusting for population density of general practitioners, urbanicity of the county, and socioeconomic status of the county. The median number of annual MVA deaths per million population, in the 3141 counties analyzed, was 226 (interquartile range [IQR] 151-323). The median number of neurosurgeons per million population was 0 (IQR 0-0), while the median number of general practitioners per million population was 274 (IQR 175-410). Using an unadjusted analysis, each increase of 1 neurosurgeon per million population was associated with 1.90 fewer MVA deaths per million population (p < 0.001). On multivariate adjusted analysis, each increase of 1 neurosurgeon per million population was associated with 1.01 fewer MVA deaths per million population (p < 0.001), with a respective decrease in MVA deaths of 0.03 per million population for an increase in 1 general practitioner (p = 0.007). Rural location, persistent poverty, and low educational level were all associated with significant increases in the rate of MVA deaths. A higher population density of neurosurgeons is associated with a significant reduction in deaths from MVAs, a major cause of death nationally. This suggests that the availability of local

  20. Plasticity in host utilization by two host-associated populations of Aphis gossypii Glover.

    PubMed

    Barman, A K; Gadhave, K R; Dutta, B; Srinivasan, R

    2018-06-01

    Biological and morphological plasticity in polyphagous insect herbivores allow them to exploit diverse host plant species. Geographical differences in resource availability can lead to preferential host exploitation and result in inconsistent host specialization. Biological and molecular data provide insights into specialization and plasticity of such herbivore populations. In agricultural landscapes, Aphis gossypii encounters several crop and non-crop hosts, which exist in temporal and spatial proximity. We investigated the host-specialization of two A. gossypii host-associated populations (HAPs), which were field collected from cotton and squash (cotton-associated population and melon-associated population), and later maintained separately in the greenhouse. The two aphid populations were exposed to seven plant species (cotton, okra, watermelon, squash, cucumber, pigweed, and morning glory), and evaluated for their host utilization plasticity by estimating aphid's fitness parameters (nymphal period, adult period, fecundity, and intrinsic rate of increase). Four phenotypical characters (body length, head capsule width, hind tibia length and cornicle length) were also measured from the resulting 14 different HAP × host plant combinations. Phylogenetic analysis of mitochondrial COI sequences showed no genetic variation between the two HAPs. Fitness parameters indicated a significant variation between the two aphid populations, and the variation was influenced by host plants. The performance of melon-aphids was poor (up to 89% reduction in fecundity) on malvaceous hosts, cotton and okra. However, cotton-aphids performed better on cucurbitaceous hosts, squash and watermelon (up to 66% increased fecundity) compared with the natal host, cotton. Both HAPs were able to reproduce on two weed hosts. Cotton-aphids were smaller than melon-aphids irrespective of their host plants. Results from this study suggest that the two HAPs in the study area do not have strict host

  1. Association between Thrombophilic Genes Polymorphisms and Recurrent Pregnancy Loss Susceptibility in the Iranian Population: a Systematic Review and Meta-Analysis

    PubMed Central

    Kamali, Mahdieh; Hantoushzadeh, Sedigheh; Borna, Sedigheh; Neamatzadeh, Hossein; Mazaheri, Mahta; Noori-Shadkam, Mahmood; Haghighi, Fatemeh

    2018-01-01

    Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss (RPL) in the Iranian population. We aimed to evaluate the precise association between thrombophilic genes polymorphisms (MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G) and RPL risk in the Iranian population. PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. In total, 37 case-control studies in 18 relevant publications were selected: 1,199, 1,194, 630, 830, and 955 RPL cases and 1,079, 1079, 594, 794, and 499 controls for MTHFR C677T, MTHFR A1298C,Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G, respectively. The results indicated a significant increased risk of RPL in all genetic models in the population. Also, Prothrombin G20210A and FVL G1691A as well as PAI-1 4G/5G polymorphisms were associated with RPL risk in the Iranian population. Hence, thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population. PMID:28734273

  2. Control for Population Structure and Relatedness for Binary Traits in Genetic Association Studies via Logistic Mixed Models

    PubMed Central

    Chen, Han; Wang, Chaolong; Conomos, Matthew P.; Stilp, Adrienne M.; Li, Zilin; Sofer, Tamar; Szpiro, Adam A.; Chen, Wei; Brehm, John M.; Celedón, Juan C.; Redline, Susan; Papanicolaou, George J.; Thornton, Timothy A.; Laurie, Cathy C.; Rice, Kenneth; Lin, Xihong

    2016-01-01

    Linear mixed models (LMMs) are widely used in genome-wide association studies (GWASs) to account for population structure and relatedness, for both continuous and binary traits. Motivated by the failure of LMMs to control type I errors in a GWAS of asthma, a binary trait, we show that LMMs are generally inappropriate for analyzing binary traits when population stratification leads to violation of the LMM’s constant-residual variance assumption. To overcome this problem, we develop a computationally efficient logistic mixed model approach for genome-wide analysis of binary traits, the generalized linear mixed model association test (GMMAT). This approach fits a logistic mixed model once per GWAS and performs score tests under the null hypothesis of no association between a binary trait and individual genetic variants. We show in simulation studies and real data analysis that GMMAT effectively controls for population structure and relatedness when analyzing binary traits in a wide variety of study designs. PMID:27018471

  3. Molecular analysis and conventional cytology: association between HPV and bacterial vaginosis in the cervical abnormalities of a Brazilian population.

    PubMed

    Peres, A L; Camarotti, J R S L; Cartaxo, M; Alencar, N; Stocco, R C; Beçak, W; Pontes-Filho, N T; Araújo, R F F; Lima-Filho, J L; Martins, D B G

    2015-08-14

    We investigated the association between bacterial vaginosis (BV) and human papillomavirus (HPV) infection in Papanicolaou smears in a Brazilian population. Cross-sectional analysis was performed on 673 samples collected from women attending public health centers in Olinda (PE, Brazil) by conventional cytology methodology and molecular analysis, PCR tests (GP5+/6+ and MY09/11). Cytological abnormalities, BV, and HPV-DNA were detected in 23 (3.4%) samples, 189 samples (28.1%), and 210 samples (31.2%), respectively. GP5+/6+ primers resulted in higher detection performance than MY09/11 primers, with 81% concordance between both primers (P < 0.0001). The occurrence of HPV-DNA and BV had ORs of 8.59 (P < 0.0001) and 2.91 (P = 0.0089) for abnormal cytology, respectively, whereas the concomitant presence of both infections showed an OR equal to 3.82 (P = 0.0054). Therefore, we observed an association between abnormal cervical cytology and HPV infection, BV, or both HPV infection and BV. These results highlight the necessity of monitoring patients presenting not only HPV, but also BV, as risk factors for cervical lesion development.

  4. Genetic Association Analysis of Common Variants in FOXO3 Related to Longevity in a Chinese Population

    PubMed Central

    Yan, Dongjing; Liao, Xiaoping; Wang, Xianshou; Fu, Yunxin; Cai, Wangwei

    2016-01-01

    Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007–0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20–4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies. PMID:27936216

  5. Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis.

    PubMed

    Wu, Wilfred; Clark, Erin A S; Stoddard, Gregory J; Watkins, W Scott; Esplin, M Sean; Manuck, Tracy A; Xing, Jinchuan; Varner, Michael W; Jorde, Lynn B

    2013-04-25

    Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB. We reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies.For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 - 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity. IL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is

  6. Prevalence of Diabetes and Associated Factors in the Uyghur and Han Population in Xinjiang, China.

    PubMed

    Gong, Haiying; Pa, Lize; Wang, Ke; Mu, Hebuli; Dong, Fen; Ya, Shengjiang; Xu, Guodong; Tao, Ning; Pan, Li; Wang, Bin; Shan, Guangliang

    2015-10-14

    To estimate the prevalence of diabetes and identify risk factors in the Uyghur and Han population in Xinjiang, China. A cross-sectional study in urban and rural areas in Xinjiang, including 2863 members of the Uyghur population and 3060 of the Han population aged 20 to 80 years, was conducted from June 2013 to August 2013. Data on fasting plasma glucose (FPG) and personal history of diabetes were used to estimate the prevalence of diabetes. Data on demographic characteristics, lifestyle risk factors, and lipid profiles were collected to identify risks factors using the multivariate logistic regression model. In urban areas, the age- and gender-standardized prevalence of diabetes was 8.21%, and the age- and gender-standardized prevalence of diabetes was higher in the Uyghur population (10.47%) than in the Han population (7.36%). In rural areas, the age- and gender-standardized prevalence of diabetes was 6.08%, and it did not differ significantly between the Uyghur population (5.71%) and the Han population (6.59%). The results of the multivariate logistic regression analysis showed that older age, obesity, high triglycerides (TG), and hypertension were all associated with an increased risk of diabetes in the Uyghur and Han population. Urban residence and low high-density lipoprotein cholesterol (HDL-C) were associated with an increased risk of diabetes in the Uyghur population. Being an ex-drinker was associated with an increased risk of diabetes and heavy physical activity was associated with a decreased risk of diabetes in the Han population. Our study indicates that diabetes is more prevalent in the Uyghur population compared with the Han population in urban areas. Strategies aimed at the prevention of diabetes require ethnic targeting.

  7. Serum γ-glutamyltransferase and associated damage among a She Chinese population.

    PubMed

    Lin, Y; Xu, Y; Chen, G; Huang, B; Yao, J; Chen, Z; Yao, L; Lin, F; Qiao, Y; Chen, Z; Zhu, S; Huang, H; Wen, J

    2011-08-01

    It has been suggested that serum γ-glutamyltransferase is independently associated with cardiovascular mortality and atherosclerosis. The present study is to investigate the relationship between serum γ-glutamyltransferase and potential associated damage in an adult She Chinese population. A multistage, stratified, cluster, random sampling method was used to select an ethnically representative group of individuals aged 20-80 years in the general population. Brachial-ankle pulse-wave velocity was used to assess arterial stiffness in the general population and the Toronto Clinical Neuropathy Scoring System was used to detect diabetic peripheral polyneuropathy among populations with diabetes. A total of 5385 subjects were entered into the analysis. Serum γ-glutamyltransferase levels were classified into four groups using the 25th, 50th and 75th percentiles as cut points (males: < 20, 20-29, 29-52 and > 52 U/l; females: < 13, 13-18, 18-25 and > 25 U/l). As compared with the first quartile, the relative risks of arterial stiffness were 1.418, 1.667 and 2.394 in the other three categories, respectively (test for trend P < 0.05). After adjustment in five models, serum γ-glutamyltransferase was still a risk factor of arterial stiffness. We found inverted U-shape curves in both genders and the third quartile (male: 29 52 U/l; female: 18-25 U/l) had the highest odds ratios of 1.640 and 1.529, respectively. We demonstrated that high serum γ-glutamyltransferase concentrations were directly associated with the increased risk of arterial stiffness, in general, and with peripheral polyneuropathy in subjects with diabetes in an ethnic She Chinese population. Alcohol use, gender, BMI and blood pressure were related to serum γ-glutamyltransferase and were involved in the relationship between serum γ-glutamyltransferase and brachial-ankle pulse-wave velocity. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  8. The genetic structure of fermentative vineyard-associated Saccharomyces cerevisiae populations revealed by microsatellite analysis.

    PubMed

    Schuller, Dorit; Casal, Margarida

    2007-02-01

    From the analysis of six polymorphic microsatellite loci performed in 361 Saccharomyces cerevisiae isolates, 93 alleles were identified, 52 of them being described for the first time. All these isolates have a distinct mtDNA RFLP pattern. They are derived from a pool of 1620 isolates obtained from spontaneous fermentations of grapes collected in three vineyards of the Vinho Verde Region in Portugal, during the 2001-2003 harvest seasons. For all loci analyzed, observed heterozygosity was 3-4 times lower than the expected value supposing a Hardy-Weinberg equilibrium (random mating and no evolutionary mechanisms acting), indicating a clonal structure and strong populational substructuring. Genetic differences among S. cerevisiae populations were apparent mainly from gradations in allele frequencies rather than from distinctive "diagnostic" genotypes, and the accumulation of small allele-frequency differences across six loci allowed the identification of population structures. Genetic differentiation in the same vineyard in consecutive years was of the same order of magnitude as the differences verified among the different vineyards. Correlation of genetic differentiation with the distance between sampling points within a vineyard suggested a pattern of isolation-by-distance, where genetic divergence in a vineyard increased with size. The continuous use of commercial yeasts has a limited influence on the autochthonous fermentative yeast population collected from grapes and may just slightly change populational structures of strains isolated from sites very close to the winery where they have been used. The present work is the first large-scale approach using microsatellite typing allowing a very fine resolution of indigenous S. cerevisiae populations isolated from vineyards.

  9. Associations of pregnancy-associated plasma protein-A level with essential hypertension and hypertensive disorders in pregnancy in Chinese population: a meta-analysis of 20 research studies involving 3332 individuals.

    PubMed

    Cai, Gaojun; Zhang, Bifeng; Weng, Weijin; Yang, Liping; Shi, Ganwei; Xue, Sheliang; Fu, Xingli

    2015-09-28

    To explore the associations between serum pregnancy-associated plasma protein-A (PAPP-A) level, and essential hypertension (EH) and hypertensive disorders in pregnancy (HDP) in Chinese population. Pertinent studies were independently searched in PubMed, Embase, Cochrane Library, Chinese Biomedical Database (CBM), Wanfang databases and China National Knowledge Infrastructure (CNKI). The standardised mean difference (SMD) with 95% CIs was used to estimate the size of the effect. The subgroup analyses and meta-regression analysis were performed to identify the sources of heterogeneity among studies. Sensitivity analysis was conducted to assess the stability of the results. The publication bias between studies was examined by using Begg's funnel plots and Egger's test. A total of 20 studies involving 1493 patients and 1839 controls were included in the current meta-analysis. The PAPP-A level was significantly higher in EH patients than in controls (SMD=1.960, 95% CI 1.305 to 2.615, p<0.001), and significant associations were observed in all subgroups. The PAPP-A level was also significantly higher in HDP patients than in healthy pregnant women (SMD=2.249; 95% CI 1.324 to 3.173, p<0.001). The positive association between PAPP-A level and the risk of HDP was consistently observed in all subgroups except the subgroup with low NOS score. The present meta-analysis suggests that an elevated PAPP-A level may be associated with susceptibilities to EH and HDP. 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.

  10. CHI3L1 polymorphisms associate with asthma in a Taiwanese population

    PubMed Central

    2014-01-01

    Background A genome-wide association study uncovered Chitinase 3 like 1 (CHI3L1) as a candidate gene for asthma susceptibility. CHI3L1, which encodes the YKL-40 protein, is associated with asthma in Western European and American populations and with atopy in a Korean population. However, asthma-associated polymorphisms remain unknown for a Taiwanese population. Methods We enrolled 628 adult asthmatic patients and 1:1 age-sex matched community-based controls in southern Taiwan and performed a combined effect sizes analysis to test if CHI3L1 polymorphisms were related to genetic risks for asthma in the Asian population. Ten tagSNP polymorphisms for the CHI3L1 gene were selected from the HapMap database and genotyped using a TaqMan allelic discrimination assay. Results Adjusted odds ratios of the CHI3L1 rs1538372 CC genotype (aOR = 1.97, 95% CI: 1.23–3.14) and the rs10399931 GG genotype (aOR = 1.77, 95% CI: 1.13–2.77) were significantly associated with asthma in the Taiwanese populations. Predictive values of forced expiratory volume in the first second of the forced vital capacity (12.37%, P = 0.03) and of forced vital capacity (12.10%, P = 0.036) decreased in conjunction with an increase in YKL-40 levels among CHI3L1 rs1538372 CC carriers; these values were 16.1% (P = 0.004) and 14.5% (P = 0.011), respectively, among CHI3L1 rs10399931 GG carriers. Furthermore, steroid use by asthma patients did not affect serum YKL-40 levels, but both polymorphisms had significant effects on YKL-40 levels in asthma patients who used steroids. Conclusions Our findings suggest that the CHI3L1 polymorphisms rs1538372 and rs10399931 can be used as genetic markers for predicting asthma risk in the Taiwanese population. PMID:25056157

  11. Identification of a novel locus associated with skin colour in African-admixed populations

    PubMed Central

    Hernandez-Pacheco, Natalia; Flores, Carlos; Alonso, Santos; Eng, Celeste; Mak, Angel C. Y.; Hunstman, Scott; Hu, Donglei; White, Marquitta J.; Oh, Sam S.; Meade, Kelley; Farber, Harold J.; Avila, Pedro C.; Serebrisky, Denise; Thyne, Shannon M.; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Sen, Saunak; Kumar, Rajesh; Lenoir, Michael; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Pino-Yanes, Maria

    2017-01-01

    Skin pigmentation is a complex trait that varies largely among populations. Most genome-wide association studies of this trait have been performed in Europeans and Asians. We aimed to uncover genes influencing skin colour in African-admixed individuals. We performed a genome-wide association study of melanin levels in 285 Hispanic/Latino individuals from Puerto Rico, analyzing 14 million genetic variants. A total of 82 variants with p-value ≤1 × 10−5 were followed up in 373 African Americans. Fourteen single nucleotide polymorphisms were replicated, of which nine were associated with skin colour at genome-wide significance in a meta-analysis across the two studies. These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 × 10−14, rs1426654) and SLC45A2 (minimum p = 9.71 × 10−10, rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 × 10−9, rs6602666). The most significant variant within this region is common among African-descent populations but not among Europeans or Native Americans. Our findings support the advantages of analyzing African-admixed populations to discover new genes influencing skin pigmentation. PMID:28300201

  12. Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: a case-control and meta-analysis study.

    PubMed

    Phani, Nagaraja M; Guddattu, Vasudeva; Bellampalli, Ravishankara; Seenappa, Venu; Adhikari, Prabha; Nagri, Shivashankara K; D Souza, Sydney C; Mundyat, Gopinath P; Satyamoorthy, Kapaettu; Rai, Padmalatha S

    2014-01-01

    Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran's Q, I2 statistics were used to study heterogeneity between the eligible studies. KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83-1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.

  13. Mapping of disease-associated variants in admixed populations

    PubMed Central

    2011-01-01

    Recent developments in high-throughput genotyping and whole-genome sequencing will enhance the identification of disease loci in admixed populations. We discuss how a more refined estimation of ancestry benefits both admixture mapping and association mapping, making disease loci identification in admixed populations more powerful. High-throughput genotyping and sequencing will enable refined estimation of ancestry, thus enhancing disease loci identification in admixed populations PMID:21635713

  14. Microbial Genomics of a Host-Associated Commensal Bacterium in Fragmented Populations of Endangered Takahe.

    PubMed

    Grange, Zoë L; Gartrell, Brett D; Biggs, Patrick J; Nelson, Nicola J; Anderson, Marti; French, Nigel P

    2016-05-01

    Isolation of wildlife into fragmented populations as a consequence of anthropogenic-mediated environmental change may alter host-pathogen relationships. Our understanding of some of the epidemiological features of infectious disease in vulnerable populations can be enhanced by the use of commensal bacteria as a proxy for invasive pathogens in natural ecosystems. The distinctive population structure of a well-described meta-population of a New Zealand endangered flightless bird, the takahe (Porphyrio hochstetteri), provided a unique opportunity to investigate the influence of host isolation on enteric microbial diversity. The genomic epidemiology of a prevalent rail-associated endemic commensal bacterium was explored using core genome and ribosomal multilocus sequence typing (rMLST) of 70 Campylobacter sp. nova 1 isolated from one third of the takahe population resident in multiple locations. While there was evidence of recombination between lineages, bacterial divergence appears to have occurred and multivariate analysis of 52 rMLST genes revealed location-associated differentiation of C. sp. nova 1 sequence types. Our results indicate that fragmentation and anthropogenic manipulation of populations can influence host-microbial relationships, with potential implications for niche adaptation and the evolution of micro-organisms in remote environments. This study provides a novel framework in which to explore the complex genomic epidemiology of micro-organisms in wildlife populations.

  15. Lack of association between TPH2 gene polymorphisms with major depressive disorder in multiethnic Malaysian population.

    PubMed

    Nazree, Nur Elia; Loke, Ai Chin; Zainal, Nor Zuraida; Mohamed, Zahurin

    2015-03-01

    Numerous association studies of candidate genes studies with major depressive disorder (MDD) have been conducted for many years; however, the evidence of association between genes and the risk of developing MDD still remains inconclusive. In this study, we aimed to investigate the association between the tryptophan hydroxylase 2 (TPH2) gene and MDD in three ethnic groups (Malay, Chinese and Indian) within the Malaysian population. Two hundred and sixty five MDD patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for MDD and 332 healthy controls were recruited for the study. All cases and controls were then genotyped for TPH2 polymorphisms rs1386494, rs1386495 and rs7305115. Single locus analysis in pooled and ethnically stratified subjects revealed no association between each of the three variants of the TPH2 gene with susceptibility to MDD. Strong linkage disequilibrium was detected between rs1386495 and rs1386494 in pooled subjects; however, no significant association was found in the haplotype analysis. In this study, we suggest that in both the Chinese and Indian populations, gender distribution differ significantly between cases and controls, showing that women are more at risk of developing MDD compared with men. Therefore, we suggest that the occurrence of MDD in both Chinese and Indians in the Malaysian population may be influenced by gender. Copyright © 2013 Wiley Publishing Asia Pty Ltd.

  16. Comparison of refractive errors and factors associated with spectacle use in a rural and urban South Indian population

    PubMed Central

    Prema, Raju; Sathyamangalam Ve, Ramesh; Hemamalini, Arvind; Baskaran, Mani; Kumaramanickavel, Govindaswamy; Catherine, McCarty; Vijaya, Lingam

    2008-01-01

    Purpose: To compare the prevalence of refractive errors and factors associated with spectacle use in a rural and urban south Indian population. Materials and Methods: Four thousand eight hundred subjects (age >39 years) each from rural and urban Tamil Nadu were enumerated for a population-based study. All participants underwent a complete ophthalmic evaluation including best-corrected visual acuity (BCVA), objective and subjective refraction. Out of 3924 rural responders 63.91% and out of 3850 urban responders 81.64% were phakic in the right eye with BCVA of 20/40 or better and were included in the study. Association of spectacle use and refractive errors with different parameters were analysed using logistic regression. Statistical Analysis: Chi square, t test, Chi square for trend and Pearson′s correlation coefficient were used for analysis. Results: Spectacle use was significantly higher and positively associated with literacy and employment in the urban population. The age and gender-adjusted prevalence of emmetropia, myopia of spherical equivalent (SE) ≤-0.50 diopter sphere (DS), high myopia (SE ≤-5.00DS), hyperopia (SE >0.50DS) and astigmatism ≤ 0.50 diopter cylinder (DC) were 46.8%, 31.0%, 4.3%, 17.9% and 60.4% respectively in the rural population and 29.0%, 17.6%, 1.5%, 51.9%, 59.1% respectively in the urban population. The prevalence of emmetropia decreased with age (p < 0.001); prevalence of myopia and high myopia increased with age (p = 0.001) and were associated with nuclear sclerosis (p = 0.001) in both populations. Hyperopia was commoner among women than men (p = 0.001); was positively associated with diabetes mellitus (p = 0.008) in the rural population and negatively with nuclear sclerosis (p = 0.001) in both populations. Conclusion: Spectacle use was found to be significantly lower in the rural population. The pattern of refractive errors was significantly different between both populations. PMID:18292625

  17. Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs.

    PubMed

    Tönjes, Anke; Koriath, Moritz; Schleinitz, Dorit; Dietrich, Kerstin; Böttcher, Yvonne; Rayner, Nigel W; Almgren, Peter; Enigk, Beate; Richter, Olaf; Rohm, Silvio; Fischer-Rosinsky, Antje; Pfeiffer, Andreas; Hoffmann, Katrin; Krohn, Knut; Aust, Gabriela; Spranger, Joachim; Groop, Leif; Blüher, Matthias; Kovacs, Peter; Stumvoll, Michael

    2009-12-01

    Recently, associations of several common genetic variants with height have been reported in different populations. We attempted to identify further variants associated with adult height in a self-contained population (the Sorbs in Eastern Germany) as discovery set. We performed a genome wide association study (GWAS) (approximately 390,000 genetic polymorphisms, Affymetrix gene arrays) on adult height in 929 Sorbian individuals. Subsequently, the best SNPs (P < 0.001) were taken forward to a meta-analysis together with two independent cohorts [Diabetes Genetics Initiative, British 1958 Birth Cohort, (58BC, publicly available)]. Furthermore, we genotyped our best signal for replication in two additional German cohorts (Leipzig, n = 1044 and Berlin, n = 1728). In the primary Sorbian GWAS, we identified 5 loci with a P-value < 10(-5) and 455 SNPs with P-value < 0.001. In the meta-analysis on those 455 SNPs, only two variants in GPR133 (rs1569019 and rs1976930; in LD with each other) retained a P-value at or below 10(-6) and were associated with height in the three cohorts individually. Upon replication, the SNP rs1569019 showed significant effects on height in the Leipzig cohort (P = 0.004, beta = 1.166) and in 577 men of the Berlin cohort (P = 0.049, beta = 1.127) though not in women. The combined analysis of all five cohorts (n = 6,687) resulted in a P-value of 4.7 x 10(-8) (beta = 0.949). In conclusion, our GWAS suggests novel loci influencing height. In view of the robust replication in five different cohorts, we propose GPR133 to be a novel gene associated with adult height.

  18. Association of FTO rs9939609 SNP with Obesity and Obesity- Associated Phenotypes in a North Indian Population

    PubMed Central

    Prakash, Jai; Mittal, Balraj; Srivastava, Apurva; Awasthi, Shally; Srivastava, Neena

    2016-01-01

    Objectives Obesity is a common disorder that has a significant impact on morbidity and mortality. Twin and adoption studies support the genetic influence on variation of obesity, and the estimates of the heritability of body mass index (BMI) is significantly high (30 to 70%). Variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and obesity-related phenotypes in different populations. The aim of this study was to examine the association of FTO rs9939609 with obesity and related phenotypes in North Indian subjects.   Methods Gene variants were investigated for association with obesity in 309 obese and 333 non-obese patients. Genotyping of the FTO rs9939609 single nucleotide polymorphism (SNP) was analyzed using Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments. We also measured participants fasting glucose and insulin levels, lipid profile, percentage body fat, fat mass and fat free mass.   Results Waist to hip ratio, systolic blood pressure, diastolic blood pressure, percentage body fat, fat mass, insulin concentration, and homeostasis model assessment index (HOMA-Index) showed a significant difference between the study groups. Significant associations were found for FTO rs9939609 SNP with obesity and obesity-related phenotypes. The significant associations were observed between the rs9939609 SNP and blood pressure, fat mass, insulin, and HOMA-index under a different model.   Conclusion This study presents significant association between FTO rs9939609 and obesity defined by BMI and also established the strong association with several measures of obesity in North Indian population. PMID:27168919

  19. Association of RTEL1 gene polymorphisms with stroke risk in a Chinese Han population.

    PubMed

    Cai, Yi; Zeng, Chaosheng; Su, Qingjie; Zhou, Jingxia; Li, Pengxiang; Dai, Mingming; Wang, Desheng; Long, Faqing

    2017-12-29

    We investigated the associations between single nucleotide polymorphisms (SNPs) in the regulator of telomere elongation helicase 1 ( RTEL1 ) gene and stroke in the Chinese population. A total of 400 stroke patients and 395 healthy participants were included in this study. Five SNPs in RTEL1 were genotyped and the association with stroke risk was analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to identify SNPs that correlated with stroke. Rs2297441 was associated with an increased risk of stroke in an allele model (odds ratio [OR] = 1.24, 95% confidence interval [95% CI] = 1.01-1.52, p = 0.043). Rs6089953 was associated with an increased risk of stroke under the genotype model ([OR] = 1.862, [CI] = 1.123-3.085, p = 0.016). Rs2297441 was associated with an increased risk of stroke in an additive model (OR = 1.234, 95% CI = 1.005, p = 0.045, Rs6089953, Rs6010620 and Rs6010621 were associated with an increased risk of stroke in the recessive model (Rs6089953:OR = 1.825, 95% CI = 1.121-2.969, p =0.01546; Rs6010620: OR = 1.64, 95% CI = 1.008-2.669, p =0.04656;Rs6010621:OR = 1.661, 95% CI = 1.014-2.722, p =0.04389). Our findings reveal a possible association between SNPs in the RTEL1 gene and stroke risk in Chinese population.

  20. Joint genome-wide association study for milk fatty acid traits in Chinese and Danish Holstein populations.

    PubMed

    Li, X; Buitenhuis, A J; Lund, M S; Li, C; Sun, D; Zhang, Q; Poulsen, N A; Su, G

    2015-11-01

    The identification of causal genes or genomic regions associated with fatty acids (FA) will enhance our understanding of the pathways underlying FA synthesis and provide opportunities for changing milk fat composition through a genetic approach. The linkage disequilibrium between adjacent markers is highly consistent between the Chinese and Danish Holstein populations, such that a joint genome-wide association study (GWAS) can be performed. In this study, a joint GWAS was performed for 16 milk FA traits based on data of 784 Chinese and 371 Danish Holstein cows genotyped by a high-density bovine single nucleotide polymorphism (SNP) array. A total of 486,464 SNP markers on 29 bovine autosomes were used. Bonferroni corrections were applied to adjust the significance thresholds for multiple testing at the genome- and chromosome-wide levels. According to the analysis of either the Chinese or Danish data individually, the total numbers of overlapping SNP that were significant at the chromosome level were 94 for C14:1, 208 for the C14 index, and 1 for C18:0. Joint analysis using the combined data of the 2 populations detected greater numbers of significant SNP compared with either of the individual populations alone for 7 and 10 traits at the genome- and chromosome-wide significance levels, respectively. Greater numbers of significant SNP were detected for C18:0 and the C18 index in the Chinese population compared with the joint analysis. Sixty-five significant SNP across all traits had significantly different effects in the 2 populations. Ten FA were influenced by a quantitative trait loci (QTL) region including DGAT1. Both C14:1 and the C14 index were influenced by a QTL region including SCD1 in the combined population. Other QTL regions also showed significant associations with the studied FA. A large region (14.9-24.9 Mbp) in BTA26 significantly influenced C14:1 and the C14 index in both populations, mostly likely due to the SNP in SCD1. A QTL region (69.97-73.69 Mbp

  1. Control for Population Structure and Relatedness for Binary Traits in Genetic Association Studies via Logistic Mixed Models.

    PubMed

    Chen, Han; Wang, Chaolong; Conomos, Matthew P; Stilp, Adrienne M; Li, Zilin; Sofer, Tamar; Szpiro, Adam A; Chen, Wei; Brehm, John M; Celedón, Juan C; Redline, Susan; Papanicolaou, George J; Thornton, Timothy A; Laurie, Cathy C; Rice, Kenneth; Lin, Xihong

    2016-04-07

    Linear mixed models (LMMs) are widely used in genome-wide association studies (GWASs) to account for population structure and relatedness, for both continuous and binary traits. Motivated by the failure of LMMs to control type I errors in a GWAS of asthma, a binary trait, we show that LMMs are generally inappropriate for analyzing binary traits when population stratification leads to violation of the LMM's constant-residual variance assumption. To overcome this problem, we develop a computationally efficient logistic mixed model approach for genome-wide analysis of binary traits, the generalized linear mixed model association test (GMMAT). This approach fits a logistic mixed model once per GWAS and performs score tests under the null hypothesis of no association between a binary trait and individual genetic variants. We show in simulation studies and real data analysis that GMMAT effectively controls for population structure and relatedness when analyzing binary traits in a wide variety of study designs. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  2. Genome-Wide Association Analysis of Sasang Constitution in the Korean Population

    PubMed Central

    Kim, Bu-Yeo; Jin, Hee-Jeong

    2012-01-01

    Abstract Objectives Sasang constitutional medicine is a traditional Korean medicine in which an individual is classified into one of four types of constitution: Taeum (TE), Soeum (SE) Soyang (SY), and Taeyang (TY). These constitution types are determined with biologic and physiologic characteristics, so it has been assumed that genetic factors are associated with each constitution type. Identifying the genetic elements underlying each constitution is necessary for the elucidation of the molecular mechanism of Sasang constitutional medicine. Design A total of 341,998 genetic loci across the whole genome were genotyped for 1222 subjects of defined constitution type. The genetic loci associated with each constitution type were identified and the functional connectivity of genes within these loci was analyzed using statistical text mining. Results From the difference in allele frequencies between constitution types, significant genetic loci associated with each type were identified. Chromosomes 3q27.3 (rs10937331, p=2.71×10−6), 15q22.2 (rs7180547, p=1.58×10−6), and 14q22.3 (rs12431592, p=1.31×10−6) were most significantly associated with TE, SE, and SY constitution types, respectively. From the functional relationship analysis using all loci with a p-value≤10−4, genes associated with each constitution type were identified. Fifteen (15) genes, including GPM6A, SYT4, and GRIK1, were significantly associated with the TE constitution type (p<0.05); 12 genes, including DRGX and AKAP11, were significantly associated with the SE constitution type (p<0.05); and 17 genes, including ZFP42, CDH22, ALDH1A2, OTX2, and EN2, were significantly associated with the SY constitution type (p<0.05). Conclusions Genetic loci and genes associated with Sasang constitution types were systematically identified from a genome-wide association study using a large number of subjects. PMID:22394158

  3. Population structure and covariate analysis based on pairwise microsatellite allele matching frequencies.

    PubMed

    Givens, Geof H; Ozaksoy, Isin

    2007-01-01

    We describe a general model for pairwise microsatellite allele matching probabilities. The model can be used for analysis of population substructure, and is particularly focused on relating genetic correlation to measurable covariates. The approach is intended for cases when the existence of subpopulations is uncertain and a priori assignment of samples to hypothesized subpopulations is difficult. Such a situation arises, for example, with western Arctic bowhead whales, where genetic samples are available only from a possibly mixed migratory assemblage. We estimate genetic structure associated with spatial, temporal, or other variables that may confound the detection of population structure. In the bowhead case, the model permits detection of genetic patterns associated with a temporally pulsed multi-population assemblage in the annual migration. Hypothesis tests for population substructure and for covariate effects can be carried out using permutation methods. Simulated and real examples illustrate the effectiveness and reliability of the approach and enable comparisons with other familiar approaches. Analysis of the bowhead data finds no evidence for two temporally pulsed subpopulations using the best available data, although a significant pattern found by other researchers using preliminary data is also confirmed here. Code in the R language is available from www.stat.colostate.edu/~geof/gammmp.html.

  4. Analysis of serotonin receptor 2A gene (HTR2A): association study with autism spectrum disorder in the Indian population and investigation of the gene expression in peripheral blood leukocytes.

    PubMed

    Guhathakurta, Subhrangshu; Singh, Asem Surindro; Sinha, Swagata; Chatterjee, Anindita; Ahmed, Shabina; Ghosh, Saurabh; Usha, Rajamma

    2009-12-01

    Several studies suggest involvement of serotoninergic system in the pathophysiology of Autism Spectrum Disorder (ASD). The 5-HT receptor binding studies using (3)H-lysergic acid diethylamide ((3)H-LSD) and linkage analysis provided evidences to consider HTR2A as a potential candidate gene for ASD. The three SNPs, -1438A/G (rs6311), 102T/C (rs6313) and 1354C/T (rs6314) of HTR2A have been well studied in the etiology of various neuropsychiatric disorders. But studies on association of this gene with ASD are limited to two reports from American and Korean populations. Additionally there are reports, which demonstrated paternal imprinting of HTR2A with expression from only one allele. So far no reports are available on HTR2A and its association with any neuropsychiatric disorders from Indian population. Therefore, the present study investigates association of the above mentioned three markers of HTR2A with ASD in Indian population using population and family-based approaches. The study also deals with allelic expression pattern of HTR2A in Peripheral Blood Leukocytes (PBLs) to understand the parental imprinting status. The genotyping analyses were carried out for probands, parents and controls. The subsequent association analyses did not show association of these markers with ASD. So, HTR2A is unlikely to be a genetic marker for ASD in Indian population. The expression analyses showed absence of monoallelic expression, suggesting lack of parental imprinting of HTR2A gene. However, we noticed methylation of the CpG sites at -1438A/G and 102T/C loci of HTR2A gene. Further bioinformatics analysis revealed absence of CpG islands in the promoter of the gene supporting biallelic expression pattern of HTR2A in PBLs.

  5. Worry about breast cancer recurrence: a population-based analysis.

    PubMed

    Tewari, Apoorva; Chagpar, Anees B

    2014-07-01

    As more patients with breast cancer survive treatment, the importance of their long-term quality of life is increasing. One important concern for many survivors is fear of recurrence. To better understand worry about recurrence, we conducted a population-based statistical analysis. The National Health Interview Survey (NHIS) is the largest annual source of health information for the U.S. population. We obtained data from the 2010 survey, which asked breast cancer survivors about their fear of recurrence and quality of life. Data were analyzed using SUDAAN software. The 2010 NHIS sample represented 2,668,697 breast cancer survivors. On univariate analysis, worry about recurrence was correlated with current age (P = 0.03) and radiation therapy (P = 0.04). Worry was strongly associated with perceived risk of recurrence (P < 0.01) and decreased overall quality of life (P < 0.01) as well as lower self-reported physical (P < 0.01) and mental (P < 0.01) health and poor satisfaction with social activities and relationships (P < 0.01). On multivariate analysis, worry was not independently associated with decreased quality of life (P = 0.09). However, those who "always worried" about recurrence had a lower quality of life (odds ratio, 0.06; 95% confidence interval, 0.01 to 0.45). Worry about recurrence among breast cancer survivors is associated with age and radiation therapy and is correlated with self-reported physical health, mental health, social relationships, and overall quality of life. It is a significant predictor of decreased quality of life in those who worry the most. Screening for worry about recurrence is an important measure for the improvement of quality of life among breast cancer survivors.

  6. Association between RTEL1 gene polymorphisms and COPD susceptibility in a Chinese Han population.

    PubMed

    Ding, Yipeng; Xu, Heping; Yao, Jinjian; Xu, Dongchuan; He, Ping; Yi, Shengyang; Li, Quanni; Liu, Yuanshui; Wu, Cibing; Tian, Zhongjie

    2017-01-01

    We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 ( RTEL1 ), which has been associated with telomere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population. In a case-control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10-0.82; P =0.02). In the genetic model analysis, we found that the "C/C" genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13-0.86; P =0.022) and recessive model (OR =0.32; 95% CI =0.12-0.80; P =0.009). Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population.

  7. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

    PubMed

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J; Krueger, Gerald G; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T S; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L; Qureshi, Abrar A; de Bakker, Paul I W; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-04-23

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

  8. Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

    PubMed Central

    Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T. S.; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L.; Qureshi, Abrar A.; de Bakker, Paul I. W.; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

    2015-01-01

    Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations. PMID:25903422

  9. Genetic analysis reveals demographic fragmentation of grizzly bears yielding vulnerably small populations

    PubMed Central

    Proctor, Michael F; McLellan, Bruce N; Strobeck, Curtis; Barclay, Robert M.R

    2005-01-01

    Ecosystem conservation requires the presence of native carnivores, yet in North America, the distributions of many larger carnivores have contracted. Large carnivores live at low densities and require large areas to thrive at the population level. Therefore, if human-dominated landscapes fragment remaining carnivore populations, small and demographically vulnerable populations may result. Grizzly bear range contraction in the conterminous USA has left four fragmented populations, three of which remain along the Canada–USA border. A tenet of grizzly bear conservation is that the viability of these populations requires demographic linkage (i.e. inter-population movement of both sexes) to Canadian bears. Using individual-based genetic analysis, our results suggest this demographic connection has been severed across their entire range in southern Canada by a highway and associated settlements, limiting female and reducing male movement. Two resulting populations are vulnerably small (≤100 animals) and one of these is completely isolated. Our results suggest that these trans-border bear populations may be more threatened than previously thought and that conservation efforts must expand to include international connectivity management. They also demonstrate the ability of genetic analysis to detect gender-specific demographic population fragmentation in recently disturbed systems, a traditionally intractable yet increasingly important ecological measurement worldwide. PMID:16243699

  10. Genetic analysis reveals demographic fragmentation of grizzly bears yielding vulnerably small populations.

    PubMed

    Proctor, Michael F; McLellan, Bruce N; Strobeck, Curtis; Barclay, Robert M R

    2005-11-22

    Ecosystem conservation requires the presence of native carnivores, yet in North America, the distributions of many larger carnivores have contracted. Large carnivores live at low densities and require large areas to thrive at the population level. Therefore, if human-dominated landscapes fragment remaining carnivore populations, small and demographically vulnerable populations may result. Grizzly bear range contraction in the conterminous USA has left four fragmented populations, three of which remain along the Canada-USA border. A tenet of grizzly bear conservation is that the viability of these populations requires demographic linkage (i.e. inter-population movement of both sexes) to Canadian bears. Using individual-based genetic analysis, our results suggest this demographic connection has been severed across their entire range in southern Canada by a highway and associated settlements, limiting female and reducing male movement. Two resulting populations are vulnerably small (< or =100 animals) and one of these is completely isolated. Our results suggest that these trans-border bear populations may be more threatened than previously thought and that conservation efforts must expand to include international connectivity management. They also demonstrate the ability of genetic analysis to detect gender-specific demographic population fragmentation in recently disturbed systems, a traditionally intractable yet increasingly important ecological measurement worldwide.

  11. Comparative analysis of the frequency, distribution and population sizes of yeasts associated with canine seborrheic dermatitis and healthy skin.

    PubMed

    Yurayart, Chompoonek; Chindamporn, Ariya; Suradhat, Sanipa; Tummaruk, Padet; Kajiwara, Susumu; Prapasarakul, Nuvee

    2011-03-24

    The purpose of this study was to investigate the diversity of yeast associated with the degree of canine seborrheic dermatitis (SD) by anatomical sites. Fifty-seven samples were divided as 17 healthy skin, 20 with primary seborrheic dermatitis (PSD), and 20 with secondary seborrheic dermatitis (SSD). Yeast isolation and characterization were carried out based on microscopical features and biochemical properties. DNA analysis at the internal transcribed spacer I of 26S rDNA region was utilized for species confirmation. Four species of yeast consisting Malassezia pachydermatis, Malassezia furfur, Candida parapsilosis and Candida tropicalis recovered from examined dogs. M. pachydermatis and C. parapsilosis were isolated from all dogs, but C. tropicalis and M. furfur were recovered from 3 healthy dogs and one diseased dog, respectively. The number of M. pachydermatis and C. parapsilosis in diseased dogs was higher than that of healthy specimens (P<0.01). High frequency and population size of C. parapsilosis were closely associated to PSD, while those of M. pachydermatis were associated with both PSD and SSD (P<0.01). C. parapsilosis were predominant at the perianal area. This study demonstrated the co-colonization of M. pachydermatis and C. parapsilosis in large amounts and frequency associated with stage of disease and anatomical site. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Epigenetic associations of type 2 diabetes and BMI in an Arab population.

    PubMed

    Al Muftah, Wadha A; Al-Shafai, Mashael; Zaghlool, Shaza B; Visconti, Alessia; Tsai, Pei-Chien; Kumar, Pankaj; Spector, Tim; Bell, Jordana; Falchi, Mario; Suhre, Karsten

    2016-01-01

    The prevalence of type 2 diabetes (T2D) and obesity has dramatically increased within a few generations, reaching epidemic levels. In addition to genetic risk factors, epigenetic mechanisms triggered by changing environment are investigated for their role in the pathogenesis of these complex diseases. Epigenome-wide association studies (EWASs) have revealed significant associations of T2D, obesity, and BMI with DNA methylation. However, populations from the Middle East, where T2D and obesity rates are highest worldwide, have not been investigated so far. We performed the first EWAS in an Arab population with T2D and BMI and attempted to replicate 47 EWAS associations previously reported in Caucasians. We used the Illumina Infinium HumanMethylation450 BeadChip to quantify DNA methylation in whole blood DNA from 123 subjects of 15 multigenerational families from Qatar. To investigate the effect of differing genetic background and environment on the epigenetic associations, we further assessed the effect of replicated loci in 810 twins from UK. Our EWAS suggested a novel association between T2D and cg06721411 (DQX1; p value = 1.18 × 10(-9)). We replicated in the Qatari population seven CpG associations with BMI (SOCS3, p value = 3.99 × 10(-6); SREBF1, p value = 4.33 × 10(-5); SBNO2, p value = 5.87 × 10(-5); CPT1A, p value = 7.99 × 10(-5); PRR5L, p value = 1.85 × 10(-4); cg03078551, intergenic region on chromosome 17; p value = 1.00 × 10(-3); LY6G6E, p value = 1.10 × 10(-3)) and one with T2D (TXNIP, p value = 2.46 × 10(-5)). All the associations were further confirmed in the UK cohort for both BMI and T2D. Meta-analysis increased the significance of the observed associations and revealed strong heterogeneity of the effect sizes (apart from CPT1A), although associations at these loci showed concordant direction in the two populations. Our study replicated eight known CpG associations with T

  13. A practical guide to environmental association analysis in landscape genomics.

    PubMed

    Rellstab, Christian; Gugerli, Felix; Eckert, Andrew J; Hancock, Angela M; Holderegger, Rolf

    2015-09-01

    Landscape genomics is an emerging research field that aims to identify the environmental factors that shape adaptive genetic variation and the gene variants that drive local adaptation. Its development has been facilitated by next-generation sequencing, which allows for screening thousands to millions of single nucleotide polymorphisms in many individuals and populations at reasonable costs. In parallel, data sets describing environmental factors have greatly improved and increasingly become publicly accessible. Accordingly, numerous analytical methods for environmental association studies have been developed. Environmental association analysis identifies genetic variants associated with particular environmental factors and has the potential to uncover adaptive patterns that are not discovered by traditional tests for the detection of outlier loci based on population genetic differentiation. We review methods for conducting environmental association analysis including categorical tests, logistic regressions, matrix correlations, general linear models and mixed effects models. We discuss the advantages and disadvantages of different approaches, provide a list of dedicated software packages and their specific properties, and stress the importance of incorporating neutral genetic structure in the analysis. We also touch on additional important aspects such as sampling design, environmental data preparation, pooled and reduced-representation sequencing, candidate-gene approaches, linearity of allele-environment associations and the combination of environmental association analyses with traditional outlier detection tests. We conclude by summarizing expected future directions in the field, such as the extension of statistical approaches, environmental association analysis for ecological gene annotation, and the need for replication and post hoc validation studies. © 2015 John Wiley & Sons Ltd.

  14. Genome-wide copy number variation analysis identified deletions in SFMBT1 associated with fasting plasma glucose in a Han Chinese population.

    PubMed

    Chung, Ren-Hua; Chiu, Yen-Feng; Hung, Yi-Jen; Lee, Wen-Jane; Wu, Kwan-Dun; Chen, Hui-Ling; Lin, Ming-Wei; Chen, Yii-Der I; Quertermous, Thomas; Hsiung, Chao A

    2017-08-08

    Fasting glucose and fasting insulin are glycemic traits closely related to diabetes, and understanding the role of genetic factors in these traits can help reveal the etiology of type 2 diabetes. Although single nucleotide polymorphisms (SNPs) in several candidate genes have been found to be associated with fasting glucose and fasting insulin, copy number variations (CNVs), which have been reported to be associated with several complex traits, have not been reported for association with these two traits. We aimed to identify CNVs associated with fasting glucose and fasting insulin. We conducted a genome-wide CNV association analysis for fasting plasma glucose (FPG) and fasting plasma insulin (FPI) using a family-based genome-wide association study sample from a Han Chinese population in Taiwan. A family-based CNV association test was developed in this study to identify common CNVs (i.e., CNVs with frequencies ≥ 5%), and a generalized estimating equation approach was used to test the associations between the traits and counts of global rare CNVs (i.e., CNVs with frequencies <5%). We found a significant genome-wide association for common deletions with a frequency of 5.2% in the Scm-like with four mbt domains 1 (SFMBT1) gene with FPG (association p-value = 2×10 -4 and an adjusted p-value = 0.0478 for multiple testing). No significant association was observed between global rare CNVs and FPG or FPI. The deletions in 20 individuals with DNA samples available were successfully validated using PCR-based amplification. The association of the deletions in SFMBT1 with FPG was further evaluated using an independent population-based replication sample obtained from the Taiwan Biobank. An association p-value of 0.065, which was close to the significance level of 0.05, for FPG was obtained by testing 9 individuals with CNVs in the SFMBT1 gene region and 11,692 individuals with normal copies in the replication cohort. Previous studies have found that SNPs in SFMBT1 are

  15. Genetic diversity of disease-associated loci in Turkish population.

    PubMed

    Karaca, Sefayet; Cesuroglu, Tomris; Karaca, Mehmet; Erge, Sema; Polimanti, Renato

    2015-04-01

    Many consortia and international projects have investigated the human genetic variation of a large number of ethno-geographic groups. However, populations with peculiar genetic features, such as the Turkish population, are still absent in publically available datasets. To explore the genetic predisposition to health-related traits of the Turkish population, we analyzed 34 genes associated with different health-related traits (for example, lipid metabolism, cardio-vascular diseases, hormone metabolism, cellular detoxification, aging and energy metabolism). We observed relevant differences between the Turkish population and populations with non-European ancestries (that is, Africa and East Asia) in some of the investigated genes (that is, AGT, APOE, CYP1B1, GNB3, IL10, IL6, LIPC and PON1). As most complex traits are highly polygenic, we developed polygenic scores associated with different health-related traits to explore the genetic diversity of the Turkish population with respect to other human groups. This approach showed significant differences between the Turkish population and populations with non-European ancestries, as well as between Turkish and Northern European individuals. This last finding is in agreement with the genetic structure of European and Middle East populations, and may also agree with epidemiological evidences about the health disparities of Turkish communities in Northern European countries.

  16. Study of risk factors for gastric cancer by populational databases analysis

    PubMed Central

    Ferrari, Fangio; Reis, Marco Antonio Moura

    2013-01-01

    AIM: To study the association between the incidence of gastric cancer and populational exposure to risk/protective factors through an analysis of international databases. METHODS: Open-access global databases concerning the incidence of gastric cancer and its risk/protective factors were identified through an extensive search on the Web. As its distribution was neither normal nor symmetric, the cancer incidence of each country was categorized according to ranges of percentile distribution. The association of each risk/protective factor with exposure was measured between the extreme ranges of the incidence of gastric cancer (under the 25th percentile and above the 75th percentile) by the use of the Mann-Whitney test, considering a significance level of 0.05. RESULTS: A variable amount of data omission was observed among all of the factors under study. A weak or nonexistent correlation between the incidence of gastric cancer and the study variables was shown by a visual analysis of scatterplot dispersion. In contrast, an analysis of categorized incidence revealed that the countries with the highest human development index (HDI) values had the highest rates of obesity in males and the highest consumption of alcohol, tobacco, fruits, vegetables and meat, which were associated with higher incidences of gastric cancer. There was no significant difference for the risk factors of obesity in females and fish consumption. CONCLUSION: Higher HDI values, coupled with a higher prevalence of male obesity and a higher per capita consumption of alcohol, tobacco, fruits, vegetables and meat, are associated with a higher incidence of gastric cancer based on an analysis of populational global data. PMID:24409066

  17. Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis.

    PubMed

    Wang, Feng; Han, Lili; Hu, Dayi

    2017-01-01

    Studies on the association of fasting insulin concentrations or insulin resistance with subsequent risk of hypertension have yielded conflicting results. To quantitatively assess the association of fasting insulin concentrations or homeostasis model assessment insulin resistance (HOMA-IR) with incident hypertension in a general population by performing a meta-analysis. We searched the PubMed and Embase databases until August 31, 2016 for prospective observational studies investigating the elevated fasting insulin concentrations or HOMA-IR with subsequent risk of hypertension in the general population. Pooled risk ratio (RR) and 95% confidence interval (CI) of hypertension was calculated for the highest versus the lowest category of fasting insulin or HOMA-IR. Eleven studies involving 10,230 hypertension cases were identified from 55,059 participants. Meta-analysis showed that the pooled adjusted RR of hypertension was 1.54 (95% CI 1.34-1.76) for fasting insulin concentrations and 1.43 (95% CI 1.27-1.62) for HOMA-IR comparing the highest to the lowest category. Subgroup analysis results showed that the association of fasting insulin concentrations with subsequent risk of hypertension seemed more pronounced in women (RR 2.07; 95% CI 1.19-3.60) than in men (RR 1.48; 95% CI 1.17-1.88). This meta-analysis suggests that elevated fasting insulin concentrations or insulin resistance as estimated by homeostasis model assessment is independently associated with an exacerbated risk of hypertension in the general population. Early intervention of hyperinsulinemia or insulin resistance may help clinicians to identify the high risk of hypertensive population. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study.

    PubMed

    Hardi, Hanaa; Melki, Rahma; Boughaleb, Zouhour; El Harroudi, Tijani; Aissaoui, Souria; Boukhatem, Noureddine

    2018-03-15

    Genetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population. We genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses. ERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34-6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17-5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected. Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction. Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7-8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and

  19. Leveraging Hierarchical Population Structure in Discrete Association Studies

    PubMed Central

    Carlson, Jonathan; Kadie, Carl; Mallal, Simon; Heckerman, David

    2007-01-01

    Population structure can confound the identification of correlations in biological data. Such confounding has been recognized in multiple biological disciplines, resulting in a disparate collection of proposed solutions. We examine several methods that correct for confounding on discrete data with hierarchical population structure and identify two distinct confounding processes, which we call coevolution and conditional influence. We describe these processes in terms of generative models and show that these generative models can be used to correct for the confounding effects. Finally, we apply the models to three applications: identification of escape mutations in HIV-1 in response to specific HLA-mediated immune pressure, prediction of coevolving residues in an HIV-1 peptide, and a search for genotypes that are associated with bacterial resistance traits in Arabidopsis thaliana. We show that coevolution is a better description of confounding in some applications and conditional influence is better in others. That is, we show that no single method is best for addressing all forms of confounding. Analysis tools based on these models are available on the internet as both web based applications and downloadable source code at http://atom.research.microsoft.com/bio/phylod.aspx. PMID:17611623

  20. Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions.

    PubMed

    Zoldoš, Vlatka; Biruš, Ivan; Muratovic, Edina; Šatovic, Zlatko; Vojta, Aleksandar; Robin, Odile; Pustahija, Fatima; Bogunic, Faruk; Vicic Bockor, Vedrana; Siljak-Yakovlev, Sonja

    2018-01-01

    Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpentine soil. Amplified fragment length polymorphism and methylation-sensitive amplification polymorphism analyses revealed that the three populations did not differentiate genetically, but were clearly separated in three distinct clusters according to DNA methylation profiles. Principal coordinate analysis showed that overall epigenetic variation was closely related to habitat conditions. A new methylation-sensitive amplification polymorphism scoring approach allowed identification of mainly unmethylated (φST = 0.190) and fully CpG methylated (φST = 0.118) subepiloci playing a role in overall population differentiation, in comparison with hemimethylated sites (φST = 0.073). In addition, unusual rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were recorded in the population growing on serpentine soil, suggesting dynamic chromosome rearrangements probably linked to global genome demethylation, which might have reactivated some mobile elements. We discuss our results considering our earlier data on morphology and leaf anatomy of several L. bosniacum populations, and suggest a possible role of epigenetics as a key element in population differentiation associated with environmental stress in these particular lily populations. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Short-term population-based non-linear concentration-response associations between fine particulate matter and respiratory diseases in Taipei (Taiwan): a spatiotemporal analysis.

    PubMed

    Yu, Hwa-Lung; Chien, Lung-Chang

    2016-01-01

    Fine particulate matter <2.5 μm (PM2.5) has been associated with human health issues; however, findings regarding the influence of PM2.5 on respiratory disease remain inconsistent. The short-term, population-based association between the respiratory clinic visits of children and PM2.5 exposure levels were investigated by considering both the spatiotemporal distributions of ambient pollution and clinic visit data. We applied a spatiotemporal structured additive regression model to examine the concentration-response (C-R) association between children's respiratory clinic visits and PM2.5 concentrations. This analysis was separately performed on three respiratory disease categories that were selected from the Taiwanese National Health Insurance database, which includes 41 districts in the Taipei area of Taiwan from 2005 to 2007. The findings reveal a non-linear C-R pattern of PM2.5, particularly in acute respiratory infections. However, a PM2.5 increase at relatively lower levels can elevate the same-day respiratory health risks of both preschool children (<6 years old) and schoolchildren (6-14 years old). In preschool children, same-day health risks rise when concentrations increase from 0.76 to 7.44 μg/m(3), and in schoolchildren, same-day health risks rise when concentrations increase from 0.76 to 7.52 μg/m(3). Changes in PM2.5 levels generally exhibited no significant association with same-day respiratory risks, except in instances where PM2.5 levels are extremely high, and these occurrences do exhibit a significant positive influence on respiratory health that is especially notable in schoolchildren. A significant high relative rate of respiratory clinic visits are concentrated in highly populated areas. We highlight the non-linearity of the respiratory health effects of PM2.5 on children to investigate this population-based association. The C-R relationship in this study can provide a highly valuable alternative for assessing the effects of ambient air

  2. Saitohin Q7R polymorphism is associated with late-onset Alzheimer's disease susceptibility among caucasian populations: a meta-analysis.

    PubMed

    Huang, Rong; Tian, Sai; Cai, Rongrong; Sun, Jie; Xia, Wenqing; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2017-08-01

    Saitohin (STH) Q7R polymorphism has been reported to influence the individual's susceptibility to Alzheimer's disease (AD); however, conclusions remain controversial. Therefore, we performed this meta-analysis to explore the association between STH Q7R polymorphism and AD risk. Systematic literature searches were performed in the PubMed, Embase, Cochrane Library and Web of Science for studies published before 31 August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association using a fixed- or random-effects model. Subgroup analyses, Galbraith plot and sensitivity analyses were also performed. All statistical analyses were performed with STATA Version 12.0. A total of 19 case-control studies from 17 publications with 4387 cases and 3972 controls were included in our meta-analysis. The results showed that the Q7R polymorphism was significantly associated with an increased risk of AD in a recessive model (RR versus QQ+QR, OR = 1.27, 95% CI = 1.01-1.60, P = 0.040). After excluding the four studies not carried out in caucasians, the overall association was unchanged in all comparison models. Further subgroup analyses stratified by the time of AD onset, and the quality of included studies provided statistical evidence of significant increased risk of AD in RR versus QQ+QR model only in late-onset subjects (OR = 1.56, 95% CI = 1.07-2.26, P = 0.021) and in studies with high quality (OR = 1.37, 95% CI = 1.01-1.86, P = 0.043). This meta-analysis suggests that the RR genotype in saitohin Q7R polymorphism may be a human-specific risk factor for AD, especially among late-onset AD subjects and caucasian populations. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Factors associated with early marijuana initiation in a criminal justice population.

    PubMed

    Savage, Rebekah J; King, Vinetra L; Clark, C Brendan; Cropsey, Karen L

    2017-01-01

    Initiation of marijuana during adolescence is associated with negative outcomes and is more common among those with criminal justice involvement. We sought to determine demographics, psychosocial factors, mental health factors, and criminal outcomes associated with earlier age at first marijuana use in a criminal justice population. Data from structured, in-person interviews of adults in a criminal corrections program were analyzed. Participants (689 men and women ages 19 and older) were recruited for a larger smoking cessation trial (2009-2013) as a volunteer sample by flyers at a community corrections site. 516 had smoked both nicotine and marijuana and were included in the analysis. We determined associations between self-reported age at first marijuana use and sex, race, income, educational attainment, history of abuse, family problems, psychiatric problems, criminal record, and age of nicotine and alcohol initiation. Of 516 participants, 68% were men, and 64.5% were Black. No participants were of Hispanic ethnicity. Average age of marijuana initiation was 15.1years (SD 3.7years). After linear regression, earlier age at marijuana initiation was associated with male sex and more criminal offenses (person/violent and court). Race and psychiatric problems were not associated with earlier marijuana initiation. Earlier adolescent marijuana initiation is associated with more criminal offenses in a criminal justice population. Men initiate marijuana earlier than women. Adolescents at high risk of justice involvement may benefit from delayed initiation of marijuana, specifically men. Additional studies should examine prevention strategies for adolescent marijuana use that target those at highest risk. Copyright © 2016. Published by Elsevier Ltd.

  4. Ancestry estimation and control of population stratification for sequence-based association studies.

    PubMed

    Wang, Chaolong; Zhan, Xiaowei; Bragg-Gresham, Jennifer; Kang, Hyun Min; Stambolian, Dwight; Chew, Emily Y; Branham, Kari E; Heckenlively, John; Fulton, Robert; Wilson, Richard K; Mardis, Elaine R; Lin, Xihong; Swaroop, Anand; Zöllner, Sebastian; Abecasis, Gonçalo R

    2014-04-01

    Estimating individual ancestry is important in genetic association studies where population structure leads to false positive signals, although assigning ancestry remains challenging with targeted sequence data. We propose a new method for the accurate estimation of individual genetic ancestry, based on direct analysis of off-target sequence reads, and implement our method in the publicly available LASER software. We validate the method using simulated and empirical data and show that the method can accurately infer worldwide continental ancestry when used with sequencing data sets with whole-genome shotgun coverage as low as 0.001×. For estimates of fine-scale ancestry within Europe, the method performs well with coverage of 0.1×. On an even finer scale, the method improves discrimination between exome-sequenced study participants originating from different provinces within Finland. Finally, we show that our method can be used to improve case-control matching in genetic association studies and to reduce the risk of spurious findings due to population structure.

  5. Cluster headache and the hypocretin receptor 2 reconsidered: a genetic association study and meta-analysis.

    PubMed

    Weller, Claudia M; Wilbrink, Leopoldine A; Houwing-Duistermaat, Jeanine J; Koelewijn, Stephany C; Vijfhuizen, Lisanne S; Haan, Joost; Ferrari, Michel D; Terwindt, Gisela M; van den Maagdenberg, Arn M J M; de Vries, Boukje

    2015-08-01

    Cluster headache is a severe neurological disorder with a complex genetic background. A missense single nucleotide polymorphism (rs2653349; p.Ile308Val) in the HCRTR2 gene that encodes the hypocretin receptor 2 is the only genetic factor that is reported to be associated with cluster headache in different studies. However, as there are conflicting results between studies, we re-evaluated its role in cluster headache. We performed a genetic association analysis for rs2653349 in our large Leiden University Cluster headache Analysis (LUCA) program study population. Systematic selection of the literature yielded three additional studies comprising five study populations, which were included in our meta-analysis. Data were extracted according to predefined criteria. A total of 575 cluster headache patients from our LUCA study and 874 controls were genotyped for HCRTR2 SNP rs2653349 but no significant association with cluster headache was found (odds ratio 0.91 (95% confidence intervals 0.75-1.10), p = 0.319). In contrast, the meta-analysis that included in total 1167 cluster headache cases and 1618 controls from the six study populations, which were part of four different studies, showed association of the single nucleotide polymorphism with cluster headache (random effect odds ratio 0.69 (95% confidence intervals 0.53-0.90), p = 0.006). The association became weaker, as the odds ratio increased to 0.80, when the meta-analysis was repeated without the initial single South European study with the largest effect size. Although we did not find evidence for association of rs2653349 in our LUCA study, which is the largest investigated study population thus far, our meta-analysis provides genetic evidence for a role of HCRTR2 in cluster headache. Regardless, we feel that the association should be interpreted with caution as meta-analyses with individual populations that have limited power have diminished validity. © International Headache Society 2014.

  6. Association of RTEL1 gene polymorphisms with stroke risk in a Chinese Han population

    PubMed Central

    Cai, Yi; Zeng, Chaosheng; Su, Qingjie; Zhou, Jingxia; Li, Pengxiang; Dai, Mingming; Wang, Desheng; Long, Faqing

    2017-01-01

    We investigated the associations between single nucleotide polymorphisms (SNPs) in the regulator of telomere elongation helicase 1 (RTEL1) gene and stroke in the Chinese population. A total of 400 stroke patients and 395 healthy participants were included in this study. Five SNPs in RTEL1 were genotyped and the association with stroke risk was analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to identify SNPs that correlated with stroke. Rs2297441 was associated with an increased risk of stroke in an allele model (odds ratio [OR] = 1.24, 95% confidence interval [95% CI] = 1.01–1.52, p = 0.043). Rs6089953 was associated with an increased risk of stroke under the genotype model ([OR] = 1.862, [CI] = 1.123–3.085, p = 0.016). Rs2297441 was associated with an increased risk of stroke in an additive model (OR = 1.234, 95% CI = 1.005, p = 0.045, Rs6089953, Rs6010620 and Rs6010621 were associated with an increased risk of stroke in the recessive model (Rs6089953:OR = 1.825, 95% CI = 1.121–2.969, p =0.01546; Rs6010620: OR = 1.64, 95% CI = 1.008–2.669, p =0.04656;Rs6010621:OR = 1.661, 95% CI = 1.014–2.722, p =0.04389). Our findings reveal a possible association between SNPs in the RTEL1 gene and stroke risk in Chinese population. PMID:29383136

  7. 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

  8. Association between coronary heart disease and erectile dysfunction in Chinese Han population

    PubMed Central

    Tian, Guo-Xiang; Li, Sheng; Liu, Tong-Zu; Zeng, Xian-Tao; Wei, Wan-Lin; Wang, Xing-Huan

    2017-01-01

    To investigate the association between coronary heart disease (CHD) and erectile dysfunction (ED) in Chinese Han population. Patients who went to the andrological out-patient clinic of our hospital between August 1, 2015 and May 1, 2016 and met all eligible criteria were enrolled in this study. The patients diagnosed as ED using self-administered International Index of Erectile Function-5 (IIEF-5) questionnaire were considered as case group and others were considered as control. The cases were categorized as mild, moderate, and severe ED. Subjects were interviewed for the history of CHD. Uni- and multivariate logistic regression models were used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using the SPSS 18.0 software. A total of 240 participants (56 ED patients and 184 controls) were enrolled. CHD prevalence was higher in cases without statistical significance (OR = 1.20, 95%CI = 0.63-2.29; p = 0.58). Results of adjusted analysis also showed a non-significantly increased risk (OR = 1.25, 95%CI = 0.55-2.85; p = 0.59). Stratified analysis by severity of ED revealed similar results. This study suggests no significant association exists between CHD and ED in Chinese Han population. PMID:28903442

  9. Association analysis of COMT/MTHFR polymorphisms and major depressive disorder in Chinese Han population.

    PubMed

    Shen, Xinhua; Wu, Yanfeng; Guan, Tiefeng; Wang, Xiaoquan; Qian, Mincai; Lin, Min; Shen, Zhongxia; Sun, Jushui; Zhong, Hua; Yang, Jianhong; Li, Liang; Yuan, Yonggui

    2014-06-01

    In several previous biochemical and genetic studies, the Val158Met polymorphism of the gene encoding catechol-O-methyltransferase (COMT) and the C677T polymorphism of Methylenetetrahydrofolate reductase (MTHFR) have been suggested to be involved in the pathogenesis as well as the treatment response of major depressive disorder (MDD), but the results have been inconsistent. In this study, we investigate the association of COMT/MTHFR and their interactions with MDD and antidepressant response in Chinese Han population. Three hundred and sixty eight depressed patients who met DSM-IV criteria for MDD were recruited for the study. Two hundred and nineteen normal controls were recruited from the local community. Patients and normal controls were genotyped for the functional COMT val158met and MTHFR C677T polymorphisms. Patients were characterized for clinical response to antidepressant treatment as measured by intra-individual changes of Hamilton Depression (HAMD-17) scores over 6 weeks. The T allele (OR=1.81; CI95%=1.40-2.34, P<0.001) and C/T genotype (OR=3.66; CI95% =2.53-5.28, P<0.001) of MTHFR C677T were significantly different between case and control groups. The COMT Met/Val genotype was more common among depressed individuals than among controls (OR=1.52, CI95%=1.04-2.21, P=0.02). There is disequilibrium in age and sex between case and control groups. Though we control the two variables in the statistic analysis, to be more accurate, we need to increase sample size in further study. Individuals with the genotype COMT Met/Val and MTHFR C/T have more probability of suffering from MDD. However, there is no association between gene polymorphism and treatment response. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations

    PubMed Central

    Cho, Eun Young; Jang, Yangsoo; Shin, Eun Soon; Jang, Hye Yoon; Yoo, Yeon-Kyeong; Kim, Sook; Jang, Ji Hyun; Lee, Ji Yeon; Yun, Min Hye; Park, Min Young; Chae, Jey Sook; Lim, Jin Woo; Shin, Dong Jik; Park, Sungha; Lee, Jong Ho; Han, Bok Ghee; Rae, Kim Hyung; Cardon, Lon R; Morris, Andrew P; Lee, Jong Eun; Clarke, Geraldine M

    2010-01-01

    Background Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. Methods The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. Results The association previously observed on chromosome 9p21 was independently replicated (p=3.08e–07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. Conclusion A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors. PMID:27325954

  11. Apolipoprotein M T-778C polymorphism is associated with serum lipid levels and the risk of coronary artery disease in the Chinese population: a meta-analysis.

    PubMed

    Zhang, Zhi; Chu, Guang; Yin, Rui-Xing

    2013-09-16

    The apolipoprotein M (APOM) T-778C gene polymorphism has been associated with serum lipid levels and the risk of coronary artery disease (CAD), but the results are inconclusive. The purpose of this meta-analysis was to detect the association between the APOM T-778C polymorphism and serum lipid levels and the risk of CAD in the Chinese population. Databases of MEDLINE, EMBASE, the Cochrane Library and CNKI were systematically searched. Data were extracted using standardized methods. The association was assessed by mean difference (MD) with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI. Ten studies with 4,413 patients were included in this meta-analysis. Pooled effects indicated that CT+CC group had higher levels of total cholesterol (TC) (MD:-0.36, 95% CI: -0.53 - -0.19, P < 0.0001) and low-density lipoprotein cholesterol (LDL-C) (MD: -0.08, 95% CI: -0.16 - -0.01, P = 0.03) than TT group. There was no difference in the levels of triglyceride (MD: 0.06, 95% CI: -0.04 - 0.15, P = 0.22) and high-density lipoprotein cholesterol (MD: 0.00, 95% CI: -0.03-0.03, P = 0.93) between TT and CT+CC groups. Pooled effects showed that CAD group had higher CT+CC genotype frequency than control group (OR: 1.97, 95% CI: 1.62-2.39, P < 0.00001; heterogeneity test x(2) = 2.96, P = 0.71, I(2) = 0%). The results of the current meta-analysis show that the CT+CC group has higher levels of TC and LDL-C than the TT group. Moreover, there is also a prominent association between APOM T-778C polymorphism and the risk of CAD in the Chinese population, the CT+CC genotype is associated with increased risk of CAD.

  12. No association between FOXP2 rs10447760 and schizophrenia in a replication study of the Chinese Han population.

    PubMed

    Yin, Jiajun; Jia, Ningren; Liu, Yansong; Jin, Chunhui; Zhang, Fuquan; Yu, Shui; Wang, Jun; Yuan, Jianmin

    2018-04-01

    Schizophrenia (SCZ) is a severe and heritable psychiatric disorder, and previous studies have shown that regulation of the forkhead-box P2 gene (FOXP2) may play a role in schizophrenia. Moreover, just a few studies have identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that was a risk variant for SCZ in the Chinese Han population. To examine whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a case-control study (1405 cases, 1137 controls) from China. We identified no association of rs10447760 in the FOXP2 gene with SCZ (all P>0.05). In addition, a meta-analysis indicated that the SNP rs10447760 was not associated with susceptibility to SCZ in Han Chinese populations (pooled odds ratio=1.44, 95% confidence interval: 0.63-3.31, P=0.39). Thus, our results did not support the association between FOXP2 rs10447760 and schizophrenia in a Chinese Han population, and large-scale genetic replication studies with different racial and geographic origins are required in the future.

  13. Genome-wide association analysis of ischemic stroke in young adults.

    PubMed

    Cheng, Yu-Ching; O'Connell, Jeffrey R; Cole, John W; Stine, O Colin; Dueker, Nicole; McArdle, Patrick F; Sparks, Mary J; Shen, Jess; Laurie, Cathy C; Nelson, Sarah; Doheny, Kimberly F; Ling, Hua; Pugh, Elizabeth W; Brott, Thomas G; Brown, Robert D; Meschia, James F; Nalls, Michael; Rich, Stephen S; Worrall, Bradford; Anderson, Christopher D; Biffi, Alessandro; Cortellini, Lynelle; Furie, Karen L; Rost, Natalia S; Rosand, Jonathan; Manolio, Teri A; Kittner, Steven J; Mitchell, Braxton D

    2011-11-01

    Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15-49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 × 10(-8)), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 × 10(-7)) and rs1986743 (in ARL6IP6; P = 2.7 × 10(-7)), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

  14. Association between Impulsivity and Weight Status in a General Population.

    PubMed

    Bénard, Marc; Camilleri, Géraldine M; Etilé, Fabrice; Méjean, Caroline; Bellisle, France; Reach, Gérard; Hercberg, Serge; Péneau, Sandrine

    2017-03-01

    The objective of this study is to examine the association between impulsivity and weight status in a large sample of the adult general population in France, and the influence of gender on this relationship. A total of 11,929 men and 39,114 women participating in the NutriNet-Santé cohort were selected in this cross-sectional analysis. The Barratt Impulsiveness Scale (BIS-11) was used to assess impulsivity. Weight and height were self-reported. The association between impulsivity and BMI was estimated using logistic regressions adjusted for socio-demographic and lifestyle factors. Individuals with high impulsivity levels (BIS-11 total score >71) were more likely to be obese (Odds Ratio (OR) = 1.80, 95% Confidence Interval (CI): 1.39, 2.33 in men; OR = 1.30, 95% CI: 1.15, 1.48 in women) compared to individuals in the average range of impulsivity. The strongest associations between impulsivity and obesity were observed in men, where highly impulsive participants were more likely to be class III obese (BMI > 40 kg/m²) (OR = 3.57, 95% CI: 1.86, 6.85). This large sample analysis supports the existence of a relationship between impulsivity and weight status and the importance of psychological factors in the prevention of obesity.

  15. Iron deficiency is associated with increased levels of blood cadmium in the Korean general population: Analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Byung-Kook; Kim, Yangho, E-mail: yanghokm@nuri.net

    Introduction: We present data from the Korean National Health and Nutrition Examination Survey 2008-2009 on the distribution of blood cadmium levels and their association with iron deficiency in a representative sample of the adult Korean population. Methods: Serum ferritin was categorized into three levels: low (serum ferritin <15.0 {mu}g/L), low normal (15.0-30.0 {mu}g/L for women and 15.0-50.0 for men), and normal ({>=}30.0 {mu}g/L for women and {>=}50.0 for men), and its association with blood cadmium level was assessed after adjustment for various demographic and lifestyle factors. Results: Geometric means of blood cadmium in the low serum ferritin group in women,more » men, and all participants were significantly higher than in the normal group. Additionally, multiple regression analysis after adjusting for various covariates showed that blood cadmium was significantly higher in the low-ferritin group in women, men, and all participants compared with the normal group. We also found an association between serum ferritin and blood cadmium among never-smoking participants. Discussion: We found, similar to other recent population-based studies, an association between iron deficiency and increased blood cadmium in men and women, independent of smoking status. The results of the present study show that iron deficiency is associated with increased levels of blood cadmium in the general population.« less

  16. Genome-wide association study reveals regions associated with gestation length in two pig populations.

    PubMed

    Hidalgo, A M; Lopes, M S; Harlizius, B; Bastiaansen, J W M

    2016-04-01

    Reproduction traits, such as gestation length (GLE), play an important role in dam line breeding in pigs. The objective of our study was to identify single nucleotide polymorphisms (SNPs) that are associated with GLE in two pig populations. Genotypes and deregressed breeding values were available for 2081 Dutch Landrace-based (DL) and 2301 Large White-based (LW) pigs. We identified two QTL regions for GLE, one in each population. For DL, three associated SNPs were detected in one QTL region spanning 0.52 Mbp on Sus scrofa chromosome (SSC) 2. For LW, four associated SNPs were detected in one region of 0.14 Mbp on SSC5. The region on SSC2 contains the heparin-binding EGF-like growth factor (HBEGF) gene, which promotes embryo implantation and has been described to be involved in embryo survival throughout gestation. The associated SNP can be used for marker-assisted selection in the studied populations, and further studies of the HBEGF gene are warranted to investigate its role in GLE. © 2015 Stichting International Foundation for Animal Genetics.

  17. Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

    PubMed

    Borgonio-Cuadra, Verónica Marusa; González-Huerta, Norma Celia; Rojas-Toledo, Emma Xochitl; Morales-Hernández, Eugenio; Pérez-Hernández, Nonanzit; Rodríguez-Pérez, José Manuel; Tovilla-Zárate, Carlos Alfonso; González-Castro, Thelma Beatriz; Hernández-Díaz, Yazmín; López-Narváez, María Lilia; Miranda-Duarte, Antonio

    2018-05-18

    Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

  18. Association between RTEL1 gene polymorphisms and COPD susceptibility in a Chinese Han population

    PubMed Central

    Ding, Yipeng; Xu, Heping; Yao, Jinjian; Xu, Dongchuan; He, Ping; Yi, Shengyang; Li, Quanni; Liu, Yuanshui; Wu, Cibing; Tian, Zhongjie

    2017-01-01

    Objective We investigated the association between single-nucleotide polymorphisms in regulation of telomere elongation helicase 1 (RTEL1), which has been associated with telomere length in several brain cancers and age-related diseases, and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese Han population. Methods In a case–control study that included 279 COPD cases and 290 healthy controls, five single-nucleotide polymorphisms in RTEL1 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. Results In the genotype model analysis, we determined that rs4809324 polymorphism had a decreased effect on the risk of COPD (CC versus TT: OR =0.28; 95% CI =0.10–0.82; P=0.02). In the genetic model analysis, we found that the “C/C” genotype of rs4809324 was associated with a decreased risk of COPD based on the codominant model (OR =0.33; 95% CI =0.13–0.86; P=0.022) and recessive model (OR =0.32; 95% CI =0.12–0.80; P=0.009). Conclusion Our data shed new light on the association between genetic polymorphisms of RTEL1 and COPD susceptibility in the Chinese Han population. PMID:28360516

  19. Factors associated with surgical management in an underinsured, safety net population.

    PubMed

    Winton, Lisa M; Nodora, Jesse N; Martinez, Maria Elena; Hsu, Chiu-Hsieh; Djenic, Brano; Bouton, Marcia E; Aristizabal, Paula; Ferguson, Elizabeth M; Weiss, Barry D; Komenaka, Ian K

    2016-02-01

    Few studies include significant numbers of racial and ethnic minority patients. The current study was performed to examine factors that affect breast cancer operations in an underinsured population. We performed a retrospective review of all breast cancer patients from January 2010 to May 2012. Patients with American Joint Committee on Cancer clinical stage 0-IIIA breast cancer underwent evaluation for type of operation: breast conservation, mastectomy alone, and reconstruction after mastectomy. The population included 403 patients with mean age 53 years. Twelve of the 50 patients (24%) diagnosed at stage IIIB presented with synchronous metastatic disease. Of the remaining patients, only 2 presented with metastatic disease (0.6%). The initial operation was 65% breast conservation, 26% mastectomy alone, and 10% reconstruction after mastectomy. Multivariate analysis revealed that Hispanic ethnicity (odds ratio [OR], 0.38; 95% CI, 0.19-0.73; P = .004), presentation with palpable mass (OR, 0.34; 95% CI, 0.13-0.90; P = .03), preoperative chemotherapy (OR, 0.25; 95% CI, 0.10-0.62; P = .003) were associated with a lesser likelihood of mastectomy. Multivariate analysis of factors associated with reconstruction after mastectomy showed that operation with Breast surgical oncologist (OR, 18.4; 95% CI, 2.18-155.14; P < .001) and adequate health literacy (OR, 3.13; 95% CI, 0.95-10.30; P = .06) were associated with reconstruction. The majority of safety net patients can undergo breast conservation despite delayed presentation and poor use of screening mammography. Preoperative chemotherapy increased the likelihood of breast conservation. Routine systemic workup in patients with operable breast cancer is not indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Fine-scale population structure of Malays in Peninsular Malaysia and Singapore and implications for association studies.

    PubMed

    Hoh, Boon-Peng; Deng, Lian; Julia-Ashazila, Mat Jusoh; Zuraihan, Zakaria; Nur-Hasnah, Ma'amor; Nur-Shafawati, Ab Rajab; Hatin, Wan Isa; Endom, Ismail; Zilfalil, Bin Alwi; Khalid, Yusoff; Xu, Shuhua

    2015-07-22

    Fine scale population structure of Malays - the major population in Malaysia, has not been well studied. This may have important implications for both evolutionary and medical studies. Here, we investigated the population sub-structure of Malay involving 431 samples collected from all states from peninsular Malaysia and Singapore. We identified two major clusters of individuals corresponding to the north and south peninsular Malaysia. On an even finer scale, the genetic coordinates of the geographical Malay populations are in correlation with the latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the pairwise FST of Malay sub-populations, of which the north and south regions showed the highest differentiation (FST [North-south] = 0.0011). The collective findings therefore suggest that population sub-structure of Malays are more heterogenous than previously expected even within a small geographical region, possibly due to factors like different genetic origins, geographical isolation, could result in spurious association as demonstrated in our analysis. We suggest that cautions should be taken during the stage of study design or interpreting the association signals in disease mapping studies which are expected to be conducted in Malay population in the near future.

  1. Association between osteoporosis and urinary calculus: evidence from a population-based study.

    PubMed

    Keller, J J; Lin, C-C; Kang, J-H; Lin, H-C

    2013-02-01

    This population-based case-control analysis investigated the association between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in detecting an association between osteoporosis and prior UC (adjusted odds ratio = 1.66). This association was consistent and significant regardless of stone location. UC has been demonstrated to be a risk factor for osteoporotic fractures, but no studies to date have directly investigated the association between UC and osteoporosis. This case-control analysis aimed to investigate the association of osteoporosis with prior UC using a population-based dataset in Taiwan. We first identified 39,840 cases ≥40 years who received their first-time diagnosis of osteoporosis between 2002 and 2009 and then randomly selected 79,680 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and the corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. The OR of having been previously diagnosed with UC for patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to controls after adjusting for geographic location, urbanization level, type I diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol abuse/alcohol dependence syndrome. The results consistently showed that osteoporosis was significantly associated with a previous diagnosis of UC regardless of stone location; the adjusted ORs of prior kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23-2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. This study succeeded in detecting an association between osteoporosis and prior UC. In addition

  2. Methylenetetrahydrofolate reductase polymorphisms and susceptibility to acute lymphoblastic leukemia in a Chinese population: a meta-analysis.

    PubMed

    Xiao, Yi; Deng, Tao-Ran; Su, Chang-Liang; Shang, Zhen

    2014-01-01

    Although many epidemiologic studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their association with acute lymphoblastic leukemia (ALL), definitive conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of ALL, a meta-analysis was performed in a Chinese population. A computerized literature search was carried out in PubMed, the Chinese Biomedicine (CBM) database, China National Knowledge Infrastructure (CNKI) platform, and the Wanfang database (Chinese) to collect relevant articles. A total of 11 articles including 1,738 ALL cases and 2,438 controls were included in this meta-analysis. Overall, a significantly decreased association was found between the MTHFR C677T polymorphism and ALL risk when all studies in Chinese populations were pooled into the meta-analysis. In subgroup analyses stratified by age, ethnicity, and source of controls, the same results were observed in children, in population-based studies, and in people with no stated ethnicity. However, a significantly increased association was also found for MTHFR C677T in hospital-based studies, and for MTHFR A1298C in people with no stated ethnicity. Our results suggest that the MTHFR C677T and A1298C polymorphisms may be potential biomarkers for ALL risk in Chinese populations, and studies with a larger sample size and wider population spectrum are required before definitive conclusions can be drawn. © 2014 S. Karger GmbH, Freiburg.

  3. Factors associated with post-ERCP pancreatitis and the effect of pancreatic duct stenting in a pediatric population.

    PubMed

    Troendle, David M; Abraham, Omana; Huang, Rong; Barth, Bradley A

    2015-01-01

    Risk factors for the development of post-ERCP pancreatitis (PEP) have not been identified in the pediatric population. It remains unclear what constitutes appropriate prophylaxis in this patient population. To assess the prevalence and severity of PEP in the pediatric population and identify factors associated with developing PEP and to evaluate the effect of prophylactic pancreatic duct stenting in high-risk patients. Retrospective analysis of an ERCP database at a single large pediatric center. Academic center. A total of 432 ERCPs performed on 313 patients younger than 19 years of age from January 2004 to October 2013. ERCP for any indication. Rates and severity of PEP, preprocedural and procedural risk factors for the development of PEP, and the effect of pancreatic stents on preventing PEP in high-risk patients. PEP occurred after 47 procedures (prevalence, 10.9%). Thirty-four cases were mild, 9 were moderate, and 4 were severe. There was no mortality. On multiple logistic analysis, pancreatic duct injection (P<.0001; odds ratio 30.8; 95% confidence interval [CI], 9.1-103.9) and pancreatic sphincterotomy (P<.01; OR 3.8; 95% CI, 1.6-9.8) were positively associated with PEP. A history of chronic pancreatitis was negatively associated with PEP (P<.05; OR 0.37; 95% CI, 0.15-0.93). On subset analysis, placing a prophylactic pancreatic stent was associated with significantly increased rates of PEP in patients with pancreatic duct injection compared with those who had no attempt at stent placement (P<.01). Two patients with severe pancreatitis had prophylactic pancreatic stents in place. Retrospective investigation. In the pediatric population, pancreatic duct injection and pancreatic sphincterotomy are associated with significantly increased rates of PEP, whereas a history of chronic pancreatitis is negatively associated. Prophylactic pancreatic stenting is associated with higher rates of PEP in high-risk patients and does not eliminate severe PEP. Copyright © 2015

  4. Sexual dimorphism is associated with population fitness in the seed beetle Callosobruchus maculatus.

    PubMed

    Rankin, Daniel J; Arnqvist, Göran

    2008-03-01

    The population consequences of sexual selection remain empirically unexplored. Comparative studies, involving extinction risk, have yielded different results as to the effect of sexual selection on population densities make contrasting predictions. Here, we investigate the relationship between sexual dimorphism (SD) and population productivity in the seed beetle Callosobruchus maculatus, using 13 populations that have evolved in isolation. Geometric morphometric methods and image analysis are employed to form integrative measures of sexual dimorphism, composed of variation in weight, size, body shape, and pigmentation. We found a positive relationship between SD and adult fitness (net adult offspring production) across our study populations, but failed to find any association between SD and juvenile fitness (egg-to-adult survival). Several mechanisms may have contributed to the pattern found, and variance in sexual selection regimes across populations, either in female choice for "good genes" or in the magnitude of direct benefits provided by their mates, would tend to produce the pattern seen. However, our results suggest that evolutionary constraints in the form of intralocus sexual conflict may have been the major generator of the relationship seen between SD and population fitness.

  5. Prevalence and associated factors of pinguecula in a rural population in Shanghai, Eastern China.

    PubMed

    Le, Qihua; Xiang, Jun; Cui, Xinhan; Zhou, Xiaodong; Xu, Jianjiang

    2015-04-01

    To determine the prevalence and associated factors of pinguecula in a rural Chinese population aged ≥ 50 years in Eastern China. This cross-sectional, population-based survey included an age-stratified random sample of 1108 residents living in Lvxiang Town of Jinshan District. Participants were requested to complete a comprehensive questionnaire to collect demographic data, history of systemic diseases and lifestyle details. The presence of pinguecula on slit lamp examination was recorded. The prevalence of pinguecula and its associated factors were investigated by logistic regression models. Among 1108 eligible subjects, 959 participated in the study, with an average age of 65.1 ± 9.2 years (range 50-89 years). The overall age-adjusted prevalence of pinguecula in this population was 75.57% (95% confidence interval 71.79-79.35%). Logistic regression analysis revealed that age (p = 0.002) and working outdoors (daily sunlight exposure ≥ 2 hours; p = 0.001) were independent risk factors for pinguecula. In addition, sex, education level, alcohol intake, smoking and decreased tear break-up time did not have associations with the development of pinguecula after adjusting for age and outdoor work occupations. The prevalence of pinguecula was 75.57% in this Chinese population aged ≥ 50 years from a coastal rural area of Shanghai, Eastern China, which was higher than the majority of previous findings. Age and working outdoors were independent risk factors for pinguecula.

  6. Association of common genetic variants with human skin color variation in Indian populations.

    PubMed

    Sarkar, Anujit; Nandineni, Madhusudan R

    2018-01-01

    Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ∼31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ∼19% of the variation observed in the samples. These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. © 2017 Wiley Periodicals, Inc.

  7. Association between MTHFR A1298C polymorphism and male infertility: A meta-analysis.

    PubMed

    Zhang, Qiang; Yin, Guo-Ying; Liu, Juan; Liang, Yue; Li, Yao-Yan; Zhao, Jing-Yu; Zhang, Li-Wen; Wang, Bai-Qi; Tang, Nai-Jun

    2017-04-01

    There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01-1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04-1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04-1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

  8. Association between edentulism and angina pectoris in Mexican adults aged 35 years and older: a multivariate analysis of a population-based survey.

    PubMed

    Medina-Solís, Carlo Eduardo; Pontigo-Loyola, América Patricia; Pérez-Campos, Eduardo; Hernández-Cruz, Pedro; Ávila-Burgos, Leticia; Kowolik, Michael J; Maupomé, Gerardo

    2014-03-01

    The possible association between oral infection and chronic inflammation and cardiovascular disease risk has been studied intensively. The present study is designed to determine the strength of association between edentulism and angina pectoris in Mexican adults aged 35 years and older. Using the tools and sampling strategies of the World Health Survey of the World Health Organization, cross-sectional data were collected in Mexico in the National Performance Assessment Survey (probabilistic, multistage, and cluster sampling). Dental information was available for 20 of the 32 states of Mexico. Angina and edentulism are self-reported in this study. Statistical analysis was performed using binary logistic regression adjusting for complex samples. A total of 13,966 participants, representing a population of 29,853,607 individuals, were included. Of the complete study population, 3,052,263 (10.2%) were completely toothless, and 673,810 (2.3%) were diagnosed with angina pectoris. After adjusting for smoking, alcohol consumption, diabetes, body mass index, and sex, the effect of edentulism on angina was modified by age (interaction), being more marked in the younger age group (odds ratio [OR] = exp(2.5597) =12.93) than in the older individuals surveyed (OR = exp(2.5597 + (-0.0334)) =12.51). Additionally, low physical activity (OR = 1.51; 95% confidence interval [CI] = 1.03 to 2.22) and higher socioeconomic status (OR = 1.37; 95% CI = 1.00 to 1.90) were more likely to be associated with angina pectoris. Overall, the results of this study, conducted in a representative sample of Mexican adults, suggest that an association exists between edentulism and angina pectoris. Additional studies are necessary to elucidate the underlying mechanism for this association.

  9. Main visual symptoms associated to refractive errors and spectacle need in a Brazilian population

    PubMed Central

    Schellini, Silvana; Ferraz, Fabio; Opromolla, Paula; Oliveira, Laryssa; Padovani, Carlos

    2016-01-01

    AIM To determine the main visual symptoms in a Brazilian population sample, associated to refractive errors (REs) and spectacle need to suggest priorities in preventive programs. METHODS A cross-sectional study was conducted in nine counties of the southeast region of Brazil, using a systematic sampling of households, between March 2004 and July 2005. The population was defined as individuals aged between 1 and 96y, inhabitants of 3600 residences to be evaluated and 3012 households were included, corresponding to 8010 subjects considered for participation in the survey, of whom 7654 underwent ophthalmic examinations. The individuals were evaluated according their demographic data, eye complaints and eye examination including the RE and the need to prescribe spectacles according to age. Statistical analysis was performed using SPSS software package and descriptive analysis using 95% confidence intervals (P<0.05). RESULTS The main symptom detected was asthenopia, most frequent in the 2nd and 3rd decades of life, with a significant decline after the 4th decade. Astigmatism was the RE most associated with asthenopia. Reduced near vision sight was more frequent in those ≥40y with a progressive decline thereafter. Spectacles were most frequently required in subjects of ≥40 years of age. CONCLUSION The main symptom related to the vision was asthenopia and was associated to astigmatism. The greatest need for spectacles prescription occurred after 40's, mainly to correct near vision. Subjects of ≥40 years old were determined to be at high risk of uncorrected REs. These observations can guide intervention programs for the Brazilian population. PMID:27990372

  10. Smoking is associated with increased resting energy expenditure in the general population: The NEO study.

    PubMed

    Blauw, Lisanne L; Boon, Mariëtte R; Rosendaal, Frits R; de Mutsert, Renée; Gast, Karin B; van Dijk, Ko Willems; Rensen, Patrick C N; Dekkers, Olaf M

    2015-11-01

    Animal studies and human studies in small selected populations have shown a positive association between nicotine smoking and resting energy expenditure (REE), but data in large cohorts are lacking. We aimed to investigate the association between smoking behavior and REE in a large, population-based study. Population-based cross-sectional study. In this cross-sectional analysis of baseline measurements from the Netherlands Epidemiology of Obesity (NEO) study (n=6673), we included participants with REE measurement by indirect calorimetry who were not using lipid or glucose lowering drugs (n=1189). We used linear regression analysis to examine the association of smoking status (never, former, occasional, current smoker) and smoking quantity (pack years) with REE per kilogram (kg) fat free mass (FFM) and with REE adjusted for FFM. Models were adjusted for age, sex, ethnicity, educational level, physical activity, energy intake and body mass index (BMI). Mean (standard deviation, SD) age was 55.2 (5.9) years and BMI was 26.3 (4.4) kg/m(2). 60% of the participants were women. Mean (SD) REE/FFM (kcal/day/kg FFM) was for male never smokers 25.1 (2.0), male current smokers 26.4 (2.8), female never smokers 28.9 (2.5) and female current smokers 30.1 (3.7). After adjustment, only current smokers had a higher REE/FFM (mean difference 1.28, 95% CI 0.64, 1.92), and a higher REE adjusted for FFM (mean difference 60.3 kcal/day, 95% CI 29.1, 91.5), compared with never smokers. There was no association between pack years and REE/FFM (mean difference -0.01, 95% CI -0.06, 0.04) or REE adjusted for FFM (mean difference 0.2, 95% CI -2.4, 2.8) in current smokers. Current smoking is associated with a higher resting energy expenditure compared with never smoking in a large population-based cohort. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinson, J.J.; Clegg, J.B.; Boyce, A.J.

    1994-09-01

    The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception ofmore » closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.« less

  12. The association of hyperglycaemia with prevalent tuberculosis: a population-based cross-sectional study.

    PubMed

    Bailey, Sarah Lou; Ayles, Helen; Beyers, Nulda; Godfrey-Faussett, Peter; Muyoyeta, Monde; du Toit, Elizabeth; Yudkin, John S; Floyd, Sian

    2016-12-05

    Systematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis. A population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia. Among 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11.1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration <11.1 mmol/L and also ≥11.1 mmol/L (2/405); corresponding figures for WC were 2 · 5% (272/11,045) and 4 · 0% (13/322). There was evidence for a positive linear association between hyperglycaemia and pulmonary prevalent tuberculosis. Taking a RBG cut-off 11.1 mmol/L, a combined analysis of data from Zambian and WC communities found evidence of association between hyperglycaemia and TB (adjusted odds ratio = 2 · 15, 95% CI [1 · 17-3 · 94]). The population attributable fraction of prevalent tuberculosis

  13. Association of educational status with heart rate recovery: a population-based propensity analysis.

    PubMed

    Shishehbor, Mehdi H; Baker, David W; Blackstone, Eugene H; Lauer, Michael S

    2002-12-01

    An abnormally attenuated heart rate recovery after exercise is a predictor of mortality that is thought to reflect decreased parasympathetic activity. Lower educational level may be associated with automatic imbalance. We sought to assess the association of educational level with heart rate recovery. Among 5246 healthy adults from a population-based cohort who underwent exercise testing, 874 (17%) did not graduate from high school, 1823 (35%) completed high school, and 2549 (49%) attended at least some college. An abnormal heart rate recovery was defined as a difference of associated with an abnormal heart rate recovery (OR = 1.9; 95% CI: 1.6 to 2.4; P <0.001). During 12-years of follow-up, there were 327 deaths. Poor educational status was associated with greater mortality (9% [80/874] vs. 6% [247/4372]; unadjusted hazard ratio [HR] = 1.9; 95% CI: 1.4 to 2.5; P <0.001). However, after accounting for age, sex, and heart rate recovery, educational status was a weaker predictor (HR = 1.3; 95% CI: 1.0 to 1.7). Educational status is independently associated with an abnormal heart rate recovery.

  14. Population and genomic lessons from genetic analysis of two Indian populations.

    PubMed

    Juyal, Garima; Mondal, Mayukh; Luisi, Pierre; Laayouni, Hafid; Sood, Ajit; Midha, Vandana; Heutink, Peter; Bertranpetit, Jaume; Thelma, B K; Casals, Ferran

    2014-10-01

    Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.

  15. Population Analysis: Communicating About Anthropometry in Context

    NASA Technical Reports Server (NTRS)

    Thaxton, Sherry; Rajulu, Sudhakar

    2009-01-01

    This slide presentation reviews the importance of communications about anthropometry and population analysis in particular for the design of aerospace systems. The difficulty of providing anthropometric accomodation an entire range of the population is reviewed, and the importance of communication of the issues with human system integration is emphasized, and the analysis of population as it applies to existing human factors methodologies is a novel way to assist with the communication. The issues of space suit design and anthropometry is reviewed as an example.

  16. Head circumference, leg length and its association with dementia among older adult population in Singapore.

    PubMed

    Chang, Sherilyn; Ong, Hui Lin; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Jeyagurunathan, Anitha; Shafie, Saleha; Mahendran, Rathi; Subramaniam, Mythily; Chong, Siow Ann

    2017-12-01

    Head circumference and leg length serve as reliable proxy indicators of early-life environment. Research studies have shown that these anthropometric measurements are associated with cognitive impairment and dementia among older adults. The aim of the present study was to assess the associations between dementia with head circumference and leg length among the older adult population in Singapore. This study also aimed to examine the sociodemographic correlates of these anthropometric measurements. Data were collected from 2565 older adults aged 60 years and above, in a population study on the Well-being of the Singapore Elderly. Head circumference and leg length measurements were obtained, and sociodemographic information was recorded. Dementia diagnosis was made using the 10/66 dementia algorithm. Anthropometric measurements were first stratified into quarters, and then logistic regression analysis was used to examine factors associated with head circumference and leg length, as well as to examine the association between dementia with these measurements. Sociodemographic correlates of head circumference and leg length include age, gender, ethnicity and education level. Smaller head circumference was independently associated with higher odds of 10/66 dementia (OR = 2.173-2.709). When the regression analysis was stratified by gender, the association was found only in the male sample. Leg length was not significantly associated with dementia after controlling for sociodemographic variables. Smaller head circumference is independently associated with dementia among older adults in Singapore. Findings from this study suggest that risk factors for dementia begin their influence in early life. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Rare-Variant Association Analysis: Study Designs and Statistical Tests

    PubMed Central

    Lee, Seunggeung; Abecasis, Gonçalo R.; Boehnke, Michael; Lin, Xihong

    2014-01-01

    Despite the extensive discovery of trait- and disease-associated common variants, much of the genetic contribution to complex traits remains unexplained. Rare variants can explain additional disease risk or trait variability. An increasing number of studies are underway to identify trait- and disease-associated rare variants. In this review, we provide an overview of statistical issues in rare-variant association studies with a focus on study designs and statistical tests. We present the design and analysis pipeline of rare-variant studies and review cost-effective sequencing designs and genotyping platforms. We compare various gene- or region-based association tests, including burden tests, variance-component tests, and combined omnibus tests, in terms of their assumptions and performance. Also discussed are the related topics of meta-analysis, population-stratification adjustment, genotype imputation, follow-up studies, and heritability due to rare variants. We provide guidelines for analysis and discuss some of the challenges inherent in these studies and future research directions. PMID:24995866

  18. TNFSF4 polymorphisms are associated with systemic lupus erythematosus in the Malaysian population.

    PubMed

    Chua, K H; Ooh, Y Y; Chai, H C

    2016-10-01

    Tumour necrosis factor superfamily 4 (TNFSF4) gene has been reported to be associated with systemic lupus erythematosus (SLE) susceptibility due to its encoding for OX40L protein that can increase autoantibody production and cause imbalance of T-cell proliferation. The purpose of this study was to investigate the association of TNFSF4 rs2205960, rs1234315, rs8446748 and rs704840 with SLE in the Malaysian population. A total of 476 patients with SLE and 509 healthy controls were recruited. Real-time polymerase chain reaction (PCR) was applied to genotype the selected single nucleotide polymorphisms (SNPs). Allelic and genotypic frequencies of each SNP were calculated for each ethnic group, and association test was performed using logistic regression. The overall association of each SNP in Malaysian patients with SLE was determined with meta-analysis. The frequency of minor T allele of TNFSF4 rs2205960 was significant in Chinese and Indian patients with SLE, with P values of 0.05 (OR = 1.27, 95% CI: 1.00-1.61) and 0.004 (OR = 3.16, 95% CI: 1.41-7.05), respectively. Significant association of minor G allele of rs704840 with SLE was also observed in Chinese (P = 0.03, OR = 1.26, 95% CI: 1.02-1.56). However, after Bonferroni correction, only T allele of rs2205960 remained significantly associated with Indian cohort. Overall, minor G allele of rs704840 showed significant association with SLE in the Malaysian population with P values of 0.05 (OR = 1.20, 95% CI: 1.00-1.43). We suggested TNFSF4 rs704840 could be the potential SLE risk factors in the Malaysian population. © 2016 John Wiley & Sons Ltd.

  19. Microsatellite data analysis for population genetics

    USDA-ARS?s Scientific Manuscript database

    Theories and analytical tools of population genetics have been widely applied for addressing various questions in the fields of ecological genetics, conservation biology, and any context where the role of dispersal or gene flow is important. Underlying much of population genetics is the analysis of ...

  20. Emerging health care-associated infections in the geriatric population.

    PubMed Central

    Strausbaugh, L. J.

    2001-01-01

    The increasing number of persons >65 years of age form a special population at risk for nosocomial and other health care-associated infections. The vulnerability of this age group is related to impaired host defenses such as diminished cell-mediated immunity. Lifestyle considerations, e.g., travel and living arrangements, and residence in nursing homes, can further complicate the clinical picture. The magnitude and diversity of health care-associated infections in the aging population are generating new arenas for prevention and control efforts. PMID:11294721

  1. Sex-specific associations of serum uric acid with metabolic syndrome in Chinese rural population: The RuralDiab study.

    PubMed

    Zhang, Honglei; Li, Yuqian; Mao, Zhenxing; Liu, Xiaotian; Zhang, Xia; Yang, Kaili; Liu, Ruihua; Qian, Xinling; Zhang, Haiqing; Jiang, Jingjing; Zhang, Gongyuan; Wang, Chongjian

    2018-05-01

    We explored the association between serum uric acid (SUA) and metabolic syndrome (MetS) in Chinese rural adults. A total of 16,577 subjects (6354 men and 10,223 women) were from the RuralDiab study. SUA concentration was measured by the enzymatic colorimetric method. A meta-analysis including 12 eligible studies focused on SUA and MetS was preformed to confirm the findings of the cross-sectional study. After adjustment for age, educational level, and other covariates, the odds ratio (ORs) for MetS increased smoothly with the increasing SUA concentration in both sexes (P for no-linear trend > 0.05). The adjusted ORs of MetS comparing the fourth and firstly quartiles were 3.11 [95% CI: 2.58-3.74] in men and 3.64 [95% CI: 3.22-4.11] in women (P trend  < 0.001). In continuous analysis, each 1 mg/dl increment in SUA concentration was significantly associated with a 41% increased risk of MetS in men and 62% in women. The meta-analysis validated the positive association between SUA and MetS (pooled OR: Men, 1.80 [95% CI: 1.57-2.07]; Women, 2.46 [95% CI: 1.95-3.12]). SUA concentration was positively with the prevalence of MetS in Chinese rural population, and more studies are needed to explore the mechanisms of the relationship. WHAT IS ALREADY KNOWN ON THIS TOPIC?: Previous studies have explored the association between serum uric acid and metabolic syndrome, but evidence on the strength and consistency of the association remains uncertain and limited, especially in rural population. In addition, the epidemiological research and meta-analysis on the association have not been reported. WHAT DOES THIS STUDY ADD?: The results of this study showed that serum uric acid was significantly associated with metabolic syndrome and its components in Chinese rural population. Furthermore, the findings demonstrated that the significant associations varied across sex. In addition, the results of epidemiological research were similar with the meta-analysis, which demonstrates

  2. Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis.

    PubMed

    Contractor, Tahmeed; Beri, Abhimanyu; Gardiner, Joseph C; Tang, Xiaoqin; Dwamena, Francesca C

    2015-01-01

    Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

  3. Using population viability analysis, genomics, and habitat suitability to forecast future population patterns of Little Owl Athene noctua across Europe.

    PubMed

    Andersen, Line Holm; Sunde, Peter; Pellegrino, Irene; Loeschcke, Volker; Pertoldi, Cino

    2017-12-01

    The agricultural scene has changed over the past decades, resulting in a declining population trend in many species. It is therefore important to determine the factors that the individual species depend on in order to understand their decline. The landscape changes have also resulted in habitat fragmentation, turning once continuous populations into metapopulations. It is thus increasingly important to estimate both the number of individuals it takes to create a genetically viable population and the population trend. Here, population viability analysis and habitat suitability modeling were used to estimate population viability and future prospects across Europe of the Little Owl Athene noctua , a widespread species associated with agricultural landscapes. The results show a high risk of population declines over the coming 100 years, especially toward the north of Europe, whereas populations toward the southeastern part of Europe have a greater probability of persistence. In order to be considered genetically viable, individual populations must count 1,000-30,000 individuals. As Little Owl populations of several countries count <30,000, and many isolated populations in northern Europe count <1,000 individuals, management actions resulting in exchange of individuals between populations or even countries are probably necessary to prevent losing <1% genetic diversity over a 100-year period. At a continental scale, a habitat suitability analysis suggested Little Owl to be affected positively by increasing temperatures and urban areas, whereas an increased tree cover, an increasing annual rainfall, grassland, and sparsely vegetated areas affect the presence of the owl negatively. However, the low predictive power of the habitat suitability model suggests that habitat suitability might be better explained at a smaller scale.

  4. The CAPN10 Gene Is Associated with Insulin Resistance Phenotypes in the Spanish Population

    PubMed Central

    Sáez, María E.; González-Sánchez, José L.; Ramírez-Lorca, Reposo; Martínez-Larrad, María T.; Zabena, Carina; González, Alejandro; Morón, Francisco J.; Ruiz, Agustín; Serrano-Ríos, Manuel

    2008-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the industrialized world. Familial aggregation of cardiovascular risk factors is a frequent finding, but genetic factors affecting its presentation are still poorly understood. The calpain 10 gene (CAPN10) has been associated with type 2 diabetes (T2DM), a complex metabolic disorder with increased risk of cardiovascular disease. Moreover, the CAPN10 gene has been associated with the presence of metabolic syndrome (MS) in T2DM and in polycystic ovary syndrome (PCOS). In this work, we have analysed whether the polymorphisms UCSNP44, -43, -19 and -63 are related to several cardiovascular risk factors in the context of MS. Molecular analysis of CAPN10 gene was performed in 899 individuals randomly chosen from a cross-sectional population-based epidemiological survey. We have found that CAPN10 gene in our population is mainly associated with two indicators of the presence of insulin resistance: glucose levels two hours after a 75-g oral glucose tolerance test (OGTT) and HOMA values, although cholesterol levels and blood pressure values are also influenced by CAPN10 variants. In addition, the 1221/1121 haplogenotype is under-represented in individuals that fulfil the International Diabetes Federation (IDF) diagnostic criteria for MS. Our results suggest that CAPN10 gene is associated with insulin resistance phenotypes in the Spanish population. PMID:18698425

  5. No association between the protein tyrosine phosphatase, receptor-type, Z Polypeptide 1 (PTPRZ1) gene and schizophrenia in the Japanese population.

    PubMed

    Ito, Yoshihito; Yamada, Shinnosuke; Takahashi, Nagahide; Saito, Shinichi; Yoshimi, Akira; Inada, Toshiya; Noda, Yukihiro; Ozaki, Norio

    2008-10-05

    NRG1-ERBB signaling influences the risk for schizophrenia pathology. A recent study has reported that MAGI1, MAGI2, and protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1; located on 7q31.3) gene products regulate the NRG1-ERBB4 signaling pathway, and PTPRZ1 is associated with schizophrenia in a Caucasian population. By applying a gene-based association concept, we analyzed any association between PTPRZ1 tagging SNPs and schizophrenia in the Japanese population (576 schizophrenics and 768 controls). After linkage disequilibrium analysis, 29 single nucleotide polymorphisms (SNPs) were genotyped using a 5'-exonuclease allelic discrimination assay. We found a significant association of one tagging SNP in a genotype-wise analysis (P = 0.007); however, this might be resulted from type I error due to multiple testing (P = 0.17 after SNPSpD correction). No association was observed between schizophrenic patients and controls in either allelic, genotypic, or haplotypic analyses. Our results therefore suggest that PTPRZ1 is unlikely to be related to the development of schizophrenia in the Japanese population.

  6. Meta-analysis of gene-level tests for rare variant association.

    PubMed

    Liu, Dajiang J; Peloso, Gina M; Zhan, Xiaowei; Holmen, Oddgeir L; Zawistowski, Matthew; Feng, Shuang; Nikpay, Majid; Auer, Paul L; Goel, Anuj; Zhang, He; Peters, Ulrike; Farrall, Martin; Orho-Melander, Marju; Kooperberg, Charles; McPherson, Ruth; Watkins, Hugh; Willer, Cristen J; Hveem, Kristian; Melander, Olle; Kathiresan, Sekar; Abecasis, Gonçalo R

    2014-02-01

    The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays.

  7. 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.

  8. Comparative Analysis of State Fish Consumption Advisories Targeting Sensitive Populations

    PubMed Central

    Scherer, Alison C.; Tsuchiya, Ami; Younglove, Lisa R.; Burbacher, Thomas M.; Faustman, Elaine M.

    2008-01-01

    Objective Fish consumption advisories are issued to warn the public of possible toxicological threats from consuming certain fish species. Although developing fetuses and children are particularly susceptible to toxicants in fish, fish also contain valuable nutrients. Hence, formulating advice for sensitive populations poses challenges. We conducted a comparative analysis of advisory Web sites issued by states to assess health messages that sensitive populations might access. Data sources We evaluated state advisories accessed via the National Listing of Fish Advisories issued by the U.S. Environmental Protection Agency. Data extraction We created criteria to evaluate advisory attributes such as risk and benefit message clarity. Data synthesis All 48 state advisories issued at the time of this analysis targeted children, 90% (43) targeted pregnant women, and 58% (28) targeted women of childbearing age. Only six advisories addressed single contaminants, while the remainder based advice on 2–12 contaminants. Results revealed that advisories associated a dozen contaminants with specific adverse health effects. Beneficial health effects of any kind were specifically associated only with omega-3 fatty acids found in fish. Conclusions These findings highlight the complexity of assessing and communicating information about multiple contaminant exposure from fish consumption. Communication regarding potential health benefits conferred by specific fish nutrients was minimal and focused primarily on omega-3 fatty acids. This overview suggests some lessons learned and highlights a lack of both clarity and consistency in providing the breadth of information that sensitive populations such as pregnant women need to make public health decisions about fish consumption during pregnancy. PMID:19079708

  9. Linkage disequilibrium and association analysis of stripe rust resistance in wild emmer wheat (Triticum turgidum ssp. dicoccoides) population in Israel.

    PubMed

    Sela, Hanan; Ezrati, Smadar; Ben-Yehuda, Pnina; Manisterski, Jacob; Akhunov, Eduard; Dvorak, Jan; Breiman, Adina; Korol, Abraham

    2014-11-01

    Rapid LD decay in wild emmer population from Israel allows high-resolution association mapping. Known and putative new stripe rust resistance genes were found. Genome-wide association mapping (GWAM) is becoming an important tool for the discovery and mapping of loci underlying trait variation in crops, but in the wild relatives of crops the use of GWAM has been limited. Critical factors for the use of GWAM are the levels of linkage disequilibrium (LD) and genetic diversity in mapped populations, particularly in those of self-pollinating species. Here, we report LD estimation in a population of 128 accessions of self-pollinating wild emmer, Triticum turgidum ssp. dicoccoides, the progenitor of cultivated wheat, collected in Israel. LD decayed fast along wild emmer chromosomes and reached the background level within 1 cM. We employed GWAM for the discovery and mapping of genes for resistance to three isolates of Puccinia striiformis, the causative agent of wheat stripe rust. The wild emmer population was genotyped with the wheat iSelect assay including 8643 gene-associated SNP markers (wheat 9K Infinium) of which 2,278 were polymorphic. The significance of association between stripe rust resistance and each of the polymorphic SNP was tested using mixed linear model implemented in EMMA software. The model produced satisfactory results and uncovered four significant associations on chromosome arms 1BS, 1BL and 3AL. The locus on 1BS was located in a region known to contain stripe rust resistance genes. These results show that GWAM is an effective strategy for gene discovery and mapping in wild emmer that will accelerate the utilization of this genetic resource in wheat breeding.

  10. Population genetic analysis of Enterocytozoon bieneusi in humans.

    PubMed

    Li, Wei; Cama, Vitaliano; Feng, Yaoyu; Gilman, Robert H; Bern, Caryn; Zhang, Xichen; Xiao, Lihua

    2012-01-01

    Genotyping based on sequence analysis of the ribosomal internal transcribed spacer has revealed significant genetic diversity in Enterocytozoonbieneusi. Thus far, the population genetics of E. bieneusi and its significance in the epidemiology of microsporidiosis have not been examined. In this study, a multilocus sequence typing of E. bieneusi in AIDS patients in Lima, Peru was conducted, using 72 specimens previously genotyped as A, D, IV, EbpC, WL11, Peru7, Peru8, Peru10 and Peru11 at the internal transcribed spacer locus. Altogether, 39 multilocus genotypes were identified among the 72 specimens. The observation of strong intragenic linkage disequilibria and limited genetic recombination among markers were indicative of an overall clonal population structure of E. bieneusi. Measures of pair-wise intergenic linkage disequilibria and a standardised index of association (IAS) based on allelic profile data further supported this conclusion. Both sequence-based and allelic profile-based phylogenetic analyses showed the presence of two genetically isolated groups in the study population, one (group 1) containing isolates of the anthroponotic internal transcribed spacer genotype A, and the other (group 2) containing isolates of multiple internal transcribed spacer genotypes (mainly genotypes D and IV) with zoonotic potential. The measurement of linkage disequilibria and recombination indicated group 2 had a clonal population structure, whereas group 1 had an epidemic population structure. The formation of the two sub-populations was confirmed by STRUCTURE and Wright's fixation index (FST) analyses. The data highlight the power of MLST in understanding the epidemiology of E. bieneusi. Published by Elsevier Ltd.

  11. Comparison of refractive errors and factors associated with spectacle use in a rural and urban South Indian population.

    PubMed

    Prema, Raju; George, Ronnie; Sathyamangalam Ve, Ramesh; Hemamalini, Arvind; Baskaran, Mani; Kumaramanickavel, Govindaswamy; Catherine, McCarty; Vijaya, Lingam

    2008-01-01

    To compare the prevalence of refractive errors and factors associated with spectacle use in a rural and urban south Indian population. Four thousand eight hundred subjects (age> 39 years) each from rural and urban Tamil Nadu were enumerated for a population-based study. All participants underwent a complete ophthalmic evaluation including best-corrected visual acuity (BCVA), objective and subjective refraction. Out of 3924 rural responders 63.91% and out of 3850 urban responders 81.64% were phakic in the right eye with BCVA of 20/40 or better and were included in the study. Association of spectacle use and refractive errors with different parameters were analysed using logistic regression. Chi square, t test, Chi square for trend and Pearson's correlation coefficient were used for analysis. Spectacle use was significantly higher and positively associated with literacy and employment in the urban population. The age and gender-adjusted prevalence of emmetropia, myopia of spherical equivalent (SE) < or =-0.50 diopter sphere (DS), high myopia (SE < or =-5.00DS), hyperopia (SE> 0.50DS) and astigmatism < or = 0.50 diopter cylinder (DC) were 46.8%, 31.0%, 4.3%, 17.9% and 60.4% respectively in the rural population and 29.0%, 17.6%, 1.5%, 51.9%, 59.1% respectively in the urban population. The prevalence of emmetropia decreased with age ( p p = 0.001) and were associated with nuclear sclerosis ( p = 0.001) in both populations. Hyperopia was commoner among women than men ( p = 0.001); was positively associated with diabetes mellitus ( p = 0.008) in the rural population and negatively with nuclear sclerosis ( p = 0.001) in both populations. Spectacle use was found to be significantly lower in the rural population. The pattern of refractive errors was significantly different between both populations.

  12. Age-specific associations between cardiac vagal activity and functional somatic symptoms: a population-based study.

    PubMed

    Tak, Lineke M; Janssens, Karin A M; Dietrich, Andrea; Slaets, Joris P J; Rosmalen, Judith G M

    2010-01-01

    Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is cross-sectionally and prospectively associated with the number of FSS in the general population. This study was performed in a population-based cohort of 774 adults (45.1% male, mean age +/- SD 53.5 +/- 10.7 years). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF), reflecting cardiac vagal activity. Follow-up measurements of HRV-HF and FSS were performed approximately 2 years later. Linear regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, revealed an interaction of cardiac vagal activity with age: HRV-HF was negatively associated with FSS in adults 52 years (beta = 0.13, t = 2.51, p = 0.012). Longitudinal analysis demonstrated a similar pattern. Decreased cardiac vagal activity is associated with a higher number of FSS in adults aged population. The unexpected association between increased cardiac vagal activity and FSS in adults aged >52 years needs further exploration. The role of age should be acknowledged in future studies on ANS function in the etiology of FSS. (c) 2010 S. Karger AG, Basel.

  13. [A Meta-analysis on tea drinking and the risk of lung cancer in Chinese population].

    PubMed

    Jin, Zi-yi; Han, Ren-qiang; Liu, Ai-min; Wang, Xu-shan; Wu, Ming; Zhang, Zuo-feng; Zhao, Jin-kou

    2012-08-01

    To examine the association between tea drinking and the risk of lung cancer in Chinese population. All relevant published articles in Chinese and English literature database were identified. Meta-analysis was conducted. Combined odds ratio (OR) and 95% confidence interval (CI) were calculated to estimate the associations and dose-response relationship between tea drinking and the risk of lung cancer. Twelve studies were included. An inverse association with lung cancer was observed on tea drinkers when compared to non-tea drinkers (OR = 0.66, 95%CI: 0.49 - 0.89). Tea drinking might serve as a protective factor on lung cancer in the Chinese population.

  14. Fast Genome-Wide QTL Association Mapping on Pedigree and Population Data.

    PubMed

    Zhou, Hua; Blangero, John; Dyer, Thomas D; Chan, Kei-Hang K; Lange, Kenneth; Sobel, Eric M

    2017-04-01

    Since most analysis software for genome-wide association studies (GWAS) currently exploit only unrelated individuals, there is a need for efficient applications that can handle general pedigree data or mixtures of both population and pedigree data. Even datasets thought to consist of only unrelated individuals may include cryptic relationships that can lead to false positives if not discovered and controlled for. In addition, family designs possess compelling advantages. They are better equipped to detect rare variants, control for population stratification, and facilitate the study of parent-of-origin effects. Pedigrees selected for extreme trait values often segregate a single gene with strong effect. Finally, many pedigrees are available as an important legacy from the era of linkage analysis. Unfortunately, pedigree likelihoods are notoriously hard to compute. In this paper, we reexamine the computational bottlenecks and implement ultra-fast pedigree-based GWAS analysis. Kinship coefficients can either be based on explicitly provided pedigrees or automatically estimated from dense markers. Our strategy (a) works for random sample data, pedigree data, or a mix of both; (b) entails no loss of power; (c) allows for any number of covariate adjustments, including correction for population stratification; (d) allows for testing SNPs under additive, dominant, and recessive models; and (e) accommodates both univariate and multivariate quantitative traits. On a typical personal computer (six CPU cores at 2.67 GHz), analyzing a univariate HDL (high-density lipoprotein) trait from the San Antonio Family Heart Study (935,392 SNPs on 1,388 individuals in 124 pedigrees) takes less than 2 min and 1.5 GB of memory. Complete multivariate QTL analysis of the three time-points of the longitudinal HDL multivariate trait takes less than 5 min and 1.5 GB of memory. The algorithm is implemented as the Ped-GWAS Analysis (Option 29) in the Mendel statistical genetics package, which is

  15. Measles outbreaks in displaced populations: a review of transmission, morbidity and mortality associated factors.

    PubMed

    Kouadio, Isidore K; Kamigaki, Taro; Oshitani, Hitoshi

    2010-03-19

    Measles is a highly contagious infectious disease with a significant public health impact especially among displaced populations due to their characteristic mass population displacement, high population density in camps and low measles vaccination coverage among children. While the fatality rate in stable populations is generally around 2%, evidence shows that it is usually high among populations displaced by disasters. In recent years, refugees and internally displaced persons have been increasing. Our study aims to define the epidemiological characteristics and risk factors associated with measles outbreaks in displaced populations. We reviewed literature in the PubMed database, and selected articles for our analysis that quantitatively described measles outbreaks. A total of nine articles describing 11 measles outbreak studies were selected. The outbreaks occurred between 1979 and 2005 in Asia and Africa, mostly during post-conflict situations. Seven of eight outbreaks were associated with poor vaccination status (vaccination coverage; 17-57%), while one was predominantly due to one-dose vaccine coverage. The age of cases ranged from 1 month to 39 years. Children aged 6 months to 5 years were the most common target group for vaccination; however, 1622 cases (51.0% of the total cases) were older than 5 years of age. Higher case-fatality rates (>5%) were reported for five outbreaks. Consistent factors associated with measles transmission, morbidity and mortality were vaccination status, living conditions, movements of refugees, nutritional status and effectiveness of control measures including vaccination campaigns, surveillance and security situations in affected zones. No fatalities were reported in two outbreaks during which a combination of active and passive surveillance was employed. Measles patterns have varied over time among populations displaced by natural and man-made disasters. Appropriate risk assessment and surveillance strategies are essential

  16. "A Body Shape Index" in middle-age and older Indonesian population: scaling exponents and association with incident hypertension.

    PubMed

    Cheung, Yin Bun

    2014-01-01

    "A Body Shape Index" (ABSI) is a recently proposed index that standardizes waist circumference for body mass index (BMI) and height. This study aims to: (a) examine if the ABSI scaling exponents for standardizing waist circumference for BMI and height are valid in middle-aged and older Indonesian population, and (b) compare the association between incident hypertension and ABSI and other anthropometric measures. The Indonesian Family Life Survey Wave 3 measured anthropometric variables and blood pressure of 8255 adults aged between 40 to 85 years in 2000. The relationship between two anthropometric quantities, e.g. weight (w) and height (h), can be expressed as the power law-equivalent [Formula: see text], where p = 2 is the scaling exponent in the derivation of the BMI and can be estimated by linear regression analysis. This was extended to the regression analysis of the log-transformed waist circumference, weight and height to establish the scaling exponents in the ABSI. The values for men were similar to those developed by the previous American study, which were 2/3 (BMI) and 1/2 (height). Those for women were somewhat smaller, at 3/5 (BMI) and 1/5 (height). The original (American) ABSI leads to mild negative correlation with BMI (-0.14) and height (-0.12) in the female population. Analysis of the development of hypertension between Waves 3 and 4 (average interval 7.5 years) in relation to ABSI measured at Wave 3 showed stronger association if the locally derived (Indonesian) scaling exponents were used. However, both versions of the ABSI were less associated with incident hypertension than waist circumference and BMI. The values for the scaling exponents for ABSI are roughly similar between the American population and the middle-aged and older Indonesian population, although larger discrepancy was found in women. The ABSI is less associated with incident hypertension than waist circumference and BMI.

  17. Population stratification effect on cancer susceptibility in an admixed population from Brazilian Amazon.

    PubMed

    Vieira, Priscilla Cristina Moura; Burbano, Rommel Mario Rodríguez; Fernandes, Débora Christina Ricardo Oliveira; Montenegro, Raquel Carvalho; Dos Santos, Sidney Emanuel Batista; Sortica, Vinicius Albuquerque; Assumpção, Paulo Pimentel; Ribeiro-Dos-Santos, Ândrea Kely Campos; Carvalho, Antônio Alberto; Dos Santos, Ney Pereira Carneiro

    2015-04-01

    Many efforts have been made to identify candidate genes involved in cancer susceptibility. The present study aimed to investigate the association between Arg194Trp (XRCC1), Ala222Val (MTHFR) and Arg521Lys (EGFR) polymorphisms (SNPs) and their susceptibility to gastric and breast carcinoma cancer in patients from Brazilian Amazon, controlling population structure interference. The SNPs were genotyped by TaqMan® SNP Genotyping Assays. Ancestry was estimated by analysis of a panel with 48 ancestry informative markers. Logistic regression analysis showed an inverse association with a 10% increase in African and European ancestry and cancer risk (odds ratio (OR)=1.919 and 0.676, respectively). In a preliminary Chi-square analysis a positive association between Arg521Lys (EGFR) polymorphism and carcinoma susceptibility was found (p=0.037); however, when two different methodologies to control population structure bias were utilized, this association was lost (p=0.064 and p=0.256). Genetic ancestry influence gastric and breast cancer risk and highlight the importance of population structure inference in association studies in highly admixed populations, such as those from Brazilian Amazon. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Serotonin transporter promoter variants: Analysis in Indian autistic and control population.

    PubMed

    Guhathakurta, Subhrangshu; Ghosh, Sagarmoy; Sinha, Swagata; Chatterjee, Anindita; Ahmed, Shabina; Chowdhury, Susanta Roy; Gangopadhyay, Prasanta Kumar; Ghosh, Saurabh; Singh, Manoranjan; Usha, Rajamma

    2006-05-30

    Serotonin transporter (5-HTT) is a transmembrane protein belonging to Na+/Cl- dependent membrane transporter family and transports 5-HT across the membranes of presynaptic neurons. 5-HTT-linked polymorphic region (5-HTTLPR) gained much interest because of the differential regulation of expression and activity of 5-HTT by its various genotypes. A population-based study has been conducted on 5-HTTLPR with 358 individuals, which included 79 autistic probands, 136 parents, and 143 controls from two subpopulations of east and northeast regions of India. The genotypic frequencies of all the groups conform to Hardy-Weinberg equilibrium. With the finding of efficacy of serotonin reuptake inhibitors in ameliorating ritualistic behavior in autistic disorder, 5-HTT emerged as a putative candidate gene for autism and association studies have been carried out in different ethnic populations. But these studies were inconclusive due to conflicting results on association. Because such a study has never been performed in the Indian population, we have tested the possible involvement of 5-HTTLPR polymorphism with autism. The present study failed to establish any association or linkage of 5-HTTLPR with autism in the Indian population by case-control studies (chi2 = 1.314, P = 0.63) and family-based approaches (TDT chi2 = 0.22, P = 0.64 and HHRR-chi2 = 0.25, P = 0.61). However, when a meta-analysis of all the available TDT data, inclusive of the present study is carried out, we observed a significant preferential transmission of S-allele from parents to the affected offspring (chi2 = 7.51, P = 0.006) indicating an association of 5-HTTLPR with autism.

  19. Association of Climatic Variability, Vector Population and Malarial Disease in District of Visakhapatnam, India: A Modeling and Prediction Analysis.

    PubMed

    Srimath-Tirumula-Peddinti, Ravi Chandra Pavan Kumar; Neelapu, Nageswara Rao Reddy; Sidagam, Naresh

    2015-01-01

    Malarial incidence, severity, dynamics and distribution of malaria are strongly determined by climatic factors, i.e., temperature, precipitation, and relative humidity. The objectives of the current study were to analyse and model the relationships among climate, vector and malaria disease in district of Visakhapatnam, India to understand malaria transmission mechanism (MTM). Epidemiological, vector and climate data were analysed for the years 2005 to 2011 in Visakhapatnam to understand the magnitude, trends and seasonal patterns of the malarial disease. Statistical software MINITAB ver. 14 was used for performing correlation, linear and multiple regression analysis. Perennial malaria disease incidence and mosquito population was observed in the district of Visakhapatnam with peaks in seasons. All the climatic variables have a significant influence on disease incidence as well as on mosquito populations. Correlation coefficient analysis, seasonal index and seasonal analysis demonstrated significant relationships among climatic factors, mosquito population and malaria disease incidence in the district of Visakhapatnam, India. Multiple regression and ARIMA (I) models are best suited models for modeling and prediction of disease incidences and mosquito population. Predicted values of average temperature, mosquito population and malarial cases increased along with the year. Developed MTM algorithm observed a major MTM cycle following the June to August rains and occurring between June to September and minor MTM cycles following March to April rains and occurring between March to April in the district of Visakhapatnam. Fluctuations in climatic factors favored an increase in mosquito populations and thereby increasing the number of malarial cases. Rainfall, temperatures (20°C to 33°C) and humidity (66% to 81%) maintained a warmer, wetter climate for mosquito growth, parasite development and malaria transmission. Changes in climatic factors influence malaria directly by

  20. Association of Climatic Variability, Vector Population and Malarial Disease in District of Visakhapatnam, India: A Modeling and Prediction Analysis

    PubMed Central

    Srimath-Tirumula-Peddinti, Ravi Chandra Pavan Kumar; Neelapu, Nageswara Rao Reddy; Sidagam, Naresh

    2015-01-01

    Background Malarial incidence, severity, dynamics and distribution of malaria are strongly determined by climatic factors, i.e., temperature, precipitation, and relative humidity. The objectives of the current study were to analyse and model the relationships among climate, vector and malaria disease in district of Visakhapatnam, India to understand malaria transmission mechanism (MTM). Methodology Epidemiological, vector and climate data were analysed for the years 2005 to 2011 in Visakhapatnam to understand the magnitude, trends and seasonal patterns of the malarial disease. Statistical software MINITAB ver. 14 was used for performing correlation, linear and multiple regression analysis. Results/Findings Perennial malaria disease incidence and mosquito population was observed in the district of Visakhapatnam with peaks in seasons. All the climatic variables have a significant influence on disease incidence as well as on mosquito populations. Correlation coefficient analysis, seasonal index and seasonal analysis demonstrated significant relationships among climatic factors, mosquito population and malaria disease incidence in the district of Visakhapatnam, India. Multiple regression and ARIMA (I) models are best suited models for modeling and prediction of disease incidences and mosquito population. Predicted values of average temperature, mosquito population and malarial cases increased along with the year. Developed MTM algorithm observed a major MTM cycle following the June to August rains and occurring between June to September and minor MTM cycles following March to April rains and occurring between March to April in the district of Visakhapatnam. Fluctuations in climatic factors favored an increase in mosquito populations and thereby increasing the number of malarial cases. Rainfall, temperatures (20°C to 33°C) and humidity (66% to 81%) maintained a warmer, wetter climate for mosquito growth, parasite development and malaria transmission. Conclusions

  1. Association between emergency admission for peptic ulcer bleeding and air pollution: a case-crossover analysis in Hong Kong's elderly population.

    PubMed

    Tian, Linwei; Qiu, Hong; Sun, Shengzhi; Tsang, Hilda; Chan, King-Pan; Leung, Wai K

    2017-05-01

    Air pollution increases intestinal permeability, alters the gut microbiome, and promotes inflammation, which might contribute towards gastrointestinal bleeding. In the present study, we aim to examine whether short-term elevations in air pollution are associated with increased numbers of emergency hospital admissions for peptic ulcer bleeding in Hong Kong. Daily air pollution (particulate matter with aerodynamic diameter less than 2·5 μm [PM 2·5 ], nitric oxide [NO 2 ], sulpher dioxide [SO 2 ], and ozone [O 3 ]) data during 2005-10 were collected from the Environmental Protection Department and emergency admission data for peptic ulcer bleeding in elderly people (aged 65 years or older) from the Hospital Authority of Hong Kong. A time stratified case-crossover analysis with conditional logistic regression was used to estimate the excess risk of peptic ulcer bleeding associated with each air pollutant, in single-pollutant and multi-pollutant models. Cardiorespiratory diseases were used as positive controls. 8566 emergency admissions for peptic ulcer bleeding were recorded among Hong Kong's elderly population during 2005-10; the daily number of admissions ranged from 0 to 13. An IQR increment of 5-day moving average (lag 04 ) of NO 2 concentration (25·8 μg/m 3 ) was associated with a 7·6% (95% CI 2·2-13·2) increase in emergency admissions for peptic ulcer bleeding. Multi-pollutant models confirmed the robustness of the risk estimates for NO 2 . Other pollutants (PM 2·5 , SO 2 , and O 3 ) were not associated with peptic ulcer bleeding admissions. Short-term elevation in ambient NO 2 might trigger peptic ulcer bleeding events and increase the risk of emergency admissions for peptic ulcer bleeding in Hong Kong's elderly population. These findings strengthen the hypothesis that air pollution affects not just cardiopulmonary diseases, but also certain diseases of the digestive system. None. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an

  2. Genetic association study of Age-Related Macular Degeneration in the Spanish population

    PubMed Central

    Brión, María; Sanchez-Salorio, Manuel; Cortón, Marta; de la Fuente, Maria; Pazos, Belen; Othman, Mohammad; Swaroop, Anand; Abecasis, Goncalo; Sobrino, Beatriz; Carracedo, Angel

    2017-01-01

    Purpose To investigate new genetic risk factors and replicate reported associations with advanced age related macular degeneration (AMD) in a prospective case - control study developed with a Spanish cohort. Methods Three hundred and fifty-three unrelated patients with advanced AMD (225 with atrophic AMD, 57 with neovascular AMD, and 71 with mixed AMD) and 282 age-matched controls were included. Functional and tagging SNPs in 55 candidate genes were genotyped using the SNPlex™ genotyping system. Single SNP and haplotype association analysis were performed to determine possible genetic associations; interaction effects between SNPs were also investigated. Results In agreement with previous reports, ARMS2 and CFH genes were strongly associated with AMD in the studied Spanish population. Moreover, both loci influenced risk independently giving support to different pathways implicated in AMD pathogenesis. No evidence for association of advanced AMD with other previous reported susceptibility genes, such as CST3, CX3CR1, FBLN5, HMCN1, PON1, SOD2, TLR4, VEGF and VLDLR, was detected. However, two additional genes appear to be candidate markers for the development of advanced AMD. A variant located at the 3´UTR of the FGF2 gene (rs6820411) was highly associated with atrophic AMD, and the functional SNP rs3112831 at ABCA4 showed a marginal association with the disease. Conclusion We performed a large gene association study in advanced AMD in a Spanish population. Our findings show that CFH and ARMS2 genes seem to be the principal risk loci contributing independently to AMD in our cohort. We report new significant associations that could also influence the development of advanced AMD. These findings should be confirmed in further studies with larger cohorts. PMID:21106043

  3. The Dynamics of Population, Built-up Areas and their Evolving Associations in Gridded Population across Time and Space

    NASA Astrophysics Data System (ADS)

    Stevens, F. R.; Gaughan, A. E.; Tatem, A. J.; Linard, C.; Sorichetta, A.; Nieves, J. J.; Reed, P.

    2017-12-01

    Gridded population data is commonly used to understand the `now' of hazard risk and mitigation management, health and disease modelling, and global change-, economic-, environmental-, and sustainability-related research. But to understand how human population change at local to global scales influences and is influenced by environmental changes requires novel ways of treating data and statistically describing associations of measured population counts with associated covariates. One of the most critical components in such gridded estimates is the relationship between built-up areas and population located in these areas. This relationship is rarely static and accurately estimating changes in built-areas through time and the changing human population around them is critical when applying gridded population datasets in studies of other environmental change. The research presented here discusses these issues in the context of multitemporal, gridded population data, using new technologies and sources of remotely-sensed and modeled built-up areas. We discuss applications of these data in environmental analyses and intercomparisons with other such data across scales.

  4. Type D personality is associated with social anxiety in the general population.

    PubMed

    Kupper, Nina; Denollet, Johan

    2014-06-01

    Research on the emotional processes associated with Type D personality is important for its further conceptualization. We examined the associations of Type D personality with social and general anxiety symptoms in a large community sample. The aim of the current study was to disentangle the associations of Type D personality and its components with social anxiety and general anxiety in a large sample from the general population. A random sample of 2,475 adults from the general population filled out questionnaires to assess Type D personality (DS-14), social anxiety (SIAS(10), SPS(11), BFNE-II), and general anxiety (HADS-A, GAD-7). Type D individuals were characterized by increased levels of both social and general anxiety. The social inhibition (SI) component of Type D personality was most strongly associated with social interaction anxiety (r = .63), while negative affectivity (NA) was strongly associated with general anxiety (GAD-7: r = .70; HADS-A: r = .66). Within social anxiety, SI was more strongly associated with facets of social interaction anxiety than with social phobia. Multiple regression analysis showed that the synergistic interaction of NA and SI was a predictor of social anxiety (SIAS(10): β = .32, p < .0005; SPS(11): β = .27, p < .0005; BFNE-II: β = .11, p = .007) independent of demographics and the scores on the individual Type D components. This interaction was not a significant predictor of general anxiety. Logistic regression using the dichotomous Type D classification demonstrated a 9.1-fold (95%CI, 7.0-11.8) increased odds of a score in the highest quartile of social interaction anxiety and a 7.6-fold (95%CI, 5.8-9.8) increased odds of high social phobia. Odds ratios for clinically relevant levels of general anxiety were 8.3 (95%CI, 5.5-12.5) for GAD-7 and 6.5 (95%CI, 3.4-12.6) for HADS-A. In the general population, Type D individuals were characterized by both social and general anxiety. The SI component of Type D is strongly associated

  5. Association between serum osteocalcin level and blood pressure in a Chinese population.

    PubMed

    Xu, Yiting; Ma, Xiaojing; Xiong, Qin; Hu, Xiang; Zhang, Xueli; Yuan, Yeqing; Bao, Yuqian

    2018-04-01

    This observational study investigated the association between serum osteocalcin level and blood pressure in a Chinese population. A total of 2241 subjects (909 men and 1,332 women; age, 24-78 years) from Shanghai communities were recruited. Subjects were divided into non-hypertensive and hypertensive groups according to diagnosis of hypertension based on the 1999 World Health Organization-International Society of Hypertension Guidelines. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. Men in the hypertensive group showed lower serum osteocalcin level compared with those in the non-hypertensive group, [16.37 (13.34-20.11) ng/mL versus 17.01 (14.23-20.79) ng/mL, p = .039]. No difference in serum osteocalcin level was found between the two groups of women (p = .675). An inverse association was observed between serum osteocalcin level and systolic blood pressure (SBP) in men (p = .004), but serum osteocalcin level was not associated with diastolic blood pressure (DBP) in men (p = .472). No associations were detected between serum osteocalcin level and SBP or DBP in women (SBP: p = .108; DBP: p = .575). A multiple stepwise regression analysis showed an inverse association between serum osteocalcin level and SBP in men after adjusting for age, smoking status, family history of hypertension, and lipid and C-reactive protein levels (standardized β = -0.074, p = .023), but the association disappeared after adjustment for body mass index, waist circumference, blood glucose, and homeostasis model assessment of insulin resistance (p = .327). Serum osteocalcin level was not independently associated with blood pressure in a Chinese population.

  6. Soil Bacterial Diversity Is Associated with Human Population Density in Urban Greenspaces.

    PubMed

    Wang, Haitao; Cheng, Minying; Dsouza, Melissa; Weisenhorn, Pamela; Zheng, Tianling; Gilbert, Jack A

    2018-05-01

    Urban greenspaces provide extensive ecosystem services, including pollutant remediation, water management, carbon maintenance, and nutrient cycling. However, while the urban soil microbiota underpin these services, we still have limited understanding of the factors that influence their distribution. We characterized soil bacterial communities from turf-grasses associated with urban parks, streets, and residential sites across a major urban environment, including a gradient of human population density. Bacterial diversity was significantly positively correlated with the population density; and species diversity was greater in park and street soils, compared to residential soils. Population density and greenspace type also led to significant differences in the microbial community composition that was also significantly correlated with soil pH, moisture, and texture. Co-occurrence network analysis revealed that microbial guilds in urban soils were well correlated. Abundant soil microbes in high density population areas had fewer interactions, while abundant bacteria in high moisture soils had more interactions. These results indicate the significant influence of changes in urban demographics and land-use on soil microbial communities. As urbanization is rapidly growing across the planet, it is important to improve our understanding of the consequences of urban zoning on the soil microbiota.

  7. Composition of Bacterial Communities Associated with Aurelia aurita Changes with Compartment, Life Stage, and Population

    PubMed Central

    Weiland-Bräuer, Nancy; Neulinger, Sven C.; Pinnow, Nicole; Künzel, Sven; Baines, John F.

    2015-01-01

    The scyphozoan Aurelia aurita is recognized as a key player in marine ecosystems and a driver of ecosystem change. It is thus intensely studied to address ecological questions, although its associations with microorganisms remain so far undescribed. In the present study, the microbiota associated with A. aurita was visualized with fluorescence in situ hybridization (FISH) analysis, and community structure was analyzed with respect to different life stages, compartments, and populations of A. aurita by 16S rRNA gene amplicon sequencing. We demonstrate that the composition of the A. aurita microbiota is generally highly distinct from the composition of communities present in ambient water. Comparison of microbial communities from different developmental stages reveals evidence for life stage-specific community patterns. Significant restructuring of the microbiota during strobilation from benthic polyp to planktonic life stages is present, arguing for a restructuring during the course of metamorphosis. Furthermore, the microbiota present in different compartments of the adult medusa (exumbrella mucus and gastric cavity) display significant differences, indicating body part-specific colonization. A novel Mycoplasma strain was identified in both compartment-specific microbiota and is most likely present inside the epithelium as indicated by FISH analysis of polyps, indicating potential endosymbiosis. Finally, comparison of polyps of different populations kept under the same controlled laboratory conditions in the same ambient water showed population-specific community patterns, most likely due the genetic background of the host. In conclusion, the presented data indicate that the associated microbiota of A. aurita may play important functional roles, e.g., during the life cycle. PMID:26116680

  8. Variants in the SMARCA4 gene was associated with coronary heart disease susceptibility in Chinese han population.

    PubMed

    Guo, Xuan; Wang, Xiaohong; Wang, Yuan; Zhang, Chunyan; Quan, Xiaohui; Zhang, Yan; Jia, Shan; Ma, Weidong; Fan, Yajie; Wang, Congxia

    2017-01-31

    Coronary heart disease (CHD) is the leading cause of death worldwide. Many single-nucleotide polymorphisms (SNPs) are found to be related to the risk of CHD in previous studies. This study investigated whether polymorphism of SMARCA4 gene is associated with CHD. Genotypes at five CHD-relevant SNPs were determined in 456 cases of incident CHD and 685 unaffected controls in Chinese Han population using χ2 test, genetic model analysis and haplotype analysis. We also analysis the differences in continuous variables among the subjects with three genotypes of related genes were assessed using the ANOVA. We identified two susceptibility SNPs in the SMARCA4 gene that were potentially associated with a decreased risk of CHD. We identified rs11879293 (OR, 0.74; 95% CI, 0.59-0.96; P = 0.012) and rs12232780 (OR, 0.70; 95% CI, 0.54-0.90; P = 0.005) were associated with a decreased risk of CHD risk under the log-additive model adjusted by gender and age. Meanwhile, we also found that significant differences in glucose concentrations with rs11879293 and rs1122608 different genotype. Serum LDL-C and HDL-C were seen among the 3 genotypes of rs12232780 exist differences. This study provides an evidence for polymorphism of SMARCA4 gene associated with CHD development in Chinese Han population.

  9. Association between Serum Testosterone and PSA Levels in Middle-Aged Healthy Men from the General Population.

    PubMed

    Elzanaty, Saad; Rezanezhad, Babak; Dohle, Gert

    2017-04-01

    The aim of the present study was to evaluate the association between serum testosterone and PSA levels in middle-aged healthy men from the general population. Based on 119 healthy men from the general population, total testosterone and PSA levels were measured. Demographic data regarding BMI, waist-to-hip ratio, smoking, and alcohol consumption were also collected. Men were classified into two groups according to testosterone levels; hypogonadal (testosterone ≤ 12 nmol/l), and eugonadal (testosterone > 12 nmol/l). The mean age of the subjects was 55 years (range 46-60 years). No significant correlation between serum testosterone and PSA levels was found (p = 0.60). PSA levels were similar when compared between hypogonadal and eugonadal men (1.4 µg/l vs. 1.4 µg/l, p = 0.90). When using a multivariate analysis model adjusted for the age of the subjects, BMI, waist-to-hip ratio, smoking, and alcohol consumption, a positive significant association between testosterone and PSA levels was found (β = 0.03, 95 % CI = 0.003-0.062, p = 0.03). Only after adjusted multivariate analysis, our results indicated that testosterone was associated with PSA levels in middle-aged healthy men.

  10. Genome-wide association mapping of quantitative traits in a breeding population of sugarcane.

    PubMed

    Racedo, Josefina; Gutiérrez, Lucía; Perera, María Francisca; Ostengo, Santiago; Pardo, Esteban Mariano; Cuenya, María Inés; Welin, Bjorn; Castagnaro, Atilio Pedro

    2016-06-24

    Molecular markers associated with relevant agronomic traits could significantly reduce the time and cost involved in developing new sugarcane varieties. Previous sugarcane genome-wide association analyses (GWAS) have found few molecular markers associated with relevant traits at plant-cane stage. The aim of this study was to establish an appropriate GWAS to find molecular markers associated with yield related traits consistent across harvesting seasons in a breeding population. Sugarcane clones were genotyped with DArT (Diversity Array Technology) and TRAP (Target Region Amplified Polymorphism) markers, and evaluated for cane yield (CY) and sugar content (SC) at two locations during three successive crop cycles. GWAS mapping was applied within a novel mixed-model framework accounting for population structure with Principal Component Analysis scores as random component. A total of 43 markers significantly associated with CY in plant-cane, 42 in first ratoon, and 41 in second ratoon were detected. Out of these markers, 20 were associated with CY in 2 years. Additionally, 38 significant associations for SC were detected in plant-cane, 34 in first ratoon, and 47 in second ratoon. For SC, one marker-trait association was found significant for the 3 years of the study, while twelve markers presented association for 2 years. In the multi-QTL model several markers with large allelic substitution effect were found. Sequences of four DArT markers showed high similitude and e-value with coding sequences of Sorghum bicolor, confirming the high gene microlinearity between sorghum and sugarcane. In contrast with other sugarcane GWAS studies reported earlier, the novel methodology to analyze multi-QTLs through successive crop cycles used in the present study allowed us to find several markers associated with relevant traits. Combining existing phenotypic trial data and genotypic DArT and TRAP marker characterizations within a GWAS approach including population structure as

  11. Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

    PubMed

    Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

    2018-01-01

    An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

  12. The rs7517847 polymorphism in the IL-23R gene is associated with gout in a Chinese Han male population.

    PubMed

    Liu, Shiguo; He, Hongmei; Yu, Renchao; Han, Lin; Wang, Can; Cui, Ying; Li, Changgui

    2015-05-01

    Gout is a polygenic auto-inflammatory disease, in which inflammation plays an important role in disease pathogenesis. The cytokine interleukin (IL)-23 promotes inflammation and helps to guide inflammatory cells, while studies have shown that the IL-23R gene is associated with susceptibility to several immune-related diseases. This study aimed to determine whether the IL-23R rs7517847 (G/T) polymorphism is associated with gout in a Chinese Han male population. We recruited 400 patients with gout and 582 gout-free controls. After obtaining blood samples for DNA extraction, genotyping of the rs7517847 polymorphism was performed by fluorescence-based quantitative PCR using TaqMan probes. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Both genotypic and allelic frequencies of rs7517847 differed significantly between gout patients and controls (χ(2) = 6.792, df = 2, P = 0.034 by genotype; χ(2) = 4.202, df = 1, P = 0.04 by allele). IL-23R may be associated with gout in a Chinese Han male population, although our findings should be confirmed using larger sample sizes and other independent populations.

  13. Demographics of reintroduced populations: estimation, modeling, and decision analysis

    USGS Publications Warehouse

    Converse, Sarah J.; Moore, Clinton T.; Armstrong, Doug P.

    2013-01-01

    Reintroduction can be necessary for recovering populations of threatened species. However, the success of reintroduction efforts has been poorer than many biologists and managers would hope. To increase the benefits gained from reintroduction, management decision making should be couched within formal decision-analytic frameworks. Decision analysis is a structured process for informing decision making that recognizes that all decisions have a set of components—objectives, alternative management actions, predictive models, and optimization methods—that can be decomposed, analyzed, and recomposed to facilitate optimal, transparent decisions. Because the outcome of interest in reintroduction efforts is typically population viability or related metrics, models used in decision analysis efforts for reintroductions will need to include population models. In this special section of the Journal of Wildlife Management, we highlight examples of the construction and use of models for informing management decisions in reintroduced populations. In this introductory contribution, we review concepts in decision analysis, population modeling for analysis of decisions in reintroduction settings, and future directions. Increased use of formal decision analysis, including adaptive management, has great potential to inform reintroduction efforts. Adopting these practices will require close collaboration among managers, decision analysts, population modelers, and field biologists.

  14. RTEL1 polymorphisms are associated with lung cancer risk in the Chinese Han population.

    PubMed

    Yan, Shouchun; Xia, Ridong; Jin, Tianbo; Ren, Hui; Yang, Hua; Li, Jing; Yan, Mengdan; Zhu, Yuanyuan; Chen, Mingwei

    2016-10-25

    RTEL1 (regulator of telomere elongation helicase 1; OMIM 608833) gene polymorphisms were linked to lung cancer (LC) susceptibility in a cancer genome-wide association study (GWAS) Here, we assessed whether seven previously reported RTEL1 polymorphisms influenced LC risk in Han Chinese population. All study samples (554 LC cases and 696 cancer-free controls) were collected from the Affiliated Hospital of Xizang Minzu University in China. We assessed associations between SNPs and LC risk using various several genetic models (codominant, dominant, recessive, overdominant, and additive). Whereas rs2738780 showed a protective effect against LC (Odds ratio (OR) = 0.80 ;95% confidence interval (CI): 0.638 = 0.998; p = 0.048), rs7261546(OR = 4.16; 95% CI: 1.35-12.82; p = 0.007), rs6062299(OR=5.08; 95% CI: 1.43-18.10; p = 0.005) and rs3787098(OR = 5.10; 95% CI: 1.43-18.15; p = 0.004) were all associated with increased LC susceptibility (recessive model). Haplotype analysis suggested that ''CTC'' was associated with a 0.8-fold decrease in LC risk (OR = 0.80, 95% CI, 0.63-1.00; Pearson's p = 0.05). These findings suggest a potential association between RTEL1 polymorphisms and LC risk in a Chinese Han population.

  15. The Bridging Integrator 1 Gene Polymorphism rs744373 and the Risk of Alzheimer's Disease in Caucasian and Asian Populations: An Updated Meta-Analysis.

    PubMed

    Zhu, Ruixia; Liu, Xu; He, Zhiyi

    2017-03-01

    Recent genome-wide association studies have identified an association between the bridging integrator 1 gene (BIN1) rs744373 polymorphism and late-onset Alzheimer's disease (LOAD) in individuals of European ancestry. Additionally, a number of studies have focused on the association between rs744373 and Alzheimer's disease in Caucasian and East Asian populations. However, these results remain inconclusive because of the relatively small sample sizes investigated. Here, we reevaluated this association using samples from seven articles including 22 independent studies comprising 11,832 LOAD patients and 18,133 controls identified by searching PubMed, MEDLINE, and AlzGene databases up to December 2015. We observed no significant heterogeneity between Asian and Caucasian populations. Additive, dominant, and recessive models revealed a significant association between rs744373 and LOAD in the pooled population, while subgroup analysis also identified significant findings in the East Asian population under the additive model (odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.19, P = 0.01) and dominant model (OR = 1.13, 95 % CI 1.03-1.25, P = 0.01), but not under the recessive model. The current meta-analysis further supports previous findings that the rs744373 polymorphism may be associated with LOAD risk in Caucasian and Asian populations. To our knowledge, this is the first large meta-analysis to investigate the association between the rs744373 polymorphism and LOAD in East Asian, American, and European populations.

  16. Joint genotype- and ancestry-based genome-wide association studies in admixed populations.

    PubMed

    Szulc, Piotr; Bogdan, Malgorzata; Frommlet, Florian; Tang, Hua

    2017-09-01

    In genome-wide association studies (GWAS) genetic loci that influence complex traits are localized by inspecting associations between genotypes of genetic markers and the values of the trait of interest. On the other hand, admixture mapping, which is performed in case of populations consisting of a recent mix of two ancestral groups, relies on the ancestry information at each locus (locus-specific ancestry). Recently it has been proposed to jointly model genotype and locus-specific ancestry within the framework of single marker tests. Here, we extend this approach for population-based GWAS in the direction of multimarker models. A modified version of the Bayesian information criterion is developed for building a multilocus model that accounts for the differential correlation structure due to linkage disequilibrium (LD) and admixture LD. Simulation studies and a real data example illustrate the advantages of this new approach compared to single-marker analysis or modern model selection strategies based on separately analyzing genotype and ancestry data, as well as to single-marker analysis combining genotypic and ancestry information. Depending on the signal strength, our procedure automatically chooses whether genotypic or locus-specific ancestry markers are added to the model. This results in a good compromise between the power to detect causal mutations and the precision of their localization. The proposed method has been implemented in R and is available at http://www.math.uni.wroc.pl/~mbogdan/admixtures/. © 2017 WILEY PERIODICALS, INC.

  17. Association between habitual daytime napping and metabolic syndrome: a population-based study.

    PubMed

    Lin, Diaozhu; Sun, Kan; Li, Feng; Qi, Yiqin; Ren, Meng; Huang, Chulin; Tang, Juying; Xue, Shengneng; Li, Yan; Yan, Li

    2014-12-01

    Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P<0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P<0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13-1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P<0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects. Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women. Copyright © 2014. Published by Elsevier Inc.

  18. Evaluation of association between common genetic variants on chromosome 9p21 and coronary artery disease in Turkish population.

    PubMed

    Çakmak, Hüseyin Altuğ; Bayoğlu, Burcu; Durmaz, Eser; Can, Günay; Karadağ, Bilgehan; Cengiz, Müjgan; Vural, Vural Ali; Yüksel, Hüsniye

    2015-03-01

    Coronary artery disease (CAD), which develops from complex interactions between genetic and enviromental factors, is a leading cause of death worldwide. Based on genome-wide association studies (GWAS), the chromosomal region 9p21 has been identified as the most relevant locus presenting a strong association with CAD in different populations. The aim of the present study was to investigate the association of two SNPs on chromosome 9p21 on susceptibility to CAD and the effect of these SNPs along with cardiovascular risk factors on the severity of CAD in the Turkish population. This study had an observational case-control design. We genotyped 460 subjects, aged 30-65 years, to investigate the association of 2 SNPs (rs1333049, rs2383207) on chromosome 9p21 and CAD risk in Turkish population. Real-time polymerase chain reaction (RT-PCR) was used to analyze the 2 SNPs in CAD patients and healthy controls. The genotype and allelic variations of these SNPs with the severity of CAD was also assessed using semi-quantitative methods such as the Gensini score. Student's t test and multiple regression analysis were used for statistical analysis. The SNPs rs1333049 and rs2383207 were found to be associated with CAD with an adjusted OR of 1.81 (95% Cl 1.05-3.12) and 2.12 (95% CI 1.19-4.10) respectively. After adjustment of CAD risk factors such as smoking, family history of CAD and diabetes, the homozygous AA genotype for rs2383207 increased the CAD risk with an OR 3.69. Also a very strong association was found between rs1333049 and rs2383207 and Gensini scores representing the severity of CAD (p<0.001). The rs2383207 and rs1333049 SNPs on 9p21 chromosome were significantly associated with the risk and severity of CAD in the Turkish population.

  19. Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.

    PubMed

    Sundqvist, J; Xu, H; Vodolazkaia, A; Fassbender, A; Kyama, C; Bokor, A; Gemzell-Danielsson, K; D'Hooghe, T M; Falconer, H

    2013-03-01

    Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. Allele frequencies of SNPs were investigated in patients with endometriosis and controls. Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). The inability to confirm all previous findings may result from differences between populations and type II errors. Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation

  20. Diacylglycerol kinase κ (DGKK) variants and hypospadias in Han Chinese: association and meta-analysis.

    PubMed

    Ma, Qichao; Tang, Yunman; Lin, Houwei; Xu, Maosheng; Xu, Guofeng; Fang, Xiaoliang; Chen, Jianhua; Song, Zhijian; Li, Zhiqiang; Shi, Yongyong; Geng, Hongquan

    2015-10-01

    To investigate whether diacylglycerol kinase κ (DGKK) is a susceptibility gene for hypospadias in the Han Chinese population as has been suggested by previous publications. A case-control study involving 466 patients with hypospadias and 402 healthy subjects was conducted to assess the relationship between DGKK single nucleotide polymorphisms (SNPs) and hypospadias risk in the Han Chinese population. The 466 hypospadias patients were further divided into mild, moderate and severe subgroups for analysis. Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs4826632 and rs4599945) were marginally associated with mild and moderate hypospadias [odds ratios (ORs) > 1, P = 0.05 to P < 0.1), whereas no significant relationship was seen with the severe cases (ORs >1, P > 0.1). After correcting for multiple testing, it was determined that neither individual SNPs nor individual haplotypes were associated with hypospadias. To evaluate this relationship in multiple populations, we performed a meta-analysis on six SNPs, using combined data from our present results and those of previous studies of different races (including 1966 patients and 2492 controls). Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs7063116 and rs1934190) were significantly associated with mild/moderate hypospadias (ORs >1, P < 0.05), and rs1934179 was significantly associated with severe hypospadias (OR > 1, P < 0.05). DGKK gene variants do not appear to play a major role in hypospadias susceptibility in the Chinese Han population. Our meta-analysis supports the hypothesis that DGKK is a common risk gene for hypospadias, particularly in cases of mild or moderate hypospadias in Caucasian populations. © 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.

  1. Population-attributable fraction of tubal factor infertility associated with chlamydia.

    PubMed

    Gorwitz, Rachel J; Wiesenfeld, Harold C; Chen, Pai-Lien; Hammond, Karen R; Sereday, Karen A; Haggerty, Catherine L; Johnson, Robert E; Papp, John R; Kissin, Dmitry M; Henning, Tara C; Hook, Edward W; Steinkampf, Michael P; Markowitz, Lauri E; Geisler, William M

    2017-09-01

    Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population-attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiological studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared with White women but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. The objectives of the study were to estimate the population-attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (Black, non-Black) and assess how different definitions of Chlamydia trachomatis seropositivity and tubal factor infertility affect population-attributable fraction estimates. We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL, and Pittsburgh, PA, during October 2012 through June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of 1 and 3 controls per case for Black and non-Black women, respectively. We assessed Chlamydia trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated Chlamydia trachomatis seropositivity and calculated Chlamydia trachomatis-tubal factor infertility odds

  2. Family physicians' ability to perform population management is associated with adoption of other aspects of the patient-centered medical home.

    PubMed

    Ottmar, Jessica; Blackburn, Brenna; Phillips, Robert L; Peterson, Lars E; Jaén, Carlos Roberto

    2015-04-01

    The patient-centered medical home (PCMH) model is considered a promising approach to improving population health, but how elements of these advanced practice models relate to population health capability is unknown. To measure associations between family physicians' performance of population management with PCMH components, a cross-sectional survey was conducted with physicians accessing the American Board of Family Medicine Web site in 2011. Bivariate analysis and logistic regression tested associations between physician and practice demographics and specific PCMH features. The primary outcome was performance of population management. The final sample included 3855 physicians, 37.3% of whom reported performing population management. Demographic characteristics significantly associated with greater use of population management were female sex and graduation from an international medical school. PCMH components that remained associated with population management after adjustment were access to clinical case managers (odds ratio [OR]=2.01, 95% confidence interval [95% CI]: 1.69, 2.39), behavioral health collaboration (OR=1.49, 95% CI: 1.26, 1.77), having an electronic health record that supports meaningful use (OR=1.47, 95% CI: 1.25, 1.74), recent participation in a quality improvement project (OR=2.47, 95% CI: 2.12, 2.89), and routine measurement of patient difficulty securing an appointment (OR=2.87, 95% CI: 2.45, 3.37). Performance of population management was associated with several PCMH elements and resources not present in traditional primary care offices. Attention to these elements likely will enhance delivery of population management services in primary care.

  3. Smoking and Genetic Risk Variation across Populations of European, Asian, and African-American Ancestry - A Meta-analysis of Chromosome 15q25

    PubMed Central

    Chen, Li-Shiun; Saccone, Nancy L.; Culverhouse, Robert C.; Bracci, Paige M.; Chen, Chien-Hsiun; Dueker, Nicole; Han, Younghun; Huang, Hongyan; Jin, Guangfu; Kohno, Takashi; Ma, Jennie Z.; Przybeck, Thomas R.; Sanders, Alan R.; Smith, Jennifer A.; Sung, Yun Ju; Wenzlaff, Angie S.; Wu, Chen; Yoon, Dankyu; Chen, Ying-Ting; Cheng, Yu-Ching; Cho, Yoon Shin; David, Sean P.; Duan, Jubao; Eaton, Charles B.; Furberg, Helena; Goate, Alison M.; Gu, Dongfeng; Hansen, Helen M.; Hartz, Sarah; Hu, Zhibin; Kim, Young Jin; Kittner, Steven J.; Levinson, Douglas F.; Mosley, Thomas H.; Payne, Thomas J.; Rao, DC; Rice, John P.; Rice, Treva K.; Schwantes-An, Tae-Hwi; Shete, Sanjay S.; Shi, Jianxin; Spitz, Margaret R.; Sun, Yan V.; Tsai, Fuu-Jen; Wang, Jen C.; Wrensch, Margaret R.; Xian, Hong; Gejman, Pablo V.; He, Jiang; Hunt, Steven C.; Kardia, Sharon L.; Li, Ming D.; Lin, Dongxin; Mitchell, Braxton D.; Park, Taesung; Schwartz, Ann G.; Shen, Hongbing; Wiencke, John K.; Wu, Jer-Yuarn; Yokota, Jun; Amos, Christopher I.; Bierut, Laura J.

    2012-01-01

    Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day (CPD) phenotype in 27 datasets (European ancestry (N=14,786), Asian (N=6,889), and African American (N=10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (p < 0.01) in each of these three populations (OR=1.33, 95%C.I.=1.25–1.42, p=1.1×10−17 in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments. PMID:22539395

  4. Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.

    PubMed

    Chen, Li-Shiun; Saccone, Nancy L; Culverhouse, Robert C; Bracci, Paige M; Chen, Chien-Hsiun; Dueker, Nicole; Han, Younghun; Huang, Hongyan; Jin, Guangfu; Kohno, Takashi; Ma, Jennie Z; Przybeck, Thomas R; Sanders, Alan R; Smith, Jennifer A; Sung, Yun Ju; Wenzlaff, Angie S; Wu, Chen; Yoon, Dankyu; Chen, Ying-Ting; Cheng, Yu-Ching; Cho, Yoon Shin; David, Sean P; Duan, Jubao; Eaton, Charles B; Furberg, Helena; Goate, Alison M; Gu, Dongfeng; Hansen, Helen M; Hartz, Sarah; Hu, Zhibin; Kim, Young Jin; Kittner, Steven J; Levinson, Douglas F; Mosley, Thomas H; Payne, Thomas J; Rao, D C; Rice, John P; Rice, Treva K; Schwantes-An, Tae-Hwi; Shete, Sanjay S; Shi, Jianxin; Spitz, Margaret R; Sun, Yan V; Tsai, Fuu-Jen; Wang, Jen C; Wrensch, Margaret R; Xian, Hong; Gejman, Pablo V; He, Jiang; Hunt, Steven C; Kardia, Sharon L; Li, Ming D; Lin, Dongxin; Mitchell, Braxton D; Park, Taesung; Schwartz, Ann G; Shen, Hongbing; Wiencke, John K; Wu, Jer-Yuarn; Yokota, Jun; Amos, Christopher I; Bierut, Laura J

    2012-05-01

    Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments. © 2012 Wiley Periodicals, Inc.

  5. Multivariate meta-analysis for non-linear and other multi-parameter associations

    PubMed Central

    Gasparrini, A; Armstrong, B; Kenward, M G

    2012-01-01

    In this paper, we formalize the application of multivariate meta-analysis and meta-regression to synthesize estimates of multi-parameter associations obtained from different studies. This modelling approach extends the standard two-stage analysis used to combine results across different sub-groups or populations. The most straightforward application is for the meta-analysis of non-linear relationships, described for example by regression coefficients of splines or other functions, but the methodology easily generalizes to any setting where complex associations are described by multiple correlated parameters. The modelling framework of multivariate meta-analysis is implemented in the package mvmeta within the statistical environment R. As an illustrative example, we propose a two-stage analysis for investigating the non-linear exposure–response relationship between temperature and non-accidental mortality using time-series data from multiple cities. Multivariate meta-analysis represents a useful analytical tool for studying complex associations through a two-stage procedure. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22807043

  6. Differences in mammographic density between Asian and Caucasian populations: a comparative analysis.

    PubMed

    Rajaram, Nadia; Mariapun, Shivaani; Eriksson, Mikael; Tapia, Jose; Kwan, Pui Yoke; Ho, Weang Kee; Harun, Faizah; Rahmat, Kartini; Czene, Kamila; Taib, Nur Aishah Mohd; Hall, Per; Teo, Soo Hwang

    2017-01-01

    Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors. Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts. Compared to Caucasian women, percent density was 2.0% higher among Asian women (p < 0.001), and dense volume was 5.7 cm 3 higher among pre-menopausal Asian women (p < 0.001). Dense volume was 3.0 cm 3 lower among post-menopausal Asian women (p = 0.009) compared to post-menopausal Caucasian women, and this difference was attributed to population differences in height, weight, and parity (p < 0.001). Our analysis suggests that among post-menopausal women, population differences in mammographic density and risk to breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.

  7. Association between chronic hepatitis C infection and hepatocellular carcinoma in a Scottish population.

    PubMed Central

    Haydon, G H; Jarvis, L M; Simmonds, P; Harrison, D J; Garden, O J; Hayes, P C

    1997-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The geographical prevalence varies considerably in different countries and Scotland is regarded as an area of low risk for the disease. AIMS: To assess the association between chronic hepatitis C infection (HCV) and HCC in a population of patients presenting to a single hospital. PATIENTS: One hundred and fourteen cases of histologically confirmed liver cancer presenting to the Royal Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA. A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was predominant (16 of 20 patients). The time from HCV transmission to development of cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient population, a broader distribution of genotypes was present (genotype 1a: 7; genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002) and demonstrated a significantly shorter duration of infection: range 10-40 years (median: 19). CONCLUSION: There is a strong association between chronic HCV infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The study was unable to distinguish whether the high prevalence of genotype 1b in the HCC population reflected increased oncogenicity in itself, or whether 1b was simply the most prevalent genotype in Scotland when these patients were infected. PMID:9155590

  8. Neo-liberal economic practices and population health: a cross-national analysis, 1980-2004.

    PubMed

    Tracy, Melissa; Kruk, Margaret E; Harper, Christine; Galea, Sandro

    2010-04-01

    Although there has been substantial debate and research concerning the economic impact of neo-liberal practices, there is a paucity of research about the potential relation between neo-liberal economic practices and population health. We assessed the extent to which neo-liberal policies and practices are associated with population health at the national level. We collected data on 119 countries between 1980 and 2004. We measured neo-liberalism using the Fraser Institute's Economic Freedom of the World (EFW) Index, which gives an overall score as well as a score for each of five different aspects of neo-liberal economic practices: (1) size of government, (2) legal structure and security of property rights, (3) access to sound money, (4) freedom to exchange with foreigners and (5) regulation of credit, labor and business. Our measure of population health was under-five mortality. We controlled for potential mediators (income distribution, social capital and openness of political institutions) and confounders (female literacy, total population, rural population, fertility, gross domestic product per capita and time period). In longitudinal multivariable analyses, we found that the EFW index did not have an effect on child mortality but that two of its components: improved security of property rights and access to sound money were associated with lower under-five mortality (p = 0.017 and p = 0.024, respectively). When stratifying the countries by level of income, less regulation of credit, labor and business was associated with lower under-five mortality in high-income countries (p = 0.001). None of the EFW components were significantly associated with under-five mortality in low-income countries. This analysis suggests that the concept of 'neo-liberalism' is not a monolithic entity in its relation to health and that some 'neo-liberal' policies are consistent with improved population health. Further work is needed to corroborate or refute these findings.

  9. Variants and Haplotypes in Angiotensinogen Gene Are Associated With Plasmatic Angiotensinogen Level in Mexican Population

    PubMed Central

    Balam-Ortiz, Eros; Esquivel-Villarreal, Adolfo; Alfaro-Ruiz, Luis; Carrillo, Karol; Elizalde, Adela; Gil, Trinidad; Urushihara, Maki; Kobori, Hiroyuki; Jimenez-Sanchez, Gerardo

    2011-01-01

    Introduction The plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population. Methods Nine polymorphisms in AGT gene were genotyped, and plasma AGT level was determined by enzyme-linked immunosorbent assay. Results Differences in AGT plasma levels were associated with 2 polymorphisms: T-20G, TT = 25.3 ± 8.3 versus TG + GG = 21.6 ± 8.8 μg/mL; P = 0.008 and C3389T (T174M), CC = 25.8 ± 9.9 versus TC + TT = 20.5 ± 5.4 μg/mL; P = 0.0002. Haplotype 2 was associated with low plasma AGT (−5.1 μg/mL [95% confidence interval: −8.6 to −1.6], P = 0.004) and Haplotype 8 was associated with high plasma AGT (6.5 μg/mL [95% confidence interval: 2.5 to 10.6], P = 0.001). This association remained after adjustment for covariates. A Likelihood Ratio Test for haplotype-phenotype association adjusted for covariates resulted in χ2 = 38.9, P = 0.0005. The total effect of the haplotypes on plasma AGT level variance was 19.5%. No association was identified between haplotypes and quantitative traits of blood pressure. Conclusions Two polymorphisms (T-20G and C3389T) and 2 haplotypes (H2 and H8) showed an association with plasma AGT levels in Mexican population. PMID:21629041

  10. TP53 codon 72 polymorphism and susceptibility to cervical cancer in the Chinese population: an update meta-analysis

    PubMed Central

    Li, Bing; Wang, Xin; Chen, Hong; Shang, Li-Xin; Wu, Nan

    2015-01-01

    Background: Although many epidemiologic studies investigated the TP53 codon 72 polymorphism and its association with cervical cancer (CC), definite conclusions cannot be drawn. Aim of the study: To evaluate the association between TP53 codon 72 polymorphism and risk of cervical cancer in the Chinese population. Methods: A computerized literature search was carried out in PubMed, Springer Link, Ovid, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang Database to collect relevant articles. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association. Results: A total of 16 studies including 1684 CC cases and 1178 controls were involved in this meta-analysis. Overall, significant increased association was found between the Pro/Pro carriers and CC risk when all studies in Chinese population pooled into the meta-analysis (heterozygous model: OR = 1.22, 95% CI: 1.01-1.46). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Han and in hospital-based studies. Conclusion: Our results suggest that the TP53 codon 72 polymorphism may be potential biomarkers for CC risk in the Chinese population, especially for Han Chinese, and studies with wider spectrum of population are required for definite conclusions. PMID:26309559

  11. Associations between matrix metalloproteinase gene polymorphisms and glaucoma susceptibility: a meta-analysis.

    PubMed

    Wu, Ming-Yue; Wu, Yang; Zhang, Yong; Liu, Cai-Yun; Deng, Chun-Yan; Peng, Le; Zhou, Lan

    2017-04-21

    Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I 2  = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I 2  = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I 2  = 0%). Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

  12. Aphid Species and Population Dynamics Associated with Strawberry.

    PubMed

    Bernardi, D; Araujo, E S; Zawadneak, M A C; Botton, M; Mogor, A F; Garcia, M S

    2013-12-01

    Aphids are among the major pests associated with strawberries in Southern Brasil. In this study, we identified the main species that occur in strawberry fields in the states of Paraná and Rio Grande do Sul, Brasil. We also compared the effectiveness of different sampling methods and studied the population dynamics of aphid species during two strawberry crop cycles in the municipality of Pinhais, state of Paraná, Brasil. Chaetosiphon fragaefolii (Cockerell) and Aphis forbesi Weed were the main species associated with strawberry. The method of hit plant and the Möericke trap showed equal effectiveness to capture wingless and winged insects. The peak population of aphids in the state of Paraná occurred from September to November. This information can help producers to implement strategies to monitor and control the major aphid species that occur in strawberry culture.

  13. A positive association between anxiety disorders and cannabis use or cannabis use disorders in the general population- a meta-analysis of 31 studies

    PubMed Central

    2014-01-01

    Background The aim of the current study was to investigate the association between anxiety and cannabis use/cannabis use disorders in the general population. Methods A total of N = 267 studies were identified from a systematic literature search (any time- March 2013) of Medline and PsycInfo databases, and a hand search. The results of 31 studies (with prospective cohort or cross-sectional designs using non-institutionalised cases) were analysed using a random-effects meta-analysis with the inverse variance weights. Lifetime or past 12-month cannabis use, anxiety symptoms, and cannabis use disorders (CUD; dependence and/or abuse/harmful use) were classified according to DSM/ICD criteria or scores on standardised scales. Results There was a small positive association between anxiety and either cannabis use (OR = 1.24, 95% CI: 1.06-1.45, p = .006; N = 15 studies) or CUD (OR = 1.68, 95% CI: 1.23-2.31, p = .001; N = 13 studies), and between comorbid anxiety + depression and cannabis use (OR = 1.68, 95% CI: 1.17-2.40, p = .004; N = 5 studies). The positive associations between anxiety and cannabis use (or CUD) were present in subgroups of studies with ORs adjusted for possible confounders (substance use, psychiatric illness, demographics) and in studies with clinical diagnoses of anxiety. Cannabis use at baseline was significantly associated with anxiety at follow-up in N = 5 studies adjusted for confounders (OR = 1.28, 95% CI: 1.06-1.54, p = .01). The opposite relationship was investigated in only one study. There was little evidence for publication bias. Conclusion Anxiety is positively associated with cannabis use or CUD in cohorts drawn from some 112,000 non-institutionalised members of the general population of 10 countries. PMID:24884989

  14. 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

  15. Landscape genomics and pathway analysis to understand genetic adaptation of South African indigenous goat populations.

    PubMed

    Mdladla, K; Dzomba, E F; Muchadeyi, F C

    2018-04-01

    In Africa, extensively raised livestock populations in most smallholder farming communities are exposed to harsh and heterogeneous climatic conditions and disease pathogens that they adapt to in order to survive. Majority of these livestock species, including goats, are of non-descript and uncharacterized breeds and their response to natural selection presented by heterogeneous environments is still unresolved. This study investigated genetic diversity and its association with environmental and geographic conditions in 194 South African indigenous goats from different geographic locations genotyped on the Illumina goat SNP50K panel. Population structure analysis revealed a homogeneous genetic cluster of the Tankwa goats, restricted to the Northern Cape province. Overall, the Boer, Kalahari Red, and Savanna showed a wide geographic spread of shared genetic components, whereas the village ecotypes revealed a longitudinal distribution. The relative importance of environmental factors on genetic variation of goat populations was assessed using redundancy analysis (RDA). Climatic and geographic variables explained 22% of the total variation while climatic variables alone accounted for 17% of the diversity. Geographic variables solitarily explained 1% of the total variation. The first axis (Model I) of the RDA analysis revealed 329 outlier SNPs. Landscape genomic approaches of spatial analysis method (SAM) identified a total of 843 (1.75%) SNPs, while latent factor mixed models (LFMM) identified 714 (1.48%) SNPs significantly associated with environmental variables. Significant markers were within genes involved in biological functions potentially important for environmental adaptation. Overall, the study suggested environmental factors to have some effect in shaping the genetic variation of South African indigenous goat populations. Loci observed to be significant and under selection may be responsible for the adaption of the goat populations to local production systems.

  16. Genome-wide association analysis for feed efficiency in Angus cattle.

    PubMed

    Rolf, M M; Taylor, J F; Schnabel, R D; McKay, S D; McClure, M C; Northcutt, S L; Kerley, M S; Weaber, R L

    2012-08-01

    Estimated breeding values for average daily feed intake (AFI; kg/day), residual feed intake (RFI; kg/day) and average daily gain (ADG; kg/day) were generated using a mixed linear model incorporating genomic relationships for 698 Angus steers genotyped with the Illumina BovineSNP50 assay. Association analyses of estimated breeding values (EBVs) were performed for 41,028 single nucleotide polymorphisms (SNPs), and permutation analysis was used to empirically establish the genome-wide significance threshold (P < 0.05) for each trait. SNPs significantly associated with each trait were used in a forward selection algorithm to identify genomic regions putatively harbouring genes with effects on each trait. A total of 53, 66 and 68 SNPs explained 54.12% (24.10%), 62.69% (29.85%) and 55.13% (26.54%) of the additive genetic variation (when accounting for the genomic relationships) in steer breeding values for AFI, RFI and ADG, respectively, within this population. Evaluation by pathway analysis revealed that many of these SNPs are in genomic regions that harbour genes with metabolic functions. The presence of genetic correlations between traits resulted in 13.2% of SNPs selected for AFI and 4.5% of SNPs selected for RFI also being selected for ADG in the analysis of breeding values. While our study identifies panels of SNPs significant for efficiency traits in our population, validation of all SNPs in independent populations will be necessary before commercialization. © 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.

  17. Prevalence and cost of HIV-associated weight loss in a managed care population.

    PubMed

    Siddiqui, Javeed; Phillips, Amy L; Freedland, Eric S; Sklar, Ami R; Darkow, Theodore; Harley, Carolyn R

    2009-05-01

    To estimate the prevalence of HIV-associated weight loss among HIV patients in a US managed care population, and compare demographic and clinical characteristics of HIV patients with and without evidence of HIV-associated weight loss. A retrospective observational study was conducted using a large, geographically diverse US managed care population to identify commercial enrollees with HIV/AIDS from 1/1/2005-7/31/2007, based on a combination of HIV/AIDS diagnosis codes or antiretroviral treatment. HIV-associated weight loss status was defined according to an algorithm combining evidence for weight loss-associated conditions, anorexia symptoms, and various treatments for weight loss or wasting. Among HIV patients continuously enrolled in the health plan for one year, patient demographics, treatments, and comorbidities were compared between patients with and without evidence for weight loss. A total of 22,535 patients with HIV/AIDS were identified, including 2098 who met the criteria for weight loss (estimated prevalence 9.3%; 95% CI: 8.9% - 9.7%). Among 12,187 continuously enrolled patients with HIV, 1006 (8.3%) had evidence of HIV-associated weight loss. Patients with HIV-associated weight loss were older (44.1 vs. 42.6 years), and more men had HIV-associated weight loss than women (8.8% vs. 5.3%). A number of comorbidities were more common among patients with HIV-associated weight loss. On average, these patients also had more ambulatory (24.0 vs. 13.4), ER (1.4 vs. 0.8), and inpatient visits (0.5 vs. 0.1). Total annual health care costs for patients with HIV-associated weight loss were more than double (mean $45,686 vs. $19,960) the costs for HIV patients without weight loss. Despite the availability of effective antiretroviral therapy, weight loss remains a problem among patients with HIV. Based on this analysis, almost 1 in 10 managed care patients with HIV have evidence of HIV-associated weight loss. These patients tend to have more comorbidities, use more

  18. Identification of TNIP1 Polymorphisms by High Resolution Melting Analysis with Unlabelled Probe: Association with Systemic Lupus Erythematosus

    PubMed Central

    Zhang, Jie; Chen, Yuewen; Shao, Yong; Wu, Qi; Guan, Ming; Zhang, Wei; Wan, Jun; Yu, Bo

    2012-01-01

    Background. TNFα-induced protein 3 (TNFAIP3) interacting with protein 1 (TNIP1) acts as a negative regulator of NF-κB and plays an important role in maintaining the homeostasis of immune system. A recent genome-wide association study (GWAS) showed that the polymorphism of TNIP1 was associated with the disease risk of SLE in Caucasian. In this study, we investigated whether the association of TNIP1 with SLE was replicated in Chinese population. Methods. The association of TNIP1 SNP rs7708392 (G/C) was determined by high resolution melting (HRM) analysis with unlabeled probe in 285 SLE patients and 336 healthy controls. Results. A new SNP rs79937737 located on 5 bp upstream of rs7708392 was discovered during the HRM analysis. No association of rs7708392 or rs79937737 with the disease risk of SLE was found. Furthermore, rs7708392 and rs79937737 were in weak linkage disequilibrium (LD). Hypotypes analysis of the two SNPs also showed no association with SLE in Chinese population. Conclusions. High resolution melting analysis with unlabeled probes proves to be a powerful and efficient genotyping method for identifying and screening SNPs. No association of rs7708392 or rs79937737 with the disease risk of SLE was observed in Chinese population. PMID:22852072

  19. 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.

  20. Cerebral Small Vessel Disease Burden Is Associated with Motor Performance of Lower and Upper Extremities in Community-Dwelling Populations

    PubMed Central

    Su, Ning; Zhai, Fei-Fei; Zhou, Li-Xin; Ni, Jun; Yao, Ming; Li, Ming-Li; Jin, Zheng-Yu; Gong, Gao-Lang; Zhang, Shu-Yang; Cui, Li-Ying; Tian, Feng; Zhu, Yi-Cheng

    2017-01-01

    Objective: To investigate the correlation between cerebral small vessel disease (CSVD) burden and motor performance of lower and upper extremities in community-dwelling populations. Methods: We performed a cross-sectional analysis on 770 participants enrolled in the Shunyi study, which is a population-based cohort study. CSVD burden, including white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), perivascular spaces (PVS), and brain atrophy were measured using 3T magnetic resonance imaging. All participants underwent quantitative motor assessment of lower and upper extremities, which included 3-m walking speed, 5-repeat chair-stand time, 10-repeat pronation–supination time, and 10-repeat finger-tapping time. Data on demographic characteristics, vascular risk factors, and cognitive functions were collected. General linear model analysis was performed to identify potential correlations between motor performance measures and imaging markers of CSVD after controlling for confounding factors. Results: For motor performance of the lower extremities, WMH was negatively associated with gait speed (standardized β = -0.092, p = 0.022) and positively associated with chair-stand time (standardized β = 0.153, p < 0.0001, surviving FDR correction). For motor performance of the upper extremities, pronation–supination time was positively associated with WMH (standardized β = 0.155, p < 0.0001, surviving FDR correction) and negatively with brain parenchymal fraction (BPF; standardized β = -0.125, p = 0.011, surviving FDR correction). Only BPF was found to be negatively associated with finger-tapping time (standardized β = -0.123, p = 0.012). However, lacunes, CMBs, or PVS were not found to be associated with motor performance of lower or upper extremities in multivariable analysis. Conclusion: Our findings suggest that cerebral microstructural changes related to CSVD may affect motor performance of both lower and upper extremities. WMH and brain

  1. Cerebral Small Vessel Disease Burden Is Associated with Motor Performance of Lower and Upper Extremities in Community-Dwelling Populations.

    PubMed

    Su, Ning; Zhai, Fei-Fei; Zhou, Li-Xin; Ni, Jun; Yao, Ming; Li, Ming-Li; Jin, Zheng-Yu; Gong, Gao-Lang; Zhang, Shu-Yang; Cui, Li-Ying; Tian, Feng; Zhu, Yi-Cheng

    2017-01-01

    Objective: To investigate the correlation between cerebral small vessel disease (CSVD) burden and motor performance of lower and upper extremities in community-dwelling populations. Methods: We performed a cross-sectional analysis on 770 participants enrolled in the Shunyi study, which is a population-based cohort study. CSVD burden, including white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), perivascular spaces (PVS), and brain atrophy were measured using 3T magnetic resonance imaging. All participants underwent quantitative motor assessment of lower and upper extremities, which included 3-m walking speed, 5-repeat chair-stand time, 10-repeat pronation-supination time, and 10-repeat finger-tapping time. Data on demographic characteristics, vascular risk factors, and cognitive functions were collected. General linear model analysis was performed to identify potential correlations between motor performance measures and imaging markers of CSVD after controlling for confounding factors. Results: For motor performance of the lower extremities, WMH was negatively associated with gait speed (standardized β = -0.092, p = 0.022) and positively associated with chair-stand time (standardized β = 0.153, p < 0.0001, surviving FDR correction). For motor performance of the upper extremities, pronation-supination time was positively associated with WMH (standardized β = 0.155, p < 0.0001, surviving FDR correction) and negatively with brain parenchymal fraction (BPF; standardized β = -0.125, p = 0.011, surviving FDR correction). Only BPF was found to be negatively associated with finger-tapping time (standardized β = -0.123, p = 0.012). However, lacunes, CMBs, or PVS were not found to be associated with motor performance of lower or upper extremities in multivariable analysis. Conclusion: Our findings suggest that cerebral microstructural changes related to CSVD may affect motor performance of both lower and upper extremities. WMH and brain atrophy

  2. Association of Problem Gambling with Type of Gambling Among Italian General Population.

    PubMed

    Scalese, Marco; Bastiani, Luca; Salvadori, Stefano; Gori, Mercedes; Lewis, Isabella; Jarre, Paolo; Molinaro, Sabrina

    2016-09-01

    The origin of gambling disorders is uncertain; however, research has shown a tendency to focus on specific types of games as a potential important risk factor. The principal aim of this study is to examine the relationships between types of gambling practices and gambling disorder. The data were extracted from IPSAD-Italia(®) 2010-2011 (Italian Population Survey on Alcohol and other Drugs), a survey among the Italian general population which collects socio-cultural information, information about the use of drugs, legal substances and gambling habits. In order to identify the "problem gambler" we used the Problem Gambling Severity Index. Three groups are considered in this analysis: no-risk gamblers, low-risk gamblers, moderate-risk/problem gamblers. Type of gambling practice was considered among two types of gambler: one-game players and multi-games players. 1.9 % of multi-game players were considered problem gamblers, only 0.6 % of one-game players were problem gamblers (p < 0.001). The percentage of players who were low and moderate-risk gamblers was approximately double among multi-game players, with 14.4 % low-risk and 5.8 % moderate-risk; compared with 7.7 % low-risk and 2.5 % moderate risk among one-game players. Results of ordinal logistic regression analysis confirmed that higher level of gambling severity was associated with multi-game players (OR = 2.23, p < 0.0001). Video-poker/slot-machines show the highest association with gambling severity among both one-game players and multi-game players, with scores of OR equal to 4.3 and 4.5 respectively. These findings suggest a popular perception of risk associated with this type of gambling for the development of gambling problems.

  3. Population analysis of the cingulum bundle using the tubular surface model for schizophrenia detection

    NASA Astrophysics Data System (ADS)

    Mohan, Vandana; Sundaramoorthi, Ganesh; Kubicki, Marek; Terry, Douglas; Tannenbaum, Allen

    2010-03-01

    We propose a novel framework for population analysis of DW-MRI data using the Tubular Surface Model. We focus on the Cingulum Bundle (CB) - a major tract for the Limbic System and the main connection of the Cingulate Gyrus, which has been associated with several aspects of Schizophrenia symptomatology. The Tubular Surface Model represents a tubular surface as a center-line with an associated radius function. It provides a natural way to sample statistics along the length of the fiber bundle and reduces the registration of fiber bundle surfaces to that of 4D curves. We apply our framework to a population of 20 subjects (10 normal, 10 schizophrenic) and obtain excellent results with neural network based classification (90% sensitivity, 95% specificity) as well as unsupervised clustering (k-means). Further, we apply statistical analysis to the feature data and characterize the discrimination ability of local regions of the CB, as a step towards localizing CB regions most relevant to Schizophrenia.

  4. Genome-wide association of body fat distribution in African ancestry populations suggests new loci.

    PubMed

    Liu, Ching-Ti; Monda, Keri L; Taylor, Kira C; Lange, Leslie; Demerath, Ellen W; Palmas, Walter; Wojczynski, Mary K; Ellis, Jaclyn C; Vitolins, Mara Z; Liu, Simin; Papanicolaou, George J; Irvin, Marguerite R; Xue, Luting; Griffin, Paula J; Nalls, Michael A; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A; Chen, Wei-Min; Chen, Fang; Henderson, Brian E; Millikan, Robert C; Ambrosone, Christine B; Strom, Sara S; Guo, Xiuqing; Andrews, Jeanette S; Sun, Yan V; Mosley, Thomas H; Yanek, Lisa R; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I; Speliotes, Elizabeth K; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V; Britton, Angela F; Zonderman, Alan B; Rasmussen-Torvik, Laura J; Chen, Yii-Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B; Zhao, Wei; Peyser, Patricia A; Kardia, Sharon L R; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, Joann E; Kuller, Lewis H; Ochs-Balcom, Heather M; Johnson, Karen C; Sucheston, Lara; Ordovas, Jose M; Palmer, Julie R; Haiman, Christopher A; McKnight, Barbara; Howard, Barbara V; Becker, Diane M; Bielak, Lawrence F; Liu, Yongmei; Allison, Matthew A; Grant, Struan F A; Burke, Gregory L; Patel, Sanjay R; Schreiner, Pamela J; Borecki, Ingrid B; Evans, Michele K; Taylor, Herman; Sale, Michele M; Howard, Virginia; Carlson, Christopher S; Rotimi, Charles N; Cushman, Mary; Harris, Tamara B; Reiner, Alexander P; Cupples, L Adrienne; North, Kari E; Fox, Caroline S

    2013-01-01

    Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0 × 10(-6) were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5 × 10(-8); RREB1: p = 5.7 × 10(-8)). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept

  5. Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

    PubMed Central

    Lange, Leslie; Demerath, Ellen W.; Palmas, Walter; Wojczynski, Mary K.; Ellis, Jaclyn C.; Vitolins, Mara Z.; Liu, Simin; Papanicolaou, George J.; Irvin, Marguerite R.; Xue, Luting; Griffin, Paula J.; Nalls, Michael A.; Adeyemo, Adebowale; Liu, Jiankang; Li, Guo; Ruiz-Narvaez, Edward A.; Chen, Wei-Min; Chen, Fang; Henderson, Brian E.; Millikan, Robert C.; Ambrosone, Christine B.; Strom, Sara S.; Guo, Xiuqing; Andrews, Jeanette S.; Sun, Yan V.; Mosley, Thomas H.; Yanek, Lisa R.; Shriner, Daniel; Haritunians, Talin; Rotter, Jerome I.; Speliotes, Elizabeth K.; Smith, Megan; Rosenberg, Lynn; Mychaleckyj, Josyf; Nayak, Uma; Spruill, Ida; Garvey, W. Timothy; Pettaway, Curtis; Nyante, Sarah; Bandera, Elisa V.; Britton, Angela F.; Zonderman, Alan B.; Rasmussen-Torvik, Laura J.; Chen, Yii-Der Ida; Ding, Jingzhong; Lohman, Kurt; Kritchevsky, Stephen B.; Zhao, Wei; Peyser, Patricia A.; Kardia, Sharon L. R.; Kabagambe, Edmond; Broeckel, Ulrich; Chen, Guanjie; Zhou, Jie; Wassertheil-Smoller, Sylvia; Neuhouser, Marian L.; Rampersaud, Evadnie; Psaty, Bruce; Kooperberg, Charles; Manson, JoAnn E.; Kuller, Lewis H.; Ochs-Balcom, Heather M.; Johnson, Karen C.; Sucheston, Lara; Ordovas, Jose M.; Palmer, Julie R.; Haiman, Christopher A.; McKnight, Barbara; Howard, Barbara V.; Becker, Diane M.; Bielak, Lawrence F.; Liu, Yongmei; Allison, Matthew A.; Grant, Struan F. A.; Burke, Gregory L.; Patel, Sanjay R.; Schreiner, Pamela J.; Borecki, Ingrid B.; Evans, Michele K.; Taylor, Herman; Sale, Michele M.; Howard, Virginia; Carlson, Christopher S.; Rotimi, Charles N.; Cushman, Mary; Harris, Tamara B.; Reiner, Alexander P.; Cupples, L. Adrienne; North, Kari E.; Fox, Caroline S.

    2013-01-01

    Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce

  6. Improved score statistics for meta-analysis in single-variant and gene-level association studies.

    PubMed

    Yang, Jingjing; Chen, Sai; Abecasis, Gonçalo

    2018-06-01

    Meta-analysis is now an essential tool for genetic association studies, allowing them to combine large studies and greatly accelerating the pace of genetic discovery. Although the standard meta-analysis methods perform equivalently as the more cumbersome joint analysis under ideal settings, they result in substantial power loss under unbalanced settings with various case-control ratios. Here, we investigate the power loss problem by the standard meta-analysis methods for unbalanced studies, and further propose novel meta-analysis methods performing equivalently to the joint analysis under both balanced and unbalanced settings. We derive improved meta-score-statistics that can accurately approximate the joint-score-statistics with combined individual-level data, for both linear and logistic regression models, with and without covariates. In addition, we propose a novel approach to adjust for population stratification by correcting for known population structures through minor allele frequencies. In the simulated gene-level association studies under unbalanced settings, our method recovered up to 85% power loss caused by the standard methods. We further showed the power gain of our methods in gene-level tests with 26 unbalanced studies of age-related macular degeneration . In addition, we took the meta-analysis of three unbalanced studies of type 2 diabetes as an example to discuss the challenges of meta-analyzing multi-ethnic samples. In summary, our improved meta-score-statistics with corrections for population stratification can be used to construct both single-variant and gene-level association studies, providing a useful framework for ensuring well-powered, convenient, cross-study analyses. © 2018 WILEY PERIODICALS, INC.

  7. 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

  8. Combinations of bacterial species associated with symptomatic endodontic infections in a Chinese population.

    PubMed

    Qi, Z; Cao, H; Jiang, H; Zhao, J; Tang, Z

    2016-01-01

    To use microarrays to detect 11 selected bacteria in infected root canals, revealing bacterial combinations that are associated with clinical symptoms and signs of primary endodontic infections in a Chinese population. DNA was extracted from 90 samples collected from the root canals of teeth with primary endodontic infections in a Chinese population, and the 16S rRNA gene was amplified by polymerase chain reaction (PCR). The PCR products were hybridized to microarrays containing specific oligonucleotide probes targeting 11 species, and the arrays were screened with a confocal laser scanner. Pearson's chi-squared test and cluster analysis were performed to investigate the associations between the bacterial combinations and clinical symptoms and signs using SAS 8.02. Seventy-seven samples (86%) yielded at least one of the 11 target species. Parvimonas micra (56%), Porphyromonas endodontalis (51%), Tannerella forsythia (48%), Prevotella intermedia (44%) and Porphyromonas gingivalis (37%) were the most prevalent taxa and were often concomitant. The following positive associations were found between the bacterial combinations and clinical features: P. endodontalis and T. forsythia with abscess; P. gingivalis and P. micra with sinus tract; P. gingivalis and P. endodontalis or P. micra and P. endodontalis with abscess and sinus tract; and the combination of P. endodontalis, P. micra, T. forsythia and P. gingivalis with sinus tract (P < 0.05). Various combinations of P. micra, P. endodontalis, T. forsythia and P. gingivalis may contribute to abscesses or sinus tracts of endodontic origin with bacterial synergism in a Chinese population. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  9. RTEL1 polymorphisms are associated with lung cancer risk in the Chinese Han population

    PubMed Central

    Yan, Shouchun; Xia, Ridong; Jin, Tianbo; Ren, Hui; Yang, Hua; Li, Jing; Yan, Mengdan; Zhu, Yuanyuan; Chen, Mingwei

    2016-01-01

    RTEL1 (regulator of telomere elongation helicase 1; OMIM 608833) gene polymorphisms were linked to lung cancer (LC) susceptibility in a cancer genome-wide association study (GWAS) Here, we assessed whether seven previously reported RTEL1 polymorphisms influenced LC risk in Han Chinese population. All study samples (554 LC cases and 696 cancer-free controls) were collected from the Affiliated Hospital of Xizang Minzu University in China. We assessed associations between SNPs and LC risk using various several genetic models (codominant, dominant, recessive, overdominant, and additive). Whereas rs2738780 showed a protective effect against LC (Odds ratio (OR) = 0.80 ;95% confidence interval (CI): 0.638 = 0.998; p = 0.048), rs7261546(OR = 4.16; 95% CI: 1.35–12.82; p = 0.007), rs6062299(OR=5.08; 95% CI: 1.43–18.10; p = 0.005) and rs3787098(OR = 5.10; 95% CI: 1.43–18.15; p = 0.004) were all associated with increased LC susceptibility (recessive model). Haplotype analysis suggested that “CTC” was associated with a 0.8-fold decrease in LC risk (OR = 0.80, 95% CI, 0.63–1.00; Pearson's p = 0.05). These findings suggest a potential association between RTEL1 polymorphisms and LC risk in a Chinese Han population. PMID:27765928

  10. Association of the leptin-to-adiponectin ratio with metabolic syndrome in a sub-Saharan African population.

    PubMed

    Ayina, Clarisse Noël A; Endomba, Francky Teddy A; Mandengue, Samuel Honoré; Noubiap, Jean Jacques N; Ngoa, Laurent Serge Etoundi; Boudou, Philippe; Gautier, Jean-François; Mbanya, Jean Claude; Sobngwi, Eugene

    2017-01-01

    Worldwide there is an increased prevalence of metabolic syndrome mainly due to life-style modifications, and Africans are not saved of this situation. Many markers have been studied to predict the risk of this syndrome but the most used are leptin and adiponectin. Data on these metabolic markers are scare in Africa and this study aimed to assess the association between the leptin-to-adiponectin ratio (LAR) with metabolic syndrome in a Cameroonian population. This was a cross-sectional study that included 476 adults among a general population of Cameroon. Data collected concerned the body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). To assess correlations we used Spearman's analyses and association of the studied variables with metabolic syndrome were done using binary logistic regression analysis. The leptin to adiponectin ratio was significantly and positively correlated with the body mass index (r = 0.669, p < 0.0001), waist circumference (r = 0.595, p < 0.0001), triglycerides (r = 0.190, p = 0.001), insulin levels (r = 0.333, p < 0.0001) and HOMA-IR (r = 0.306, p < 0.0001). Binary logistic regression analysis revealed that leptin, adiponectin and LAR were significantly associated with metabolic syndrome with respective unadjusted OR of 1.429, 0.468 and 1.502. After adjustment, for age and sex, the associations remained significative; LAR was also found to be significantly associated with metabolic syndrome (OR = 1.573, p value =0.000) as well as lower levels of adiponectin (OR = 0.359, p value =0.000) and higher levels of leptin (OR = 1.469, p value =0.001). This study revealed that LAR is significantly associated with metabolic syndrome in sub-Saharan African population, independently to age and sex.

  11. Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study.

    PubMed

    Carlson, Christopher S; Matise, Tara C; North, Kari E; Haiman, Christopher A; Fesinmeyer, Megan D; Buyske, Steven; Schumacher, Fredrick R; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D; Duggan, David J; Spencer, Kylee L; Dumitrescu, Logan; Eaton, Charles B; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C; Hindorff, Lucia A; Kooperberg, Charles L

    2013-09-01

    The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification

  12. Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study

    PubMed Central

    Carlson, Christopher S.; Matise, Tara C.; North, Kari E.; Haiman, Christopher A.; Fesinmeyer, Megan D.; Buyske, Steven; Schumacher, Fredrick R.; Peters, Ulrike; Franceschini, Nora; Ritchie, Marylyn D.; Duggan, David J.; Spencer, Kylee L.; Dumitrescu, Logan; Eaton, Charles B.; Thomas, Fridtjof; Young, Alicia; Carty, Cara; Heiss, Gerardo; Le Marchand, Loic; Crawford, Dana C.; Hindorff, Lucia A.; Kooperberg, Charles L.

    2013-01-01

    The vast majority of genome-wide association study (GWAS) findings reported to date are from populations with European Ancestry (EA), and it is not yet clear how broadly the genetic associations described will generalize to populations of diverse ancestry. The Population Architecture Using Genomics and Epidemiology (PAGE) study is a consortium of multi-ancestry, population-based studies formed with the objective of refining our understanding of the genetic architecture of common traits emerging from GWAS. In the present analysis of five common diseases and traits, including body mass index, type 2 diabetes, and lipid levels, we compare direction and magnitude of effects for GWAS-identified variants in multiple non-EA populations against EA findings. We demonstrate that, in all populations analyzed, a significant majority of GWAS-identified variants have allelic associations in the same direction as in EA, with none showing a statistically significant effect in the opposite direction, after adjustment for multiple testing. However, 25% of tagSNPs identified in EA GWAS have significantly different effect sizes in at least one non-EA population, and these differential effects were most frequent in African Americans where all differential effects were diluted toward the null. We demonstrate that differential LD between tagSNPs and functional variants within populations contributes significantly to dilute effect sizes in this population. Although most variants identified from GWAS in EA populations generalize to all non-EA populations assessed, genetic models derived from GWAS findings in EA may generate spurious results in non-EA populations due to differential effect sizes. Regardless of the origin of the differential effects, caution should be exercised in applying any genetic risk prediction model based on tagSNPs outside of the ancestry group in which it was derived. Models based directly on functional variation may generalize more robustly, but the identification

  13. Customized versus Population Fetal Growth Norms and Adverse Outcomes Associated with Small for Gestational Age Infants in a High-Risk Cohort.

    PubMed

    Moussa, Hind N; Wu, Zhao Helen; Han, Yimei; Pacheco, Luis D; Blackwell, Sean C; Sibai, Baha M; Saade, George; Costantine, Maged M

    2015-06-01

    To compare population versus customized fetal growth norms in identifying neonates at risk for adverse perinatal and neonatal outcomes (AOs) associated with small for gestational age (SGA) in high-risk women. Secondary analysis to a multicenter treatment trial of pregnant women at high risk for preeclampsia using low-dose aspirin versus placebo. The associations between SGA by population (SGApop) and customized (SGAcust) norms and AOs were evaluated. A total of 2,289 mother/infant pairs were included in the analysis. The rates of SGA in the aspirin and placebo groups were similar by the customized (22.8% vs 23.9%; p = 0.55) or population (8.7% vs 7.5%; p = 0.54) norms; however, they were lower using population norms compared with customized norms (p < 0.001). SGAcust, but not SGApop, was associated with spontaneous preterm birth (odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.15-1.81; p < 0.001), preterm premature rupture of membranes (OR 1.42 95% CI 1.05-1.92; p = 0.02), and cesarean delivery (OR: 1.35, 95% CI: 1.11-1.64; p = 0.002). Both SGAcust and SGApop were associated with the composite neonatal outcome, indicated preterm delivery before 32, 35, and 37 weeks, oligohydramnios, fetal distress, as well as decreased risk of oxygen requirement. Neither was associated with preeclampsia. Customized approach for assessment of fetal growth was associated with higher SGA rates and better identification of SGA neonates at risk for AOs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Prevalence of associated extracardiac malformations in the congenital heart disease population.

    PubMed

    Egbe, Alexander; Uppu, Santosh; Lee, Simon; Ho, Deborah; Srivastava, Shubhika

    2014-10-01

    The authors hypothesized that changes in prenatal factors such as termination of pregnancy for fetal anomalies and prenatal vitamin supplementation have altered the epidemiology of patients with multiple congenital anomalies and may have had an impact on their prevalence in the current era. This study reviewed the Nationwide Inpatient Sample database from 1998 to 2008 and compared the prevalence of ECM among live births with a CHD diagnosis (case) and that among live births without a CHD diagnosis (control). For this study, 42 ECM and 10 CHD diagnoses were selected for subanalysis. Longitudinal analysis also was performed to determine temporal variation of ECM prevalence in the CHD population during the 11-year study period. The cohort in this study consisted of 97,154 patients in the case group and 12,078,482 subjects in the control group. The prevalences in the CHD population were 11.4 % for nonsyndromic congenital malformation (NSCM), 2.2 % for genetic syndrome (GS), and 13.6 % for overall extracardiac congenital malformation (ECM). The prevalences in the control group were 6.7 % for NSCM, 0.3 % for GS, and 7.0 % for ECM. The findings showed a strong association of NSCM [odds ratio (OR) 1.88; 95 % confidence interval (CI) 1.73-1.94], GS (OR 2.52; 95 % CI 2.44-2.61), and overall ECM (OR 2.01; 95 % CI 1.97-2.14) with CHD. The prevalences of GS and multiple organ system CM decreased significantly during the study period. This study was the largest and most comprehensive population-based study to evaluate the association between CHD and ECM in newborns.

  15. Population structure and linkage disequilibrium in Lupinus albus L. germplasm and its implication for association mapping.

    PubMed

    Iqbal, Muhammad Javed; Mamidi, Sujan; Ahsan, Rubina; Kianian, Shahryar F; Coyne, Clarice J; Hamama, Anwar A; Narina, Satya S; Bhardwaj, Harbans L

    2012-08-01

    White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized for its ability to grow on poor soils and application as green manure in addition to seed harvest. The seed has very high levels of protein (33-47 %) and oil (6-13 %). It also has many secondary metabolites that are potentially of nutraceutical value to animals and humans. Despite such a great potential, lupins role in modern agriculture began only in the twentieth century. Although a large collection of Lupinus germplasm accessions is available worldwide, rarely have they been genetically characterized. Additionally, scarce genomic resources in terms of recombinant populations and genome information have been generated for L. albus. With the advancement in association mapping methods, the natural populations have the potential to replace the recombinant populations in gene mapping and marker-trait associations. Therefore, we studied the genetic similarity, population structure and marker-trait association in a USDA germplasm collection for their current and future application in this crop improvement. A total of 122 PI (Plant Inventory) lines were screened with 18 AFLP primer pairs that generated 2,277 fragments. A subset of 892 polymorphic markers with MAF >0.05 (minor allele frequency) were used for association mapping. The cluster analysis failed to group accessions on the basis of their passport information, and a weak structure and low linkage disequilibrium (LD) were observed indicating the usefulness of the collection for association mapping. Moreover, we were also able to identify two markers (a p value of 1.53 × 10(-4) and 2.3 × 10(-4)) that explained 22.69 and 20.5 % of seed weight variation determined using R (LR) (2) . The implications of lack of geographic clustering, population structure, low LD and the ability of AFLP to map seed weight trait using association mapping and the usefulness of the PI collections in breeding programs are discussed.

  16. Association study between GAS6 gene polymorphisms and risk of preeclampsia in Chinese population.

    PubMed

    Ye, Liyan; Guan, Linbo; Fan, Ping; Liu, Xinghui; Liu, Rui; Chen, Jinxin; Zhu, Yue; Wei, Xing; Liu, Yu; Bai, Huai

    2017-04-01

    Preeclampsia is a pregnancy-specific disorder associated with pro-inflammatory and pro-thrombotic events. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Common genetic polymorphisms of GAS6 gene have previously been reported. The aim of this study was to investigate the association of GAS6 gene polymorphisms with the risk of preeclampsia in Chinese subjects. The case-control population consists of 551 subjects. The genotyping of the single-nucleotide polymorphisms of GAS6 gene, GAS6 834 +7G/A(rs8191974) and +1332C/T (rs1803628), was carried out on genomic DNA using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) analysis. There were significant differences in the +1332C/T genotype and allele frequencies between the patients with preeclampsia and the controls (P=0.03 and 0.02, respectively). The +1332 TT genotype was found to be protective from the development of preeclampsia (odds ratios 0.271, 95% confidence interval 0.077-0.953; P=0.03). Further analysis showed that the TT genotype of the GAS6 +1332C/T conferred a risk of severe preeclampsia (OR=0.597, 95% confidence interval 0.416-0.855; P=0.01). However, there were no differences in the 834+7G/A genotype and allele frequencies between the patients with preeclampsia and the controls. Our data suggest that a TT genotype at +1332C/T polymorphism might be associated with decreased risk for preeclampsia, but the 834+7G/A polymorphism is not associated with the disorder, in the Chinese population. Copyright © 2017. Published by Elsevier B.V.

  17. Marker-trait association analysis of frost tolerance of 672 worldwide pea (Pisum sativum L.) collections.

    PubMed

    Liu, Rong; Fang, Li; Yang, Tao; Zhang, Xiaoyan; Hu, Jinguo; Zhang, Hongyan; Han, Wenliang; Hua, Zeke; Hao, Junjie; Zong, Xuxiao

    2017-07-19

    Frost stress is one of the major abiotic stresses causing seedling death and yield reduction in winter pea. To improve the frost tolerance of pea, field evaluation of frost tolerance was conducted on 672 diverse pea accessions at three locations in Northern China in three growing seasons from 2013 to 2016 and marker-trait association analysis of frost tolerance were performed with 267 informative SSR markers in this study. Sixteen accessions were identified as the most winter-hardy for their ability to survive in all nine field experiments with a mean survival rate of 0.57, ranging from 0.41 to 0.75. Population structure analysis revealed a structured population of two sub-populations plus some admixtures in the 672 accessions. Association analysis detected seven markers that repeatedly had associations with frost tolerance in at least two different environments with two different statistical models. One of the markers is the functional marker EST1109 on LG VI which was predicted to co-localize with a gene involved in the metabolism of glycoproteins in response to chilling stress and may provide a novel mechanism of frost tolerance in pea. These winter-hardy germplasms and frost tolerance associated markers will play a vital role in marker-assisted breeding for winter-hardy pea cultivar.

  18. Extinction-effective population index: incorporating life-history variations in population viability analysis.

    PubMed

    Fujiwara, Masami

    2007-09-01

    Viability status of populations is a commonly used measure for decision-making in the management of populations. One of the challenges faced by managers is the need to consistently allocate management effort among populations. This allocation should in part be based on comparison of extinction risks among populations. Unfortunately, common criteria that use minimum viable population size or count-based population viability analysis (PVA) often do not provide results that are comparable among populations, primarily because they lack consistency in determining population size measures and threshold levels of population size (e.g., minimum viable population size and quasi-extinction threshold). Here I introduce a new index called the "extinction-effective population index," which accounts for differential effects of demographic stochasticity among organisms with different life-history strategies and among individuals in different life stages. This index is expected to become a new way of determining minimum viable population size criteria and also complement the count-based PVA. The index accounts for the difference in life-history strategies of organisms, which are modeled using matrix population models. The extinction-effective population index, sensitivity, and elasticity are demonstrated in three species of Pacific salmonids. The interpretation of the index is also provided by comparing them with existing demographic indices. Finally, a measure of life-history-specific effect of demographic stochasticity is derived.

  19. Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis.

    PubMed

    Zhang, Chang'e; Wang, Wenju; Zhang, Hong'e; Wei, Lulu; Guo, Shuping

    2016-06-28

    The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations.

  20. Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

    PubMed Central

    Wei, Lulu; Guo, Shuping

    2016-01-01

    Objectives The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. Methods A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. Results A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. Conclusions This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations. PMID:27270653

  1. Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

    PubMed

    Tang, Clara S; Zhang, He; Cheung, Chloe Y Y; Xu, Ming; Ho, Jenny C Y; Zhou, Wei; Cherny, Stacey S; Zhang, Yan; Holmen, Oddgeir; Au, Ka-Wing; Yu, Haiyi; Xu, Lin; Jia, Jia; Porsch, Robert M; Sun, Lijie; Xu, Weixian; Zheng, Huiping; Wong, Lai-Yung; Mu, Yiming; Dou, Jingtao; Fong, Carol H Y; Wang, Shuyu; Hong, Xueyu; Dong, Liguang; Liao, Yanhua; Wang, Jiansong; Lam, Levina S M; Su, Xi; Yan, Hua; Yang, Min-Lee; Chen, Jin; Siu, Chung-Wah; Xie, Gaoqiang; Woo, Yu-Cho; Wu, Yangfeng; Tan, Kathryn C B; Hveem, Kristian; Cheung, Bernard M Y; Zöllner, Sebastian; Xu, Aimin; Eugene Chen, Y; Jiang, Chao Qiang; Zhang, Youyi; Lam, Tai-Hing; Ganesh, Santhi K; Huo, Yong; Sham, Pak C; Lam, Karen S L; Willer, Cristen J; Tse, Hung-Fat; Gao, Wei

    2015-12-22

    Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

  2. Seasonal associations with urban light pollution for nocturnally migrating bird populations.

    PubMed

    La Sorte, Frank A; Fink, Daniel; Buler, Jeffrey J; Farnsworth, Andrew; Cabrera-Cruz, Sergio A

    2017-11-01

    The spatial extent and intensity of artificial light at night (ALAN) has increased worldwide through the growth of urban environments. There is evidence that nocturnally migrating birds are attracted to ALAN, and there is evidence that nocturnally migrating bird populations are more likely to occur in urban areas during migration, especially in the autumn. Here, we test if urban sources of ALAN are responsible, at least in part, for these observed urban associations. We use weekly estimates of diurnal occurrence and relative abundance for 40 nocturnally migrating bird species that breed in forested environments in North America to assess how associations with distance to urban areas and ALAN are defined across the annual cycle. Migratory bird populations presented stronger than expected associations with shorter distances to urban areas during migration, and stronger than expected association with higher levels of ALAN outside and especially within urban areas during migration. These patterns were more pronounced during autumn migration, especially within urban areas. Outside of the two migration periods, migratory bird populations presented stronger than expected associations with longer distances to urban areas, especially during the nonbreeding season, and weaker than expected associations with the highest levels of ALAN outside and especially within urban areas. These findings suggest that ALAN is associated with higher levels of diurnal abundance along the boundaries and within the interior of urban areas during migration, especially in the autumn when juveniles are undertaking their first migration journey. These findings support the conclusion that urban sources of ALAN can broadly effect migratory behavior, emphasizing the need to better understand the implications of ALAN for migratory bird populations. © 2017 John Wiley & Sons Ltd.

  3. A general methodology for population analysis

    NASA Astrophysics Data System (ADS)

    Lazov, Petar; Lazov, Igor

    2014-12-01

    For a given population with N - current and M - maximum number of entities, modeled by a Birth-Death Process (BDP) with size M+1, we introduce utilization parameter ρ, ratio of the primary birth and death rates in that BDP, which, physically, determines (equilibrium) macrostates of the population, and information parameter ν, which has an interpretation as population information stiffness. The BDP, modeling the population, is in the state n, n=0,1,…,M, if N=n. In presence of these two key metrics, applying continuity law, equilibrium balance equations concerning the probability distribution pn, n=0,1,…,M, of the quantity N, pn=Prob{N=n}, in equilibrium, and conservation law, and relying on the fundamental concepts population information and population entropy, we develop a general methodology for population analysis; thereto, by definition, population entropy is uncertainty, related to the population. In this approach, what is its essential contribution, the population information consists of three basic parts: elastic (Hooke's) or absorption/emission part, synchronization or inelastic part and null part; the first two parts, which determine uniquely the null part (the null part connects them), are the two basic components of the Information Spectrum of the population. Population entropy, as mean value of population information, follows this division of the information. A given population can function in information elastic, antielastic and inelastic regime. In an information linear population, the synchronization part of the information and entropy is absent. The population size, M+1, is the third key metric in this methodology. Namely, right supposing a population with infinite size, the most of the key quantities and results for populations with finite size, emerged in this methodology, vanish.

  4. Myocardial infarction among Danish HIV-infected individuals: population-attributable fractions associated with smoking.

    PubMed

    Rasmussen, Line D; Helleberg, Marie; May, Margaret T; Afzal, Shoaib; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Court; Gerstoft, Jan; Nordestgaard, Børge G; Obel, Niels

    2015-05-01

    Human immunodeficiency virus-infected individuals have increased risk of myocardial infarction (MI); however, the contribution from smoking and potentiating effects of HIV are controversial. From the Danish HIV Cohort Study and the Copenhagen General Population Study, we identified 3251 HIV-infected individuals and 13 004 population controls matched on age and gender. Data on MI were obtained from the National Hospital Registry and the National Registry of Causes of Death. We calculated adjusted incidence rate ratios (aIRR) for risk of MI and population-attributable fractions (PAF) of MI associated with smoking. In never smokers, HIV was not associated with an increased risk of MI (aIRR, 1.01; 95% confidence interval [CI], .41-2.54). In previous and current smokers, HIV was associated with a substantially increased risk of MI (aIRR, 1.78; 95% CI, .75-4.24 and aIRR, 2.83; 95% CI, 1.71-4.70). The PAF associated with ever smoking (previous or current) was 72% (95% CI, 55%-82%) for HIV-infected individuals and 24% (95% CI, 3%-40%) for population controls. If all current smokers stopped smoking, 42% (95% CI, 21%-57%) and 21% (95% CI, 12%-28%) of all MIs could potentially be avoided in these 2 populations. Smoking is associated with a higher risk of MI in the HIV-infected population than in the general population. Approximately 3 of 4 MIs among HIV-infected individuals are associated with ever smoking compared with only 1 of 4 MIs among population controls. Smoking cessation could potentially prevent more than 40% of MIs among HIV-infected individuals, and smoking cessation should be a primary focus in modern HIV care. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Population viability analysis of the Endangered shortnose sturgeon

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jager, Yetta; Bevelhimer, Mark S; Peterson, Douglas L.

    2011-07-01

    This study used population viability analysis (PVA) to partition the influences of potential threats to the endangered shortnose sturgeon (Acipenser brevirostrum). A workshop brought together experts to help identify potential threats including groundwater withdrawal, poor water quality, saltwater intrusion, mercury effects, harvest as by-catch, and sedimentation of spawning habitat. During the course of the project, we eliminated some threats and added new ones. Groundwater withdrawal was dismissed after a study failed to identify connection with groundwater and the majority of pumping is from a confined aquifer. We also eliminated activities on Fort Stewart as influences on spawning habitat because anymore » successful spawning must occur upstream of Fort Stewart. We added climate change to the list of threats based on our assessment of temperature effects and expectations of sea-level rise. Our study highlighted the role of populations in nearby rivers in providing metapopulation support, raising the concern that the population in the Ogeechee River acts as a demographic sink. As part of this study, we carried out a field sampling study to analyze effects of training activities on headwater streams. We developed a new methodology for sampling design as part of this effort and used a mixed-modeling approach to identify relationships between land cover-land use, including those associated with military training activity and water quality. We found that tank training was associated with higher suspended sediment and equipment training was associated with higher organic carbon) and water quality. We detected effects of training on suspended sediment and organic carbon. We also carried out a field sampling effort in the Canoochee and Ogeechee Rivers. In the Ogeechee River, we found that dissolved oxygen in 40% of measurements during summer were below 4 mg L-1. To evaluate mercury as a potential threat, we developed a mercury uptake model and analyzed mercury levels

  6. Mental Health Consequences of Childhood Physical Abuse in Chinese Populations: A Meta-Analysis.

    PubMed

    Ip, Patrick; Wong, Rosa S; Li, Sophia L; Chan, Ko Ling; Ho, Frederick K; Chow, Chun-Bong

    2016-12-01

    Childhood physical abuse (CPA) can lead to adverse mental health outcomes in adulthood, but its potential impact on Chinese populations is still unclear. This meta-analysis is the first to examine the association between CPA and mental health outcomes in Chinese populations. Studies published before December 31, 2014 were identified from Embase, CINAHL, Scopus, PsycINFO, PubMed, and Chinese National Knowledge Infrastructure databases. Studies with data on the association between CPA and mental health outcomes from Chinese subjects were included. Twenty-four studies were initially identified but two were excluded because of poor quality. Two reviewers independently extracted data to generate summary effect sizes using a random-effects meta-analytic model. A priori subgroup and sensitivity analyses were performed to evaluate heterogeneity and bias in these studies. Our meta-analysis of 22 studies found a significant positive association between CPA and overall mental health outcomes among all Chinese subjects (pooled effect size: odds ratio [OR] = 2.16, 95% confidence interval [CI] = [1.87, 2.49]) and among community samples (pooled effect size: OR = 2.06, 95% CI [1.71, 2.48]). Based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnostic criteria, CPA was more strongly associated with Axis II (OR = 2.62, 95% CI [2.13, 3.22]) than Axis I disorders (OR = 1.85, 95% CI [1.58, 2.17]). The detrimental effects of CPA on mental health outcomes in Chinese populations were comparable to, if not more than, the West. Contrary to the Chinese belief that physical punishment is a safe way to discipline children, our findings highlight the potential harm to mental health and the need to change this parenting practice. © The Author(s) 2015.

  7. Changes in size and trends of North American sea duck populations associated with North Pacific oceanic regime shifts

    USGS Publications Warehouse

    Flint, Paul L.

    2013-01-01

    Broad-scale multi-species declines in populations of North American sea ducks for unknown reasons is cause for management concern. Oceanic regime shifts have been associated with rapid changes in ecosystem structure of the North Pacific and Bering Sea. However, relatively little is known about potential effects of these changes in oceanic conditions on marine bird populations at broad scales. I examined changes in North American breeding populations of sea ducks from 1957 to 2011 in relation to potential oceanic regime shifts in the North Pacific in 1977, 1989, and 1998. There was strong support for population-level effects of regime shifts in 1977 and 1989, but little support for an effect of the 1998 shift. The continental-level effects of these regime shifts differed across species groups and time. Based on patterns of sea duck population dynamics associated with regime shifts, it is unclear if the mechanism of change relates to survival or reproduction. Results of this analysis support the hypothesis that population size and trends of North American sea ducks are strongly influenced by oceanic conditions. The perceived population declines appear to have halted >20 years ago, and populations have been relatively stable or increasing since that time. Given these results, we should reasonably expect dramatic changes in sea duck population status and trends with future oceanic regime shifts.

  8. Density-associated recruitment mediates coral population dynamics on a coral reef

    NASA Astrophysics Data System (ADS)

    Bramanti, Lorenzo; Edmunds, Peter J.

    2016-06-01

    Theory suggests that density-associated processes can modulate community resilience following declines in population size. Here, we demonstrate density-associated processes in two scleractinian populations on the outer reef of Moorea, French Polynesia, that are rapidly increasing in size following the effects of two catastrophic disturbances. Between 2006 and 2010, predation by the corallivorous crown-of-thorns sea star reduced coral cover by 93 %; in 2010, the dead coral skeletons were removed by a cyclone, and in 2011 and 2012, high coral recruitment initiated population recovery. Coral recruitment was associated with coral cover, but the relationship differed between two coral genera that are almost exclusively broadcast spawners in Moorea. Acroporids recruited at low densities, and the density of recruits was positively associated with cover of Acropora, whereas pocilloporids recruited at high densities, and densities of their recruits were negatively associated with cover of Pocillopora. Together, our results suggest that associations between adult cover and density of both juveniles and recruits can mediate rapid coral community recovery after large disturbances. The difference between taxa in sign of the relationships between recruit density and coral cover indicate that they reflect contrasting mechanisms with the potential to mediate temporal shifts in taxonomic composition of coral communities.

  9. Association of reading disability on chromosome 6p22 in the Afrikaner population.

    PubMed

    Platko, Jill V; Wood, Frank B; Pelser, Izelda; Meyer, Marianne; Gericke, George S; O'Rourke, Julia; Birns, Julie; Purcell, Shaun; Pauls, David L

    2008-10-05

    The genetic basis of reading disability (RD) has long been established through family and twin studies. More recently genetic linkage studies have identified genomic regions that appear to harbor susceptibility genes for RD. Association studies have been shown to have greater power for detecting genes of modest effect, particularly in genetically isolated populations. Hence, a case control study of RD was undertaken in the Afrikaner population in South Africa. Sixty-eight microsatellite markers in regions where linkages had been reported in previous studies were genotyped on 122 children with reading disability and 112 typically reading controls drawn from the same school population. A single allele of marker D6S299 showed a highly significant association with the RD phenotype (D6S299[229], P-value 0.000014). Other markers on other chromosomes also showed suggestive associations. Of particular interest were markers on chromosomes 1 and 15. These two regions have been implicated in studies of populations that formed the founding population in the Afrikaner population.

  10. Population pharmacokinetic (PK) analysis of laromustine, an emerging alkylating agent, in cancer patients.

    PubMed

    Nassar, Ala F; Wisnewski, Adam V; King, Ivan

    2017-05-01

    1. Alkylating agents are capable of introducing an alkyl group into nucleophilic sites on DNA or RNA through covalent bond. Laromustine is an active member of a relatively new class of sulfonylhydrazine prodrugs under development as antineoplastic alkylating agents, and displays significant single-agent activity. 2. This is the first report of the population pharmacokinetic analysis of laromustine, 106 patients, 66 with hematologic malignancies and 40 with solid tumors, participated in five clinical trials worldwide. Of these, 104 patients were included in the final NONMEM analysis. 3. The population estimates for total clearance (CL) and volume of distribution of the central compartment (V 1 ) were 96.3 L/h and 45.9 L, associated with high inter-patient variability of 52.9% and 79.8% and inter-occasion variability of 26.7% and 49.3%, respectively. The population estimates for Q and V 2 were 73.2 L/h and 29.9 L, and inter-patient variability in V 2 was 63.1%, respectively. 4. The estimate of V ss (75.8 L) exceeds total body water, indicating that laromustine is distributed to tissues. The half-life is short, less than 1 h, reflecting rapid clearance. Population PK analysis showed laromustine pharmacokinetics to be independent of dose and organ function with no effect on subsequent dosing cycles.

  11. Paranoid Ideation and Violence: Meta-analysis of Individual Subject Data of 7 Population Surveys

    PubMed Central

    Coid, Jeremy W.; Ullrich, Simone; Bebbington, Paul; Fazel, Seena; Keers, Robert

    2016-01-01

    There is controversy whether associations between psychosis and violence are due to coexisting substance misuse and factors increasing risk in nonpsychotic persons. Recent studies in clinical samples have implicated independent effects of paranoid delusions. Research findings suggest that individual psychotic-like-experiences on the psychosis continuum in the general population are associated with violence; it remains unclear whether this association is due to psychiatric comorbidity. We pooled data from 7 UK general population surveys (n = 23 444) and conducted a meta-analysis of individual subject data. Further meta-analyses were performed to identify heterogeneity. Main exposure variables: 5 psychotic-like-experiences and a categorical measure of psychosis. Comorbidity was established through standardized self-report instruments. Information was collected on violence, severity, victims. Paranoid ideation was associated with violence (AOR 2.26, 95% CI 1.75–2.91), severity and frequency, even when controlling for effects of other psychotic-like-experiences. Associations were not explained by comorbid conditions, including substance dependence. Psychotic disorder was associated with violence and injury to the perpetrator but associations were explained by paranoid ideation. Individual associations between hypomania, thought insertion, hallucinations, and violence were nonsignificant after adjustments, and significantly associated only when comorbid with antisocial personality disorder. Strange experiences were only associated with intimate partner violence. Paranoid ideation on a psychosis-continuum in the general population was associated with violence. All other associations were explained by comorbidity. Further investigation should determine whether paranoid ideation among persons in the community require preventive interventions, similar to those presenting to mental health services. Nevertheless, risks are considerably increased for psychotic

  12. Exome-wide Association Study Identifies CLEC3B Missense Variant p.S106G as Being Associated With Extreme Longevity in East Asian Populations

    PubMed Central

    Tanisawa, Kumpei; Arai, Yasumichi; Hirose, Nobuyoshi; Shimokata, Hiroshi; Yamada, Yoshiji; Kawai, Hisashi; Kojima, Motonaga; Obuchi, Shuichi; Hirano, Hirohiko; Yoshida, Hideyo; Suzuki, Hiroyuki; Fujiwara, Yoshinori; Ihara, Kazushige; Sugaya, Maki; Arai, Tomio; Mori, Seijiro; Sawabe, Motoji; Sato, Noriko; Muramatsu, Masaaki; Higuchi, Mitsuru; Liu, Yao-Wen; Kong, Qing-Peng

    2017-01-01

    Abstract Life span is a complex trait regulated by multiple genetic and environmental factors; however, the genetic determinants of extreme longevity have been largely unknown. To identify the functional coding variants associated with extreme longevity, we performed an exome-wide association study (EWAS) on a Japanese population by using an Illumina HumanExome Beadchip and a focused replication study on a Chinese population. The EWAS on two independent Japanese cohorts consisting of 530 nonagenarians/centenarians demonstrated that the G allele of CLEC3B missense variant p.S106G was associated with extreme longevity at the exome-wide level of significance (p = 2.33×10–7, odds ratio [OR] = 1.50). The CLEC3B gene encodes tetranectin, a protein implicated in the mineralization process in osteogenesis as well as in the prognosis and metastasis of cancer. The replication study consisting of 448 Chinese nonagenarians/centenarians showed that the G allele of CLEC3B p.S106G was also associated with extreme longevity (p = .027, OR = 1.51), and the p value of this variant reached 1.87×10–8 in the meta-analysis of Japanese and Chinese populations. In conclusion, the present study identified the CLEC3B p.S106G as a novel longevity-associated variant, raising the novel hypothesis that tetranectin, encoded by CLEC3B, plays a role in human longevity and aging. PMID:27154906

  13. Association of five SNPs with human hair colour in the Polish population.

    PubMed

    Siewierska-Górska, A; Sitek, A; Żądzińska, E; Bartosz, G; Strapagiel, D

    2017-03-01

    Twenty-two variants (single nucleotide polymorphisms - SNPs) of the genes involved in hair pigmentation (OCA2, HERC2, MC1R, SLC24A5, SLC45A2, TPCN2, TYR, TYRP1) were genotyped in a group of 186 Polish participants, representing a range of hair colours (45 red, 64 blond, 77 dark). A genotype-phenotype association analysis was performed. Using z-statistics we identified three variants highly associated with different hair colour categories (rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R). Two variants: rs1800401:C>T in OCA2 and rs16891982:C>G in SLC45A2 showed a high probability of a relation with hair colour, although that probability did not exceed the threshold of statistical significance after applying the Bonferroni correction. We created and validated mathematical logistic regression models in order to test the usefulness of the sets of polymorphisms for hair colour prediction in the Polish population. We subjected four models to stratified cross-validation. The first model consisted of three polymorphisms that proved to be important in the associative analysis. The second model included, apart from the mentioned polymorphisms, additionally rs16891982:C>G in SLC45A. The third model included, apart from the variants relevant in the associating analysis, rs1800401:C>T in OCA. The fourth model consisted of the set of polymorphisms from the first model supplemented with rs16891982:C>G in SLC45A and rs1800401:C>T in OCA. The validation of our models has shown that the inclusion of rs16891982:C>G in SLC45A and rs1800401:C>T in OCA increases the prediction of red hair in comparison with the algorithm including only rs12913832:A>G in HERC2, rs1805007:T>C and rs1805008:C>T in MC1R. The model consisting of all the five above-mentioned genetic variants has shown good prediction accuracies, expressed by the area under the curve (AUC) of the receiver operating characteristics: 0.84 for the red-haired, 0.82 for the dark-haired and 0.71 for the blond

  14. Bacterial Populations Associated with Smokeless Tobacco Products

    PubMed Central

    Han, Jing; Sanad, Yasser M.; Deck, Joanna; Sutherland, John B.; Li, Zhong; Walters, Matthew J.; Duran, Norma; Holman, Matthew R.

    2016-01-01

    ABSTRACT There are an estimated 8 million users of smokeless tobacco products (STPs) in the United States, and yet limited data on microbial populations within these products exist. To better understand the potential microbiological risks associated with STP use, a study was conducted to provide a baseline microbiological profile of STPs. A total of 90 samples, representing 15 common STPs, were purchased in metropolitan areas in Little Rock, AR, and Washington, DC, in November 2012, March 2013, and July 2013. Bacterial populations were evaluated using culture, pyrosequencing, and denaturing gradient gel electrophoresis (DGGE). Moist-snuff products exhibited higher levels of bacteria (average of 1.05 × 106 CFU/g STP) and diversity of bacterial populations than snus (average of 8.33 × 101 CFU/g STP) and some chewing tobacco products (average of 2.54 × 105 CFU/g STP). The most common species identified by culturing were Bacillus pumilus, B. licheniformis, B. safensis, and B. subtilis, followed by members of the genera Oceanobacillus, Staphylococcus, and Tetragenococcus. Pyrosequencing analyses of the 16S rRNA genes identified the genera Tetragenococcus, Carnobacterium, Lactobacillus, Geobacillus, Bacillus, and Staphylococcus as the predominant taxa. Several species identified are of possible concern due to their potential to cause opportunistic infections and reported abilities to reduce nitrates to nitrites, which may be an important step in the formation of carcinogenic tobacco-specific N′-nitrosamines. This report provides a microbiological baseline to help fill knowledge gaps associated with microbiological risks of STPs and to inform potential regulations regarding manufacture and testing of STPs. IMPORTANCE It is estimated that there 8 million users of smokeless tobacco products (STPs) in the United States; however, there are limited data on microbial populations that exist within these products. The current study was undertaken to better understand the

  15. ZNF208 polymorphisms associated with ischemic stroke in a southern Chinese Han population.

    PubMed

    Yu, Jianzhong; Zhou, Feng; Luo, Dong; Wang, Nianzhen; Zhang, Chong; Jin, Tianbo; Liang, Xiongfei; Yu, Dan

    2017-01-01

    Ischemic stroke is one of the most common diseases with a high burden of neurological deficits, disability and death. Zinc finger protein 208 (ZNF208) was found to be involved in coronary heart disease, although little information is available about its association with ischemic stroke. We performed the present case-control study to clarify the association between single-nucleotide polymorphisms (SNPs) within ZNF208 and the risk of ischemic stroke in a southern Chinese Han population. A total of 799 subjects (400 cases and 399 healthy controls) were enrolled in the present study. Five SNPs within ZNF208 gene were selected and genotyped using Sequenom MassARRY technology (Sequenom, Inc., San Diego, CA, USA). Data management and statistical analyses were conducted using Sequenom Typer, version 4.0, and a chi-squared test, as well as unconditional logistic regression. Statistical results showed that three variants were associated with the risk of ischemic stroke under allele models (rs2188971, rs2188972, rs8103163 and rs7248488). The variant rs2188972 was also associated with the risk of ischemic stroke in a recessive model after adjustment for age and sex. Haplotype analysis suggested that a significant difference existed between the A rs2188972 T rs2188971 A rs8103163 A rs7248488 haplotype and the risk of ischemic stroke, although this disappeared after adjustment for sex and age. The results obtained in the present study indicate a potential association between ZNF208 variants and the risk of ischemic risk in a southern Chinese Han population. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Population trends in northern spotted owls: Associations with climate in the Pacific Northwest

    USGS Publications Warehouse

    Glenn, E.M.; Anthony, R.G.; Forsman, E.D.

    2010-01-01

    We used reverse time capture-mark-recapture models to describe associations between rate of population change (??) and climate for northern spotted owls (Strix occidentalis caurina) at six long-term study areas in Washington and Oregon, USA. Populations in three of six areas showed strong evidence of declining populations, while populations in two additional areas were likely declining as well. At four areas, ?? was positively associated with wetter-than-normal conditions during the growing season, which likely affects prey availability. Lambda was also negatively associated with cold, wet winters and nesting seasons, and the number of hot summer days. The amount of annual variation in ?? accounted for by climate varied across study areas (3-85%). Rate of population change was more sensitive to adult survival than to recruitment; however, there was considerable variation among years and across study areas for all demographic rates. While annual survival was more closely related to regional climate conditions, recruitment was often associated with local weather. In addition to climate, declines in recruitment at four of six areas were associated with increased presence of barred owls. Climate change models predict warmer, wetter winters and hotter, drier summers for the Pacific Northwest in the first half of the 21st century. Our results indicate that these conditions have the potential to negatively affect annual survival, recruitment, and consequently population growth rates for northern spotted owls. ?? 2010 Elsevier Ltd.

  17. Associations between bone mineral density and subclinical atherosclerosis: a cross-sectional study of a Chinese population.

    PubMed

    Liang, Dong-Ke; Bai, Xiao-Juan; Wu, Bing; Han, Lu-Lu; Wang, Xiao-Nan; Yang, Jun; Chen, Xiang-Mei

    2014-02-01

    The significance of associations between bone mineral density (BMD) and atherosclerosis in the Asian population is less clear. The aim of this study was to explore the population-level associations between BMD and subclinical atherosclerosis. This was a community-based cross-sectional study conducted in Shenyang, China. A total of 385 Chinese women and men aged 37-87 years were studied. The BMD was measured at the total hip and lumbar spine using dual-energy x-ray absorptiometry. The ankle-brachial index (ABI), pulse wave velocity (PWV), and carotid intima-media thickness (CIMT) were measured to assess atherosclerosis. Multiple regression analysis was applied to study the associations. Multicolinearity was examined using the variance inflation factor, condition index, and variance proportions. Factor analysis and principal component regression were used to remove the problem of multicolinearity. The differences of ABI, PWV, and CIMT among the normal BMD, osteopenia, and osteoporosis groups were not found. Total hip BMD was correlated with ABI in women after adjustment for age (r = 0.156). Sex-specific regression models included adjustment for age, body mass index, cigarette smoking, alcohol consumption, menopausal status (women), systolic blood pressure, diastolic blood pressure, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, serum uric acid, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and fibrinogen. Total hip BMD was associated with ABI in women after adjustment for age (per SD decrease in ABI: -0.130 g/cm(2), P = .022), but the association was borderline significant after full adjustment (P = .045). Total hip BMD and lumbar spine BMD were not associated with ABI, PWV, and CIMT after full adjustment in participants without a fracture history. The risk of osteoporosis was not associated with ABI, PWV, and CIMT. Low BMD is not associated with

  18. Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population.

    PubMed

    Liu, Xiaoxi; Kawamura, Yoshiya; Shimada, Takafumi; Otowa, Takeshi; Koishi, Shinko; Sugiyama, Toshiro; Nishida, Hisami; Hashimoto, Ohiko; Nakagami, Ryoichi; Tochigi, Mamoru; Umekage, Tadashi; Kano, Yukiko; Miyagawa, Taku; Kato, Nobumasa; Tokunaga, Katsushi; Sasaki, Tsukasa

    2010-03-01

    The oxytocin receptor (OXTR) gene, which is located on chromosome 3p25.3, has been implicated as a candidate gene for susceptibility of autism spectrum disorder (ASD). Positive associations between OXTR and ASD have been reported in earlier studies. However, the results were inconsistent and demand further studies. In this study, we investigated the associations between OXTR and ASD in a Japanese population by analyzing 11 single-nucleotide polymorphisms (SNPs) using both family-based association test (FBAT) and population-based case-control test. No significant signal was detected in the FBAT test. However, significant differences were observed in allelic frequencies of four SNPs, including rs2254298 between patients and controls. The risk allele of rs2254298 was 'A', which was consistent with the previous study in Chinese, and not with the observations in Caucasian. The difference in the risk allele of this SNP in previous studies might be attributable to an ethnic difference in the linkage disequilibrium structure between the Asians and Caucasians. In addition, haplotype analysis exhibits a significant association between a five-SNP haplotype and ASD, including rs22542898. In conclusion, our study might support that OXTR has a significant role in conferring the risk of ASD in the Japanese population.

  19. Association of ACE Gene I/D polymorphism with migraine in Kashmiri population.

    PubMed

    Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

    2016-01-01

    Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine.

  20. Retracted: Association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in a Caucasian population.

    PubMed

    Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen

    2015-03-01

    The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with type-2 diabetic nephropathy (T2DN) susceptibility and the risk of type-2 diabetes mellitus (T2DM) developing into T2DN in Caucasian populations is still controversial. A meta-analysis was performed to evaluate the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Sixteen articles were identified for the analysis of the association of ACE I/D gene polymorphism with T2DN susceptibility and the risk of T2DM developing into T2DN in Caucasian populations. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. Sensitivity analysis according to sample size of case (<100 vs. ≥100) was also performed, and the results were similar to the non-sensitivity analysis. ACE I/D gene polymorphism was not associated with T2DN susceptibility and the risk of patients with T2DM developing T2DN in Caucasian populations. However, more studies should be performed in the future. © The Author(s) 2014.

  1. Genomic Approach to Understand the Association of DNA Repair with Longevity and Healthy Aging Using Genomic Databases of Oldest-Old Population

    PubMed Central

    Kim, Hyun Soo

    2018-01-01

    Aged population is increasing worldwide due to the aging process that is inevitable. Accordingly, longevity and healthy aging have been spotlighted to promote social contribution of aged population. Many studies in the past few decades have reported the process of aging and longevity, emphasizing the importance of maintaining genomic stability in exceptionally long-lived population. Underlying reason of longevity remains unclear due to its complexity involving multiple factors. With advances in sequencing technology and human genome-associated approaches, studies based on population-based genomic studies are increasing. In this review, we summarize recent longevity and healthy aging studies of human population focusing on DNA repair as a major factor in maintaining genome integrity. To keep pace with recent growth in genomic research, aging- and longevity-associated genomic databases are also briefly introduced. To suggest novel approaches to investigate longevity-associated genetic variants related to DNA repair using genomic databases, gene set analysis was conducted, focusing on DNA repair- and longevity-associated genes. Their biological networks were additionally analyzed to grasp major factors containing genetic variants of human longevity and healthy aging in DNA repair mechanisms. In summary, this review emphasizes DNA repair activity in human longevity and suggests approach to conduct DNA repair-associated genomic study on human healthy aging.

  2. Evolutionary consequences of microhabitat: population-genetic structuring in kelp- vs. rock-associated chitons.

    PubMed

    Nikula, R; Spencer, H G; Waters, J M

    2011-12-01

    Rafting has long been invoked as a key marine dispersal mechanism, but biologists have thus far produced little genetic evidence to support this hypothesis. We hypothesize that coastal species associated with buoyant seaweeds should experience enhanced population connectivity owing to rafting. In particular, invertebrates strongly associated with the buoyant bull-kelp Durvillaea antarctica might be expected to have lower levels of population-genetic differentiation than taxa mainly exploiting nonbuoyant substrates. We undertook a comparative genetic study of two codistributed, congeneric chiton species, assessing population connectivity at scales of 61-516 km, using ≥ 186 polymorphic AFLP loci per species. Consistent with predictions, population-genetic differentiation was weaker in the kelp-associated Sypharochiton sinclairi than in the rock-associated S. pelliserpentis. Additionally, while we found a significant positive correlation between genetic and oceanographic distances in both chiton species, the correlation was stronger in S. pelliserpentis (R(2) = 0.28) than in S. sinclairi (R(2) = 0.18). These data support the hypothesis that epifaunal taxa can experience enhanced population-genetic connectivity as a result of their rafting ability. © 2011 Blackwell Publishing Ltd.

  3. Prevalence of peripheral artery disease (PAD) and factors associated: An epidemiological analysis from the population-based Screening PRE-diabetes and type 2 DIAbetes (SPREDIA-2) study.

    PubMed

    Cornejo Del Río, V; Mostaza, J; Lahoz, C; Sánchez-Arroyo, V; Sabín, C; López, S; Patrón, P; Fernández-García, P; Fernández-Puntero, B; Vicent, D; Montesano-Sánchez, L; García-Iglesias, F; González-Alegre, T; Estirado, E; Laguna, F; de Burgos-Lunar, C; Gómez-Campelo, P; Abanades-Herranz, J C; de Miguel-Yanes, J M; Salinero-Fort, M A

    2017-01-01

    To describe the prevalence of Peripheral Artery Disease (PAD) in a random population sample and to evaluate its relationship with Mediterranean diet and with other potential cardiovascular risk factors such as serum uric acid and pulse pressure in individuals ranged 45 to 74 years. Cross-sectional analysis of 1568 subjects (mean age 6.5 years, 43% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and HbA1C levels. An oral glucose tolerance test was performed in non-diabetic subjects. PAD was evaluated by ankle-brachial index and/or having a prior diagnosis. PAD prevalence was 3.81% (95% CI, 2.97-4.87) for all participants. In men, PAD prevalence was significantly higher than in women [5.17% (95% CI, 3.74-7.11) vs. 2.78% (95% CI, 1.89-4.07); p = 0.014]. Serum uric acid in the upper quartile was associated with the highest odds ratio (OR) of PAD (for uric acid > 6.1 mg/dl, OR = 4.31; 95% CI, 1.49-12.44). The remaining variables more strongly associated with PAD were: Heart rate >90 bpm (OR = 4.16; 95%CI, 1.62-10.65), pulse pressure in the upper quartile (≥ 54 mmHg) (OR = 3.82; 95%CI, 1.50-9.71), adherence to Mediterranean diet (OR = 2.73; 95% CI, 1.48-5.04), and former smoker status (OR = 2.04; 95%CI, 1.00-4.16). Our results show the existence of a low prevalence of peripheral artery disease in a population aged 45-74 years. Serum uric acid, pulse pressure and heart rate >90 bpm were strongly associated with peripheral artery disease. The direct association between Mediterranean diet and peripheral artery disease that we have found should be evaluated through a follow-up study under clinical practice conditions.

  4. Association of LMX1A genetic polymorphisms with susceptibility to congenital scoliosis in Chinese Han population.

    PubMed

    Wu, Nan; Yuan, Suomao; Liu, Jiaqi; Chen, Jun; Fei, Qi; Liu, Sen; Su, Xinlin; Wang, Shengru; Zhang, Jianguo; Li, Shugang; Wang, Yipeng; Qiu, Guixing; Wu, Zhihong

    2014-10-01

    A genetic association study of single nucleotide polymorphisms (SNPs) for the LMX1A gene with congenital scoliosis (CS) in the Chinese Han population. To determine whether LMX1A genetic polymorphisms are associated with susceptibility to CS. CS is a lateral curvature of the spine due to congenital vertebral defects, whose exact genetic cause has not been well established. The LMX1A gene was suggested as a potential human candidate gene for CS. However, no genetic study of LMX1A in CS has ever been reported. We genotyped 13 SNPs of the LMX1A gene in 154 patients with CS and 144 controls with matched sex and age. After conducting the Hardy-Weinberg equilibrium test, the data of 13 SNPs were analyzed by the allelic and genotypic association with logistic regression analysis. Furthermore, the genotype-phenotype association and haplotype association analysis were also performed. The 13 SNPs of the LMX1A gene met Hardy-Weinberg equilibrium in the controls, which was not in the cases. None of the allelic and genotypic frequencies of these SNPs showed significant difference between case and control groups (P > 0.05). However, the genotypic frequencies of rs1354510 and rs16841013 in the LMX1A gene were associated with CS predisposition in the unconditional logistic regression analysis (P = 0.02 and 0.018, respectively). Genotypic frequencies of 3 SNPs at rs6671290, rs1354510, and rs16841013 were found to exhibit significant differences between patients with CS with failure of formation and the healthy controls (P = 0.019, 0.007, and 0.006, respectively). Besides, in the model analysis by using unconditional logistic regression analysis, the optimized model for the 3 genotypic positive SNPs with failure of formation were rs6671290 (codominant; P = 0.025, Akaike information value = 316.6, Bayesian information criterion = 333.9), rs1354510 (overdominant; P = 0.0017, Akaike information value = 312.1, Bayesian information criterion = 325.9), and rsl6841013 (overdominant; P = 0

  5. The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population.

    PubMed

    Chen, Xiaohua; Du, Hua; Liu, Binjian; Zou, Li; Chen, Wei; Yang, Yang; Zhu, Ying; Gong, Yajie; Tian, Jianbo; Li, Feng; Zhong, Shan

    2015-01-01

    Aberrant alternative splicing included alterations in components of the mRNA splicing machinery often occurred in colon cancer. However, the role of SF3A1, one key component of the mRNA splicing machinery, on colorectal cancer (CRC) risk was still not elucidated. We performed a hospital-based case-control study containing 801 CRC patients and 817 cancer-free controls to examine the association between SF3A1 polymorphisms and CRC risk in a Chinese population. Four candidate SNPs (rs10376, rs5753073, rs2839998 and rs2074733) were selected based on bioinformatics analysis and previous findings. The results showed no significant associations between these SNPs and CRC risk (P > 0.05). Besides, the stratified analysis based on the smoking and alcohol use status obtained no statistically significant results. Our study was the first one to investigate the association between SF3A1 polymorphisms and CRC risk. The results suggested these four SNPs in SF3A1 were not associated with CRC risk in a Chinese population, however, further more studies are needed to confirm our findings.

  6. Correction of Population Stratification in Large Multi-Ethnic Association Studies

    PubMed Central

    Serre, David; Montpetit, Alexandre; Paré, Guillaume; Engert, James C.; Yusuf, Salim; Keavney, Bernard; Hudson, Thomas J.; Anand, Sonia

    2008-01-01

    Background The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification. Methodology/Principal Findings We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification. Conclusions/Significance Our results highlight the importance of carefully addressing population stratification and of carefully “cleaning” the sample prior to analyses to obtain stronger signals of association and to avoid spurious results. PMID:18196181

  7. Declining scaup populations: A retrospective analysis of long-term population and harvest survey data

    USGS Publications Warehouse

    Afton, A.D.; Anderson, M.G.

    2001-01-01

    We examined long-term databases concerning population status of scaup (lesser [Aythya affinis] and greater scaup [A. marila] combined) and harvest statistics of lesser scaup to identify factors potentially limiting population growth. Specifically, we explored evidence for and against the general hypotheses that scaup populations have declined in association with declining recruitment and/or female survival. We examined geographic heterogeneity in scaup demographic patterns that could yield evidence about potential limiting factors. Several biases exist in survey methodology used to estimate scaup populations and harvest statistics; however, none of these biases likely accounted for our major findings that (1) the continental scaup breeding population has declined over the last 20 years, with widespread and consistent declines within surveyed areas of the Canadian western boreal forest where most lesser scaup breed; (2) sex ratios of lesser scaup in the U.S. harvest have increased (more males now relative to females); and (3) age ratios of lesser scaup in the U.S. harvest have declined (fewer immatures now relative to adults), especially in the midcontinent region. We interpreted these major findings as evidence that (1) recruitment of lesser scaup has declined over the last 20 years, particularly in the Canadian western boreal forest; and (2) survival of female lesser scaup has declined relative to that of males. We found little evidence that harvest was associated with the scaup population decline. Our findings underscore the need for both improvements and changes to population survey procedures and new research to discriminate among various hypotheses explaining the recent scaup population decline.

  8. Genome-Wide Association Study of Breast Cancer in the Japanese Population

    PubMed Central

    Low, Siew-Kee; Takahashi, Atsushi; Ashikawa, Kyota; Inazawa, Johji; Miki, Yoshio; Kubo, Michiaki; Nakamura, Yusuke; Katagiri, Toyomasa

    2013-01-01

    Breast cancer is the most common malignancy among women in worldwide including Japan. Several studies have identified common genetic variants to be associated with the risk of breast cancer. Due to the complex linkage disequilibrium structure and various environmental exposures in different populations, it is essential to identify variants associated with breast cancer in each population, which subsequently facilitate the better understanding of mammary carcinogenesis. In this study, we conducted a genome-wide association study (GWAS) as well as whole-genome imputation with 2,642 cases and 2,099 unaffected female controls. We further examined 13 suggestive loci (P<1.0×10−5) using an independent sample set of 2,885 cases and 3,395 controls and successfully validated two previously-reported loci, rs2981578 (combined P-value of 1.31×10−12, OR = 1.23; 95% CI = 1.16–.30) on chromosome 10q26 (FGFR2), rs3803662 (combined P-value of 2.79×10−11, OR = 1.21; 95% CI = 1.15–.28) and rs12922061 (combined P-value of 3.97×10−10, OR = 1.23; 95% CI = 1.15–.31) on chromosome 16q12 (TOX3-LOC643714). Weighted genetic risk score on the basis of three significantly associated variants and two previously reported breast cancer associated loci in East Asian population revealed that individuals who carry the most risk alleles in category 5 have 2.2 times higher risk of developing breast cancer in the Japanese population than those who carry the least risk alleles in reference category 1. Although we could not identify additional loci associated with breast cancer, our study utilized one of the largest sample sizes reported to date, and provided genetic status that represent the Japanese population. Further local and international collaborative study is essential to identify additional genetic variants that could lead to a better, accurate prediction for breast cancer. PMID:24143190

  9. The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

    PubMed Central

    Oh, Il Hwan; Park, Jung Hwan; Lee, Chang Hwa; Park, Joon-Sung

    2015-01-01

    Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV1, 93.8 ± 0.5% pred, P < 0.0001) and FEV1/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV1 (β = -5.591589, P < 0.0001), but not to FEV1/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV1/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV1 and may be a reliable predictor of poor lung function, especially the restrictive pattern. PMID:25658743

  10. Place matters: A longitudinal analysis measuring the association between neighbourhood walkability and walking by age group and population center size in Canada.

    PubMed

    Wasfi, Rania; Steinmetz-Wood, Madeleine; Kestens, Yan

    2017-01-01

    This study examined the influence of walkability on walking behaviour and assessed whether associations varied according to life-stage and population center (PC) size. Walkability scores were obtained for the six-digit postal codes of residential neighbourhoods of 11,200 Canadians, who participated in biennial assessments of the National Population Health Survey from 1994 to 2010. Participants were stratified by age-group. Mixed-effects logistic regression models were used to estimate the influence of cumulative exposure to neighborhood walkability on utilitarian and exercise walking by PC size and life-stage. Associations of neighbourhood walkability with utilitarian and exercise walking varied according to age-group and PC size. Exposure to high walkable neighborhoods was associated with utilitarian walking in younger and older adults in all PC sizes, except for older adults living in a medium PC. Living in a highly walkable neighborhood in a large PC was associated with walking for exercise in younger (OR: 1.42; 95%CI: 1.20-1.67) and older adults (OR: 2.09; 95%CI: 1.51-2.89). Living in highly walkable neighbourhood in a medium PC was associated with walking for exercise in older adults (OR: 1.62; 95%CI: 1.15-2.29). These results emphasize the need to consider the size and nature of every community, and the age-group of a population when implementing strategies to promote walking.

  11. Genetic association of APOB polymorphisms with variation in serum lipid profile among the Kuwait population.

    PubMed

    Al-Bustan, Suzanne A; Alnaqeeb, Majed A; Annice, Babitha G; Ebrahim, Ghada A; Refai, Thanaa M

    2014-10-08

    Several studies have identified APOB as a candidate gene predisposing individuals to dyslipidemia. Polymorphisms including the signal peptide (rs11279109), codon 2488 XbaI (rs1042031), codon 3611 MspI (rs693), codon 4154 EcoRI (rs1801701) and the 3' variable number of tandem repeats have been reported to be associated with dyslipidemia in several populations. With limited studies on Arabs, this study aimed to investigate the genetic association of APOB polymorphisms and assess the potential influence of minor and rare alleles on serum lipid levels in the Kuwaiti population. A total of 795 Kuwaiti subjects, documented with phenotypic data and fasting serum lipid levels, were genotyped for the five polymorphisms using PCR, PCR-RFLP and gene fragment analysis. Genotype and allele association with variation in serum lipid levels as well as haplotypes were analyzed using chi-square test, univariate and logistic regression analysis. Analysis of the genotype and allele frequencies distribution revealed a significant positive association between the APOB signal peptide and 3611 MspI polymorphisms with increased levels of triglycerides (statistical power of 80%). Haplotype analysis further supported the findings by showing that carriers of haplotypes (IX-M-E+M) had significantly lower mean (SD) TG levels (0.86 ± 0.07) as compared to non-carriers (1.01 ± 0.02). Significance was also observed with regards to positive family history of hypercholesterolemia. The results imply a "protective role" for two alleles (rs11279109 and rs1801701) in which logistic regression analysis showed a significant half-fold decrease in the risk for heterozygotes of rs11279109 and an 8.8 fold decrease in the risk for homozygous M-M- of rs1801701 of having lower TG levels (<1.70 mmol/L) in individuals. This suggests that genetic interaction between various polymorphisms at different gene loci act in linkage disequilibrium to affect serum TG levels. Apo B genotyping may be a useful adjunct

  12. PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population.

    PubMed

    Aslibekyan, Stella; Dashti, Hassan S; Tanaka, Toshiko; Sha, Jin; Ferrucci, Luigi; Zhi, Degui; Bandinelli, Stefania; Borecki, Ingrid B; Absher, Devin M; Arnett, Donna K; Ordovas, Jose M

    2014-11-01

    Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n=991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461,281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p=9.2×10(-8)), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p=1.5×10(-10)) and rs4405858 (p=1.9×10(-9)). These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism.

  13. KIR Genotypic Diversity Can Track Ancestries in Heterogeneous Populations: A Potential Confounder for Disease Association Studies

    PubMed Central

    Singh, Komal Manpreet; Phung, Yume T.; Kohla, Mohamed S.; Lan, Billy Y-A; Chan, Sharon; Suen, Diana L.; Murad, Sahar; Rheault, Shana; Davidson, Peter; Evans, Jennifer; Singh, Manpreet; Dohil, Sofie; Osorio, Robert W.; Wakil, Adil E.; Page, Kimberly; Feng, Sandy; Cooper, Stewart L.

    2014-01-01

    Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets, and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by selfassigned ethnicities, and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC); 17 in 47 African Americans (NCAA); 21 in 80 Asians (NCA); 20 in 74 Hispanics (NCH) and 18 in 54 “other” ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR based studies to avert spurious associations. PMID:21898189

  14. Association of methionine synthase gene polymorphisms with wool production and quality traits in Chinese Merino population.

    PubMed

    Rong, E G; Yang, H; Zhang, Z W; Wang, Z P; Yan, X H; Li, H; Wang, N

    2015-10-01

    Methionine synthase (MTR) plays a crucial role in maintaining homeostasis of intracellular methionine, folate, and homocysteine, and its activity correlates with DNA methylation in many mammalian tissues. Our previous genomewide association study identified that 1 SNP located in the gene was associated with several wool production and quality traits in Chinese Merino. To confirm the potential involvement of the gene in sheep wool production and quality traits, we performed sheep tissue expression profiling, SNP detection, and association analysis with sheep wool production and quality traits. The semiquantitative reverse transcription PCR analysis showed that the gene was differentially expressed in skin from Merino and Kazak sheep. The sequencing analysis identified a total of 13 SNP in the gene from Chinese Merino sheep. Comparison of the allele frequencies revealed that these 13 identified SNP were significantly different among the 6 tested Chinese Merino strains ( < 0.001). Linkage disequilibrium analysis showed that SNP 3 to 11 were strongly linked in a single haplotype block in the tested population. Association analysis showed that SNP 2 to 11 were significantly associated with the average wool fiber diameter and the fineness SD and that SNP 4 to 11 were significantly associated with the CV of fiber diameter trait ( < 0.05). Single nucleotide polymorphism 2 and SNP 5 to 12 were weakly associated with wool crimp. Similarly, the haplotypes derived from these 13 identified SNP were also significantly associated with the average wool fiber diameter, fineness SD, and the CV of fiber diameter ( < 0.05). Our results suggest that is a candidate gene for sheep wool production and quality traits, and the identified SNP might be used in sheep breeding.

  15. Fibrinogen and associated risk factors in a high-risk population: urban Indigenous Australians, the DRUID Study.

    PubMed

    Maple-Brown, Louise J; Cunningham, Joan; Nandi, Nirjhar; Hodge, Allison; O'Dea, Kerin

    2010-10-29

    Epidemiological evidence suggests that fibrinogen and CRP are associated with coronary heart disease risk. High CRP in Indigenous Australians has been reported in previous studies including our 'Diabetes and Related diseases in Urban Indigenous population in Darwin region' (DRUID) Study. We studied levels of fibrinogen and its cross-sectional relationship with traditional and non-traditional cardiovascular risk factors in an urban Indigenous Australian cohort. Fibrinogen data were available from 287 males and 628 females (aged ≥ 15 years) from the DRUID study. Analysis was performed for associations with the following risk factors: diabetes, HbA1c, age, BMI, waist circumference, waist-hip ratio, total cholesterol, triglyceride, HDL cholesterol, C-reactive protein, homocysteine, blood pressure, heart rate, urine ACR, smoking status, alcohol abstinence. Fibrinogen generally increased with age in both genders; levels by age group were higher than those previously reported in other populations, including Native Americans. Fibrinogen was higher in those with than without diabetes (4.24 vs 3.56 g/L, p < 0.001). After adjusting for age and sex, the following were significantly associated with fibrinogen: BMI, waist, waist-hip ratio, systolic blood pressure, heart rate, fasting triglycerides, HDL cholesterol, HbA1c, CRP, ACR and alcohol abstinence. On multivariate regression (age and sex-adjusted) CRP and HbA1c were significant independent predictors of fibrinogen, explaining 27% of its variance; CRP alone explained 25% of fibrinogen variance. On factor analysis, both CRP and fibrinogen clustered with obesity in women (this factor explained 20% of variance); but in men, CRP clustered with obesity (factor explained 18% of variance) whilst fibrinogen clustered with HbA1c and urine ACR (factor explained 13% of variance). Fibrinogen is associated with traditional and non-traditional cardiovascular risk factors in this urban Indigenous cohort and may be a useful biomarker of

  16. Ancestry of the Timorese: age-related macular degeneration associated genotype and allele sharing among human populations from throughout the world

    PubMed Central

    Morrison, Margaux A.; Magalhaes, Tiago R.; Ramke, Jacqueline; Smith, Silvia E.; Ennis, Sean; Simpson, Claire L.; Portas, Laura; Murgia, Federico; Ahn, Jeeyun; Dardenne, Caitlin; Mayne, Katie; Robinson, Rosann; Morgan, Denise J.; Brian, Garry; Lee, Lucy; Woo, Se J.; Zacharaki, Fani; Tsironi, Evangelia E.; Miller, Joan W.; Kim, Ivana K.; Park, Kyu H.; Bailey-Wilson, Joan E.; Farrer, Lindsay A.; Stambolian, Dwight; DeAngelis, Margaret M.

    2015-01-01

    We observed that the third leading cause of blindness in the world, age-related macular degeneration (AMD), occurs at a very low documented frequency in a population-based cohort from Timor-Leste. Thus, we determined a complete catalog of the ancestry of the Timorese by analysis of whole exome chip data and haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in the Timorese to examine their allele frequencies compared to and between previously documented AMD cohorts of varying ethnicities. For those without AMD (average age > 55 years), genotype and allele frequencies were similar for most SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was at a significantly higher frequency in the Timorese, as well as 3 of the 5 protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally, the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen at a much lower frequency in the Korean and Timorese populations than in the assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in allele frequencies between the Timorese population and the other genotyped populations, along with the haplogroup analysis, also highlight the genetic diversity of the Timorese. Specifically, the most common ancestry groupings were Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The low prevalence of AMD in the Timorese population (2 of 535 randomly selected participants) may be due to the enrichment of protective alleles in this population at the 1q32 locus. PMID:26217379

  17. Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations.

    PubMed

    Gombos, Z; Hermann, R; Kiviniemi, M; Nejentsev, S; Reimand, K; Fadeyev, V; Peterson, P; Uibo, R; Ilonen, J

    2007-12-01

    Addison's disease is an organ-specific autoimmune disorder with a polygenic background. The aim of the study was to identify non-class II human leukocyte antigen (HLA) susceptibility genes for Addison's disease. Addison's disease patients from three European populations were analysed for selected HLA-DR-DQ alleles and for 11 microsatellite markers covering approximately 4 Mb over the HLA region. Subjects were 69 patients with Addison's disease from Estonia (24), Finland (14) and Russia (31). Consecutively recruited healthy newborns from the same geographical regions were used as controls (269 Estonian, 1000 Finnish and 413 Russian). Association measures for HLA-DRB1, DQB1, DQA1 and 11 microsatellites between D6S273 and D6S2223 were taken. A low-resolution full-house typing was used for HLA class II genes, while microsatellite markers were studied using fluorescence-based DNA fragment sizing technology. We confirmed that the HLA-DR3-DQ2 and the DQB1*0302-DRB1*0404 haplotypes confer disease susceptibility. In Russian patients, we also found an increase of DRB1*0403 allele, combined with DQB1*0305 allele in three out of six cases (P<0.0001). Analysis of 11 microsatellite markers including STR MICA confirmed the strong linkage in DR3-DQ2 haplotypes but DRB1*0404-DQB1*0302 haplotypes were diverse. MICA5.1 allele was found in 22 out of 24 Estonian patients, but results from Finnish and Russian patients did not support its independent role in disease susceptibility. HLA-DRB1*0403 was identified as a novel susceptibility allele for Addison's disease. Additionally, we found no evidence of a non-class II HLA disease susceptibility locus; however, the HLA-DR3-DQ2 haplotype appeared more conserved in patient groups with high DR-DQ2 frequencies.

  18. Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.

    PubMed

    Zhu, Hong; Xia, Wei; Mo, Xing-Bo; Lin, Xiang; Qiu, Ying-Hua; Yi, Neng-Jun; Zhang, Yong-Hong; Deng, Fei-Yan; Lei, Shu-Feng

    2016-01-01

    Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected 'highly verified' genes were measured by ELISA among our in-house RA cases and controls. A total of 221 RA-associated genes were newly identified by gene-based association study, including 71'overlapped', 76 'European-specific' and 74 'Asian-specific' genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 'overlapped' (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 'European-specific' (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 'Asian-specific' (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The

  19. Prevalence of atherogenic dyslipidemia: association with risk factors and cardiovascular risk in Spanish working population. "ICARIA" study.

    PubMed

    Cabrera, M; Sánchez-Chaparro, M A; Valdivielso, P; Quevedo-Aguado, L; Catalina-Romero, C; Fernández-Labandera, C; Ruiz-Moraga, M; González-Santos, P; Calvo-Bonacho, E

    2014-08-01

    The aim of this study was to assess the prevalence of atherogenic dyslipidemia (AD) and the lipid triad (LT) in the working population in Spain, their associated variables and how far they are linked to cardiovascular risk (CVR). Observational cross-sectional study of 70,609 workers (71.5% male (M), 28.5% female (F), mean age 39.2 ± 10), who attended medical checkups and agreed to participate. Plasma samples were analysed in a central laboratory. AD definition used was: triglycerides ≥150 mg/dl and HDL cholesterol <40 mg/dl (M)/<50 mg/dl (F) and LT when LDL cholesterol > 160 mg/dl is further added. Univariate comparisons in the absence and presence of AD and LT and the probability of AD according to different parameters and their possible association with CVR were assessed. CVR was stratified following the European SCORE model for low risk-population. 5.7% (95% CI 4.7-6.9) of the working population have AD and 1.1% (95% CI 1.0-1.2) LT. In univariate analysis, workers with AD and LT had a higher prevalence of obesity, hypertension, smoking and diabetes than those who had not (p < 0.001). In multivariate analysis, BMI, sex, age 40-49, diabetes, tobacco, uric acid, LDL or blood pressure significantly influenced the risk of AD. AD was significantly associated with CVR after adjusting for alcohol and obesity. However, most of the AD subjects (91.8%) were classified as low risk. About 6% of the working population in Spain meets AD criteria. Assuming that these subjects have increased CVR, AD allows to identify additional 5% of subjects with increased CVR to that one the SCORE model detects, helping to improve cardiovascular risk stratification. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Association between prostate cancer and urinary calculi: a population-based study.

    PubMed

    Chung, Shiu-Dong; Liu, Shih-Ping; Lin, Herng-Ching

    2013-01-01

    Understanding the reasons underlying the emerging trend and the changing demographics of Asian prostate cancer (PC) has become an important field of study. This study set out to explore the possibility that urinary calculi (UC) and PC may share an association by conducting a case-control study on a population-based database in Taiwan. The cases of this study included 2,900 subjects ≥ 40 years-old who had received their first-time diagnosis of PC and 14,500 randomly selected controls without PC. Conditional logistic regressions were employed to explore the association between PC and having been previously diagnosed with UC. We found that prior UC was found among 608 (21.0%) cases and 2,037 (14.1%) controls (p<0.001). Conditional logistic regression analysis revealed that compared to controls, the odds ratio (OR) of prior UC for cases was 1.63 (95% CI = 1.47-1.80). Furthermore, we found that cases were more likely to have been previously diagnosed with kidney calculus (OR = 1.71; 95% CI = 1.42-2.05), bladder calculus (OR = 2.06; 95% CI = 1.32-3.23), unspecified calculus (OR = 1.66; 95% CI = 1.37-2.00), and ≥2 locations of UC (OR = 1.73; 1.47-2.02) than controls. However, there was no significant relationship between PC and prior ureter calculus. We also found that of the patients with UC, there was no significant difference between PC and treatment method. This investigation detected an association between PC and prior UC. These results highlight a potential target population for PC screening.

  1. Prevalence of vitamin D deficiency and its associated factors among the urban elderly population in Hyderabad metropolitan city, South India.

    PubMed

    Suryanarayana, Palla; Arlappa, Nimmathota; Sai Santhosh, Vadakattu; Balakrishna, Nagalla; Lakshmi Rajkumar, Pondey; Prasad, Undrajavarapu; Raju, Banavath Bhoja; Shivakeseva, Kommula; Divya Shoshanni, Kondru; Seshacharyulu, Madabushi; Geddam, Jagjeevan Babu; Prasanthi, Prabhakaran Sobhana; Ananthan, Rajendran

    2018-03-01

    Deficiency of vitamin D has been associated with various health conditions. However, vitamin D deficiency (VDD) and factors associated with VDD are not well studied, especially among the urban elderly population of India. To assess the prevalence of VDD and its associated factors among the urban free-living elderly population in Hyderabad. A community-based cross-sectional study was conducted among 298 urban elderly (≥60 years) by adapting a random sampling procedure. Demographic particulars were collected. Blood pressure and anthropometric measurements were recorded using standard equipment. Fasting glucose, lipid profile and 25-hydroxy vitamin D [25(OH) D] were estimated in plasma samples. The mean ± SE plasma vitamin D and the prevalence of VDD among the urban elderly population were 19.3 ± 0.54 (ng/ml) and 56.3%, respectively. The prevalence of VDD was significantly associated with education, high body mass index (BMI), hypertension (HT) and metabolic syndrome (MS). Multiple logistic regression analysis revealed HT as a significant predictor of vitamin D deficiency and the risk of VDD was double among the elderly with hypertension. The prevalence of VDD was high among the urban elderly population in the south Indian city of Hyderabad. High BMI, MS, HT and education are significant associated factors of VDD.

  2. Genetic association of COL1A1 polymorphisms with high myopia in Asian population: a Meta-analysis

    PubMed Central

    Gong, Bo; Qu, Chao; Huang, Xiao-Fang; Ye, Zi-Meng; Zhang, Ding-Ding; Shi, Yi; Chen, Rong; Liu, Yu-Ping; Shuai, Ping

    2016-01-01

    AIM To comprehensively evaluate the potential association of COL1A1 polymorphisms with high myopia by a systematic review and Meta-analysis. METHODS All association studies on COL1A1 and high myopia reported up to June 10, 2014 in PubMed, Embase, Web of Science, and the Chinese Biomedical Database were retrieved. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were analyzed for single-nucleotide polymorphisms (SNPs) using fixed- and random- effects models according to between-study heterogeneity. Publication bias analyses were conducted by Egger's test. RESULTS A total of four studies from reported papers were included in this analysis. The Meta-analyses for COL1A1 rs2075555, composed of 2304 high myopia patients and 2272 controls, failed to detect any significant association with high myopia. A total of 971 cases and 649 controls were tested for COL1A1 rs2269336. The association of COL1A1 rs2269336 with high myopia was observed in recessive model (CC vs CG+GG, P=0.03) and in heterozygous model (CG vs GG, P=0.04), but not in other models. CONCLUSION This Meta-analysis shows that COL1A1 rs2269336 (CC vs CG+GG) affects individual susceptibility to high myopia, whereas there is no association detected between SNPs rs2075555 and high myopia. Given the limited sample size, further investigations including more ethnic groups are required to validate the association. PMID:27588274

  3. 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.

  4. Impacts of climate change on the population health associated with pluvial disaster

    NASA Astrophysics Data System (ADS)

    Pan, Tsung-Yi; Chang, Tsang-Jung; Cheng, Ke-Sheng; Lai, Jihn-Sung; Chang, Hsiang-Kuan; Wu, Yii-Chen; Ho, Hao-Wei

    2013-04-01

    Many metropolises located in lowlands suffer pluvial inundation disaster more than pluvial flood disaster. During the post-inundation period, some water-borne illnesses would be induced from the polluted area. For improving mitigation strategies, population health risk assessment is an important tool of post-inundation disaster management, especially in the countries suffering tropical cyclones and monsoon with high frequency. Locating in the hot zone of typhoon tracks in the Western Pacific, Taiwan suffers three to five typhoons annually. Furthermore, the trend of 24 global circulation models (GCMs) shows that climate change would enhance rainfall in Taiwan. The purpose of this study is to evaluate the impacts of climate change on the population health associated with pluvial disaster. This study applies the concept that risk is composed by hazard and vulnerability to assess the risk of the population health associated with pluvial disaster. Stochastic simulation of bi-variate Gamma distribution is developed to downscale the GCMs' monthly data to extreme rainfall event scale in time domain. According to A1B scenario in short-term period of climate change, two-dimensional overland-flow coupled with drainage systems simulation is performed based on a design extreme rainfall event to calculate the impacts of climate change on pluvial hazard to population health, including flood depth, velocity and the duration of flood recession. The environmental vulnerability for population health is carried out according to the factors of resident and environment. The risk matrix is applied to show the risk by composing the inundation hazards and vulnerabilities associated with population health. The Taipei City, the Capital of Taiwan, is selected as the case study because the highest density of population in Taiwan causes high exposure to the risk of water-borne illnesses. Through assessing the impacts of climate change on the population health associated with pluvial disaster of

  5. Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

    PubMed Central

    2011-01-01

    Background Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism. PMID:21569632

  6. [Variables associated with the use of dental services among preschool population in Spain: a national health survey analysis].

    PubMed

    Barriuso Lapresa, Laura; Sanz-Barbero, Belén

    2012-01-01

    oral health is integral to health from the eruption of the first tooth. To achieving, it is necessary an early establishment of healthy oral habits as regular dental checkups. In developed countries, caries is the most prevalent chronic pediatric disease and it may be increasing in preschool age. a) assessing prevalence of oral health services use among Spanish preschool population, b) quantifying and analyzing the existence of variability among autonomous community and c) identifying variables associated with such use. cross-sectional study about Spanish National health Survey (2006). 2,172 children aged between 2 and 5 years (both inclusive). have gone to dental services at least once during life. sociodemographic, self-referred dental health, habits and family socioeconomic status variables. Multivariate logistic regression analysis. 20.8% of Spanish preschoolers reported had attended dental services. Probability of use increased with age (OR: 1,88; IC:1,53-2,31), frequency of daily tooth brushing (three or more times per day vrs less than once: OR: 2,94; IC: 1,47-5,87) and presence of caries (OR: 2,60; IC: 1,22-5,51). There is a socioeconomic gradient about probability of use: it increased with family socioeconomic status measured by social class (low vrs high: OR: 0,41; IC: 0,19-0,86) and maternal educational level (OR: 1,62; IC: 1,13-2,32). There was not variability in the oral health services use attributable to the autonomous community. the use of dental health services among Spanish preschool population is lower than desirable. The promotion of its use should be intensified in children from disadvantaged families.

  7. Associations between suicidal behavior and childhood abuse and neglect: A meta-analysis.

    PubMed

    Liu, Jianbo; Fang, Yumin; Gong, Jingbo; Cui, Xilong; Meng, Tiantian; Xiao, Bo; He, Yuqiong; Shen, Yanmei; Luo, Xuerong

    2017-10-01

    Relationships of some types of childhood maltreatment and suicidal behavior remain controversial and inconclusive. Medline, Embase, PsycINFO and Cochrane library were searched for eligible studies, and the results were synthesized in meta-analyses. childhood maltreatment was associated positively with suicidal behavior in the total population and maltreatment subgroups. Emotional abuse had the strongest effect (OR =2.33, SMD =0.660, P<0.001). Subgroup analyses showed that the effects of childhood abuse (OR =1.55, SMD =0.523) and neglect (OR =1.25, SMD =0.31) were significant. According to the analysis of dichotomous outcomes, childhood maltreatment was associated positively with suicidal behavior in men and women (women: OR =4.84, P<0.001; men: OR =1.03, P<0.001). Among populations, childhood maltreatment had the strongest effect on suicidal behavior in the general population (OR =3.78, P<0.001). However, the analysis of continuous outcomes showed that the effect was strongest in patients with chronic schizophrenia (SMD =0.89, P<0.001). In addition, childhood maltreatment was associated positively with suicide attempt (OR =1.11, SMD =0.48, P<0.001), but not with suicidal ideation. Some subgroup samples were not sufficiently large. Childhood maltreatment increases the risk of suicidal behavior. Emotional abuse had the strongest effect among the five types of maltreatment. The risk of suicidal behavior is higher in the general population, women, and individuals with chronic schizophrenia who have histories of childhood maltreatment. Copyright © 2017. Published by Elsevier B.V.

  8. Determining Phenological Patterns Associated with the Onset of Senescence in a Wheat MAGIC Mapping Population.

    PubMed

    Camargo, Anyela V; Mott, Richard; Gardner, Keith A; Mackay, Ian J; Corke, Fiona; Doonan, John H; Kim, Jan T; Bentley, Alison R

    2016-01-01

    The appropriate timing of developmental transitions is critical for adapting many crops to their local climatic conditions. Therefore, understanding the genetic basis of different aspects of phenology could be useful in highlighting mechanisms underpinning adaptation, with implications in breeding for climate change. For bread wheat ( Triticum aestivum ), the transition from vegetative to reproductive growth, the start and rate of leaf senescence and the relative timing of different stages of flowering and grain filling all contribute to plant performance. In this study we screened under Smart house conditions a large, multi-founder "NIAB elite MAGIC" wheat population, to evaluate the genetic elements that influence the timing of developmental stages in European elite varieties. This panel of recombinant inbred lines was derived from eight parents that are or recently have been grown commercially in the UK and Northern Europe. We undertook a detailed temporal phenotypic analysis under Smart house conditions of the population and its parents, to try to identify known or novel Quantitative Trait Loci associated with variation in the timing of key phenological stages in senescence. This analysis resulted in the detection of QTL interactions with novel traits such the time between "half of ear emergence above flag leaf ligule" and the onset of senescence at the flag leaf as well as traits associated with plant morphology such as stem height. In addition, strong correlations between several traits and the onset of senescence of the flag leaf were identified. This work establishes the value of systematically phenotyping genetically unstructured populations to reveal the genetic architecture underlying morphological variation in commercial wheat.

  9. Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China.

    PubMed

    Ye, Jun-jie; Ma, Li; Yang, Li-juan; Wang, Jin-huan; Wang, Yue-li; Guo, Hai; Gong, Ning; Nie, Wen-hui; Zhao, Shu-hua

    2013-09-01

    There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

  10. 'Candidatus Phytoplasma phoenicium' associated with almond witches'-broom disease: from draft genome to genetic diversity among strain populations.

    PubMed

    Quaglino, Fabio; Kube, Michael; Jawhari, Maan; Abou-Jawdah, Yusuf; Siewert, Christin; Choueiri, Elia; Sobh, Hana; Casati, Paola; Tedeschi, Rosemarie; Lova, Marina Molino; Alma, Alberto; Bianco, Piero Attilio

    2015-07-30

    Almond witches'-broom (AlmWB), a devastating disease of almond, peach and nectarine in Lebanon, is associated with 'Candidatus Phytoplasma phoenicium'. In the present study, we generated a draft genome sequence of 'Ca. P. phoenicium' strain SA213, representative of phytoplasma strain populations from different host plants, and determined the genetic diversity among phytoplasma strain populations by phylogenetic analyses of 16S rRNA, groEL, tufB and inmp gene sequences. Sequence-based typing and phylogenetic analysis of the gene inmp, coding an integral membrane protein, distinguished AlmWB-associated phytoplasma strains originating from diverse host plants, whereas their 16S rRNA, tufB and groEL genes shared 100 % sequence identity. Moreover, dN/dS analysis indicated positive selection acting on inmp gene. Additionally, the analysis of 'Ca. P. phoenicium' draft genome revealed the presence of integral membrane proteins and effector-like proteins and potential candidates for interaction with hosts. One of the integral membrane proteins was predicted as BI-1, an inhibitor of apoptosis-promoting Bax factor. Bioinformatics analyses revealed the presence of putative BI-1 in draft and complete genomes of other 'Ca. Phytoplasma' species. The genetic diversity within 'Ca. P. phoenicium' strain populations in Lebanon suggested that AlmWB disease could be associated with phytoplasma strains derived from the adaptation of an original strain to diverse hosts. Moreover, the identification of a putative inhibitor of apoptosis-promoting Bax factor (BI-1) in 'Ca. P. phoenicium' draft genome and within genomes of other 'Ca. Phytoplasma' species suggested its potential role as a phytoplasma fitness-increasing factor by modification of the host-defense response.

  11. Factors associated with lower gait speed among the elderly living in a developing country: a cross-sectional population-based study.

    PubMed

    Busch, Telma de Almeida; Duarte, Yeda Aparecida; Pires Nunes, Daniella; Lebrão, Maria Lucia; Satya Naslavsky, Michel; dos Santos Rodrigues, Anelise; Amaro, Edson

    2015-04-01

    Among community-dwelling older adults, mean values for gait speed vary substantially depending not only on the population studied, but also on the methodology used. Despite the large number of studies published in developed countries, there are few population-based studies in developing countries with socioeconomic inequality and different health conditions, and this is the first study with a representative sample of population. To explore this, the association of lower gait speed with sociodemographic, anthropometric factors, mental status and physical health was incorporated participants' weight (main weight) in the analysis of population of community-dwelling older adults living in a developing country. This was a cross-sectional population based on a sample of 1112 older adults aged 60 years and over from Health, Wellbeing and Aging Study cohort 2010. Usual gait speed (s) to walk 3 meters was stratified by sex and height into quartiles. Multiple regression analysis was performed to investigate the independent effect of each factor associated with a slower usual gait speed. The average walking speed of the elderly was 0.81 m/s-0.78 m/s among women and 0.86 m/s among men. In the final model, the factors associated with lower gait speed were age (OR = 3.56), literacy (OR = 3.20), difficulty in one or more IADL (OR = 2.74), presence of cardiovascular disease (OR = 2.15) and sedentarism. When we consider the 50% slower, we can add the variables handgrip strength, and the presence of COPD. Gait speed is a clinical marker and an important measure of functional capacity among the elderly. Our findings suggest that lower walking speed is associated with age, education, but especially with modifiable factors such as impairment of IADL, physical inactivity and cardiovascular disease. These results reinforce how important it is for the elderly to remain active and healthy.

  12. Variants on 8q24 and prostate cancer risk in Chinese population: a meta-analysis.

    PubMed

    Ren, Xiao-Qiang; Zhang, Jian-Guo; Xin, Shi-Yong; Cheng, Tao; Li, Liang; Ren, Wei-Hua

    2015-01-01

    Previous studies have identified 8q24 as an important region to prostate cancer (PCa) susceptibility. The aim of this study was to investigate the role of six genetic variants on 8q24 (rs1447295, A; rs6983267, G; rs6983561, C; rs7837688, T; rs10090154, T and rs16901979, A) on PCa risk in Chinese population. Online electronic databases were searched to retrieve related articles concerning the association between 8q24 variants and PCa risk in men of Chinese population published between 2000 and 2014. Odds ratio (ORs) with its 95% correspondence interval (CI) were employed to assess the strength of association. Total eleven case-control studies were screened out, including 2624 PCa patients and 2438 healthy controls. Our results showed that three risk alleles of rs1447295 A (OR=1.35, 95% CI=1.19-1.53, P<0.00001), rs6983561 C (C vs. A: OR=1.41, 95% CI=1.21-1.63, P<0.00001) and rs10090154 T (T vs. C: OR=1.48, 95% CI=1.22-1.80, P<0.00001) on8q24 were significantly associated with PCa risk in Chinese population. Furthermore, genotypes of rs1447295, AA+AC; rs6983561, CC+AC and CC; rs10090154, TT+TC; and rs16901979, AA were associated with PCa as well (P<0.01). No association was found between rs6983267, rs7837688 and PCa risk. In conclusions, variants including rs1447295, rs6983561, rs10090154 and rs16901979 on 8q24 might be associated with PCa risk in Chinese population, indicating these four variations may contribute risk to this disease. This meta-analysis was the first study to assess the role of 8q24 variants on PCa risk in Chinese population.

  13. Paranoid Ideation and Violence: Meta-analysis of Individual Subject Data of 7 Population Surveys.

    PubMed

    Coid, Jeremy W; Ullrich, Simone; Bebbington, Paul; Fazel, Seena; Keers, Robert

    2016-07-01

    There is controversy whether associations between psychosis and violence are due to coexisting substance misuse and factors increasing risk in nonpsychotic persons. Recent studies in clinical samples have implicated independent effects of paranoid delusions. Research findings suggest that individual psychotic-like-experiences on the psychosis continuum in the general population are associated with violence; it remains unclear whether this association is due to psychiatric comorbidity. We pooled data from 7 UK general population surveys (n = 23 444) and conducted a meta-analysis of individual subject data. Further meta-analyses were performed to identify heterogeneity. Main exposure variables: 5 psychotic-like-experiences and a categorical measure of psychosis. Comorbidity was established through standardized self-report instruments. Information was collected on violence, severity, victims. Paranoid ideation was associated with violence (AOR 2.26, 95% CI 1.75-2.91), severity and frequency, even when controlling for effects of other psychotic-like-experiences. Associations were not explained by comorbid conditions, including substance dependence. Psychotic disorder was associated with violence and injury to the perpetrator but associations were explained by paranoid ideation. Individual associations between hypomania, thought insertion, hallucinations, and violence were nonsignificant after adjustments, and significantly associated only when comorbid with antisocial personality disorder. Strange experiences were only associated with intimate partner violence. Paranoid ideation on a psychosis-continuum in the general population was associated with violence. All other associations were explained by comorbidity. Further investigation should determine whether paranoid ideation among persons in the community require preventive interventions, similar to those presenting to mental health services. Nevertheless, risks are considerably increased for psychotic

  14. Prevalence and associated factors with alcohol use disorders among adults: a population-based study in southern Brazil.

    PubMed

    Reisdorfer, Emilene; Büchele, Fátima; Pires, Rodrigo Otávio Moretti; Boing, Antonio Fernando

    2012-09-01

    The study aimed to describe the prevalence of alcohol use disorders in an adult population from Brazil and its association with demographic, socioeconomic, behavioral variables and health conditions. A population-based cross-sectional survey was conducted with adults (20 to 59 years) of a medium-sized city in Southern Brazil with a random sample of 1,720 individuals. Cluster sampling was done in two stages: census tract first and household second. Alcohol use disorders were measured using the Alcohol Use Disorders Identification Test (AUDIT) and associations were tested with selected variables by Poisson Regression. Results of multivariate analysis were expressed as prevalence ratios. The prevalence of alcohol use disorders in the population was 18.4% (95% CI: 16.6% - 20.3%), higher among men (29.9%) than in women (9.3%). The prevalence of abstinence was 30.6%; 6.8% of respondents had already caused problems to themselves or to others after drinking; and 10.3% reported that a relative, friend or doctor had already shown concern on their drinking. After multivariate analysis, an association with alcohol use disorders remained for: being male, age 20 to 29 years, being single, declaring to be light-skinned blacks and being an ex-smoker or current smoker. The prevalence of alcohol use disorders identified is high compared with other similar studies, with differences according to being male, age 20 to 29, skin color and tobacco use. These issues must be considered in formulating public health policies aimed at reducing problems related to alcohol use.

  15. Population Structure, Diversity and Trait Association Analysis in Rice (Oryza sativa L.) Germplasm for Early Seedling Vigor (ESV) Using Trait Linked SSR Markers

    PubMed Central

    Anandan, Annamalai; Anumalla, Mahender; Pradhan, Sharat Kumar; Ali, Jauhar

    2016-01-01

    Early seedling vigor (ESV) is the essential trait for direct seeded rice to dominate and smother the weed growth. In this regard, 629 rice genotypes were studied for their morphological and physiological responses in the field under direct seeded aerobic situation on 14th, 28th and 56th days after sowing (DAS). It was determined that the early observations taken on 14th and 28th DAS were reliable estimators to study ESV as compared to56th DAS. Further, 96 were selected from 629 genotypes by principal component (PCA) and discriminate function analyses. The selected genotypes were subjected to decipher the pattern of genetic diversity in terms of both phenotypic and genotypic by using ESV QTL linked simple sequence repeat (SSR) markers. To assess the genetic structure, model and distance based approaches were used. Genotyping of 96 rice lines using 39 polymorphic SSRs produced a total of 128 alleles with the phenotypic information content (PIC) value of 0.24. The model based population structure approach grouped the accession into two distinct populations, whereas unrooted tree grouped the genotypes into three clusters. Both model based and structure based approach had clearly distinguished the early vigor genotypes from non-early vigor genotypes. Association analysis revealed that 16 and 10 SSRs showed significant association with ESV traits by general linear model (GLM) and mixed linear model (MLM) approaches respectively. Marker alleles on chromosome 2 were associated with shoot dry weight on 28 DAS, vigor index on 14 and 28 DAS. Improvement in the rate of seedling growth will be useful for identifying rice genotypes acquiescent to direct seeded conditions through marker-assisted selection. PMID:27031620

  16. Using population mixtures to optimize the utility of genomic databases: linkage disequilibrium and association study design in India.

    PubMed

    Pemberton, T J; Jakobsson, M; Conrad, D F; Coop, G; Wall, J D; Pritchard, J K; Patel, P I; Rosenberg, N A

    2008-07-01

    When performing association studies in populations that have not been the focus of large-scale investigations of haplotype variation, it is often helpful to rely on genomic databases in other populations for study design and analysis - such as in the selection of tag SNPs and in the imputation of missing genotypes. One way of improving the use of these databases is to rely on a mixture of database samples that is similar to the population of interest, rather than using the single most similar database sample. We demonstrate the effectiveness of the mixture approach in the application of African, European, and East Asian HapMap samples for tag SNP selection in populations from India, a genetically intermediate region underrepresented in genomic studies of haplotype variation.

  17. A unified genetic association test robust to latent population structure for a count phenotype.

    PubMed

    Song, Minsun

    2018-06-04

    Confounding caused by latent population structure in genome-wide association studies has been a big concern despite the success of genome-wide association studies at identifying genetic variants associated with complex diseases. In particular, because of the growing interest in association mapping using count phenotype data, it would be interesting to develop a testing framework for genetic associations that is immune to population structure when phenotype data consist of count measurements. Here, I propose a solution for testing associations between single nucleotide polymorphisms and a count phenotype in the presence of an arbitrary population structure. I consider a classical range of models for count phenotype data. Under these models, a unified test for genetic associations that protects against confounding was derived. An algorithm was developed to efficiently estimate the parameters that are required to fit the proposed model. I illustrate the proposed approach using simulation studies and an empirical study. Both simulated and real-data examples suggest that the proposed method successfully corrects population structure. Copyright © 2018 John Wiley & Sons, Ltd.

  18. PCSK1 rs6232 is associated with childhood and adult class III obesity in the Mexican population.

    PubMed

    Villalobos-Comparán, Marisela; Villamil-Ramírez, Hugo; Villarreal-Molina, Teresa; Larrieta-Carrasco, Elena; León-Mimila, Paola; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Liceaga-Fuentes, Adriana E; Campos-Pérez, Francisco J; López-Contreras, Blanca E; Tusié-Luna, Teresa; Del Río-Navarro, Blanca E; Aguilar-Salinas, Carlos A; Canizales-Quinteros, Samuel

    2012-01-01

    Common variants rs6232 and rs6235 in the PCSK1 gene have been associated with obesity in European populations. We aimed to evaluate the contribution of these variants to obesity and related traits in Mexican children and adults. Rs6232 and rs6235 were genotyped in 2382 individuals, 1206 children and 1176 adults. Minor allele frequencies were 0.78% for rs6232 and 19.99% for rs6235. Rs6232 was significantly associated with childhood obesity and adult class III obesity (OR = 3.01 95%CI 1.64-5.53; P = 4 × 10⁻⁴ in the combined analysis). In addition, this SNP was significantly associated with lower fasting glucose levels (P = 0.01) and with increased insulin levels and HOMA-B (P = 0.05 and 0.01, respectively) only in non-obese children. In contrast, rs6235 showed no significant association with obesity or with glucose homeostasis parameters in any group. Although rs6232 is rare in the Mexican population, it should be considered as an important risk factor for extreme forms of obesity.

  19. Association between obesity and depressive symptoms in Mexican population.

    PubMed

    Zavala, Gerardo A; Kolovos, Spyros; Chiarotto, Alessandro; Bosmans, Judith E; Campos-Ponce, Maiza; Rosado, Jorge L; Garcia, Olga P

    2018-06-01

    Obesity and depression are among the leading causes of disability in Mexico, but their association has not been explored yet. The aim of the current study was to investigate the association between obesity and depression in Mexican population. We used data from the health and nutrition survey (ENSANUT 2012), which is representative of the Mexican population. Obesity was determined using the body mass index (BMI) and abdominal obesity by measuring waist circumference. Depressive symptoms were reported using the Center for Epidemiological Studies Depression Scale Short-Form (CES-D-SF, scale 0-21). Regression analyses were performed between obesity and depression, adjusting for gender, age, living with a partner, education, and diabetes history. Obese women had 1.28 (95% CI 1.07-1.53) times the odds of having depression in comparison with normal-weight women, whereas no association was found for men (OR 0.94; 95% CI 0.74-1.19). A significant association between BMI and depressive symptoms score (β = 0.05, 95% CI 0.02-0.07) was present in women, but no association was found for men (β = - 0.02, 95% CI - 0.05 to 0.00). There was a statistically significant association between waist circumference and depression scores again for women (β = 0.03, 95% CI 0.01-0.04) but not for men (β = 0.00, 95% CI - 0.01 to 0.01). No associations were found between abdominal obesity and depression for both genders. No association was found between different obesity severity levels and depression for both genders. Obesity was associated with depression in Mexican women, whereas no association was found between obesity and depression in men.

  20. Associations between behavioural risk factors and overweight and obesity among adults in population-based samples from 31 countries.

    PubMed

    Pengpid, Supa; Peltzer, Karl

    Concern about overweight and obesity is growing worldwide, and more research to examine behaviours associated with the risk for increased weight in adult populations is needed. The aim of this study was to estimate associations between behavioural risk factors and overweight and obesity among adults in nationally representative population samples from 20 countries in Europe, 8 countries in Asia, Australia, Chile and USA. This secondary analysis is based on the International Social Survey Program (ISSP), 2011-2013, Health and Health Care Module. In a cross-sectional population-based survey (N=48,741) (mean age 46.6 years, SD=17.4, age range 15-102 years) simple or multi-stage stratified random sampling was used, yielding representative samples of the adult population of respective countries. Body Mass Index was assessed by self-reported height and weight. Correlates were risk behaviours for chronic disease (smoking status, alcohol intake, consumption of fruits and vegetable (=FV), and physical activity). Overall, for all 31 countries the prevalence of overweight or obesity was 44.1%, 31.7% overweight and 12.4% obese. In adjusted logistic regression models, among men and among women ex-smoking was positively associated with both overweight and obesity, while light or moderate smoking overall and among men were inversely related with obesity. Moderate alcohol use was positively associated with both overweight and obesity, while heavy alcohol use was negatively associated with overweight. The daily consumption of FV was found to be protective from both overweight and obesity, overall and for men but not for women. Physical activity was positively associated with overweight but not obesity. Some risk behaviours for chronic disease appear to be associated with overweight and obesity among adults. Interventions targeting these risk behaviours may have the potential to reduce weight. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier

  1. A Method for Inferring an Individual’s Genetic Ancestry and Degree of Admixture Associated with Six Major Continental Populations

    PubMed Central

    Libiger, Ondrej; Schork, Nicholas J.

    2013-01-01

    The determination of the ancestry and genetic backgrounds of the subjects in genetic and general epidemiology studies is a crucial component in the analysis of relevant outcomes or associations. Although there are many methods for differentiating ancestral subgroups among individuals based on genetic markers only a few of these methods provide actual estimates of the fraction of an individual’s genome that is likely to be associated with different ancestral populations. We propose a method for assigning ancestry that works in stages to refine estimates of ancestral population contributions to individual genomes. The method leverages genotype data in the public domain obtained from individuals with known ancestries. Although we showcase the method in the assessment of ancestral genome proportions leveraging largely continental populations, the strategy can be used for assessing within-continent or more subtle ancestral origins with the appropriate data. PMID:23335941

  2. Socioeconomic factors associated with drug consumption in prison population in Mexico.

    PubMed

    Nevárez-Sida, Armando; Constantino-Casas, Patricia; Castro-Ríos, Angélica

    2012-01-13

    Consumption of illegal drugs is a public health problem in Mexico, and the prison population is a vulnerable group with higher rates of prevalence than in the general population. The objective of this study was to determine the main socioeconomic variables associated with drug consumption in the prison population. Utilizing data from the Second Incarcerated Population Survey carried out by the Centre of Research and Teaching of Economics (CIDE) in Mexico, a logistic model in two stages was developed. The first stage analyzed the determinants of habitual drug consumption by prisoners (prior to admittance into prisons), while the second stage of the model addressed drug consumption within prisons. Prevalence of drug consumption previous to incarceration was 28.5%, although once people were imprisoned this figure dropped to 7.4%. The characteristics that most heavily influenced against the possibility of habitual drug consumption prior to admittance to prison were: preparatory school or higher, being employed and having children; while the variables associated negatively were: male gender, childhood home shared with adults who consumed illegal drugs; abandoning childhood home; and having previous prison sentences. Once in prison, the negative conditions in there are associated with drug consumption. Work and study during incarceration, in addition to being instruments for rehabilitation, seem to exert an important positive association against drug consumption. However, this correlation seems to be minimized in the face of negative conditions of the penal institution; thus, public policies are necessary to improve the prisoner's environment.

  3. Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

    PubMed

    Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

    2013-04-01

    Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

  4. Association for population/family planning libraries and information centers-international (APLIC).

    PubMed

    Shipman, P E

    1983-04-01

    Population centers and their information units or libraries were established as early as the 1920s, but population evolved as a field of study in its own right mainly during the 1950s and 60s. This paper attempts not so much to describe all that has taken place in the population information field to date, as to describe the activities of the Association for Population/Family Planning Libraries and Information Centers-International (APLIC). It is 1 of 2 international associations of population/family planning information specialists; the other is POPIN, in whose establishment APLIC played a key role. Membership can be either individual or institutional. At present there are 129 members from all parts of the globe. APLIC's goal is to make population, demographic, and family planning information available in the most effective way to researchers, policy-makers, clinicians, administrators, and program practitioners throughout the world. Its efforts are focused on 5 major areas: 1) the development of effective documentation and information systems and services; 2) professional contact among population librarians, documentalists, and information and communication specialists; 3) the global exchange of population information through programs and activities; 4) a cooperative network of population documentation centers and libraries; 5) continuing education to encourage professional development. Every year since 1968, APLIC has held a conference at which a diverse number of international and national information topics have been dealt with, and at which there have been working committees and information panels. Other activities include the publication of a newsletter, inter-library loans, reference services, and other matters relating to respective parent organizations.

  5. Loci associated with skin pigmentation identified in African populations

    PubMed Central

    Crawford, Nicholas G.; Kelly, Derek E.; Hansen, Matthew E. B.; Beltrame, Marcia H.; Fan, Shaohua; Bowman, Shanna L.; Jewett, Ethan; Ranciaro, Alessia; Thompson, Simon; Lo, Yancy; Pfeifer, Susanne P.; Jensen, Jeffrey D.; Campbell, Michael C.; Beggs, William; Hormozdiari, Farhad; Mpoloka, Sununguko Wata; Mokone, Gaonyadiwe George; Nyambo, Thomas; Meskel, Dawit Wolde; Belay, Gurja; Haut, Jake; Rothschild, Harriet; Zon, Leonard; Zhou, Yi; Kovacs, Michael A.; Xu, Mai; Zhang, Tongwu; Bishop, Kevin; Sinclair, Jason; Rivas, Cecilia; Elliot, Eugene; Choi, Jiyeon; Li, Shengchao A.; Hicks, Belynda; Burgess, Shawn; Abnet, Christian; Watkins-Chow, Dawn E.; Oceana, Elena; Song, Yun S.; Eskin, Eleazar; Brown, Kevin M.; Marks, Michael S.; Loftus, Stacie K.; Pavan, William J.; Yeager, Meredith; Chanock, Stephen; Tishkoff, Sarah

    2017-01-01

    Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2 and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in southern Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of UV response genes under selection in Eurasians. PMID:29025994

  6. Place matters: A longitudinal analysis measuring the association between neighbourhood walkability and walking by age group and population center size in Canada

    PubMed Central

    Steinmetz-Wood, Madeleine; Kestens, Yan

    2017-01-01

    This study examined the influence of walkability on walking behaviour and assessed whether associations varied according to life-stage and population center (PC) size. Walkability scores were obtained for the six-digit postal codes of residential neighbourhoods of 11,200 Canadians, who participated in biennial assessments of the National Population Health Survey from 1994 to 2010. Participants were stratified by age-group. Mixed-effects logistic regression models were used to estimate the influence of cumulative exposure to neighborhood walkability on utilitarian and exercise walking by PC size and life-stage. Associations of neighbourhood walkability with utilitarian and exercise walking varied according to age-group and PC size. Exposure to high walkable neighborhoods was associated with utilitarian walking in younger and older adults in all PC sizes, except for older adults living in a medium PC. Living in a highly walkable neighborhood in a large PC was associated with walking for exercise in younger (OR: 1.42; 95%CI: 1.20–1.67) and older adults (OR: 2.09; 95%CI: 1.51–2.89). Living in highly walkable neighbourhood in a medium PC was associated with walking for exercise in older adults (OR: 1.62; 95%CI: 1.15–2.29). These results emphasize the need to consider the size and nature of every community, and the age-group of a population when implementing strategies to promote walking. PMID:29261706

  7. Modeling association among demographic parameters in analysis of open population capture-recapture data.

    PubMed

    Link, William A; Barker, Richard J

    2005-03-01

    We present a hierarchical extension of the Cormack-Jolly-Seber (CJS) model for open population capture-recapture data. In addition to recaptures of marked animals, we model first captures of animals and losses on capture. The parameter set includes capture probabilities, survival rates, and birth rates. The survival rates and birth rates are treated as a random sample from a bivariate distribution, thus the model explicitly incorporates correlation in these demographic rates. A key feature of the model is that the likelihood function, which includes a CJS model factor, is expressed entirely in terms of identifiable parameters; losses on capture can be factored out of the model. Since the computational complexity of classical likelihood methods is prohibitive, we use Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient candidate-generation scheme for Metropolis-Hastings sampling of CJS models and extensions. The procedure is illustrated using mark-recapture data for the moth Gonodontis bidentata.

  8. Modeling association among demographic parameters in analysis of open population capture-recapture data

    USGS Publications Warehouse

    Link, William A.; Barker, Richard J.

    2005-01-01

    We present a hierarchical extension of the Cormack–Jolly–Seber (CJS) model for open population capture–recapture data. In addition to recaptures of marked animals, we model first captures of animals and losses on capture. The parameter set includes capture probabilities, survival rates, and birth rates. The survival rates and birth rates are treated as a random sample from a bivariate distribution, thus the model explicitly incorporates correlation in these demographic rates. A key feature of the model is that the likelihood function, which includes a CJS model factor, is expressed entirely in terms of identifiable parameters; losses on capture can be factored out of the model. Since the computational complexity of classical likelihood methods is prohibitive, we use Markov chain Monte Carlo in a Bayesian analysis. We describe an efficient candidate-generation scheme for Metropolis–Hastings sampling of CJS models and extensions. The procedure is illustrated using mark-recapture data for the moth Gonodontis bidentata.

  9. Genetic analysis of Mexican Criollo cattle populations.

    PubMed

    Ulloa-Arvizu, R; Gayosso-Vázquez, A; Ramos-Kuri, M; Estrada, F J; Montaño, M; Alonso, R A

    2008-10-01

    The objective of this study was to evaluate the genetic structure of Mexican Criollo cattle populations using microsatellite genetic markers. DNA samples were collected from 168 animals from four Mexican Criollo cattle populations, geographically isolated in remote areas of Sierra Madre Occidental (West Highlands). Also were included samples from two breeds with Iberian origin: the fighting bull (n = 24) and the milking central American Criollo (n = 24) and one Asiatic breed: Guzerat (n = 32). Genetic analysis consisted of the estimation of the genetic diversity in each population by the allele number and the average expected heterozygosity found in nine microsatellite loci. Furthermore, genetic relationships among the populations were defined by their genetic distances. Our data shows that Mexican cattle populations have a relatively high level of genetic diversity based either on the mean number of alleles (10.2-13.6) and on the expected heterozygosity (0.71-0.85). The degree of observed homozygosity within the Criollo populations was remarkable and probably caused by inbreeding (reduced effective population size) possibly due to reproductive structure within populations. Our data shows that considerable genetic differentiation has been occurred among the Criollo cattle populations in different regions of Mexico.

  10. A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

    PubMed Central

    Zhang, Han; Wheeler, William; Hyland, Paula L.; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

    2016-01-01

    Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID:27362418

  11. A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.

    PubMed

    Zhang, Han; Wheeler, William; Hyland, Paula L; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

    2016-06-01

    Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs.

  12. Genetic polymorphisms in ALDH2 are associated with drug addiction in a Chinese Han population

    PubMed Central

    Zhang, Chan; Ding, Heng; Cheng, Yujing; Chen, Wanlu; Li, Qi; Li, Qing; Dai, Run; Luo, Manlin

    2017-01-01

    We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2, which has been associated with alcohol dependence and several types of diseases, and the risk of drug addiction in a Chinese Han population. In a case-control study that included 692 cases and 700 healthy controls, eight SNPs in ALDH2 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. We determined that rs671 is significantly associated with a 1.551-fold increased drug addiction risk (95% CI = 1.263-1.903; p < 0.001). In the genetic model analysis, we found that rs671 is associated with an increased risk of drug addiction under additive, dominant and recessive models (p < 0.001), while rs886205, rs441 and rs4646778 displayed a decreased drug addiction risk under additive and recessive model, respectively (p < 0.05). SNP rs671 remained significant after Bonferroni correction (p<0.00125). Additionally, we observed that haplotype “GTCAC” was associated with increased drug addiction risk (OR = 1.668; 95% CI, 1.328–2.094, p < 0.001); in contrast, “ATCGC” was a protective haplotype for drug addiction risk (OR = 0.444; 95% CI, 0.281–0.704, p < 0.001). Our findings showed that ALDH2 polymorphisms are significantly associated with the risk of drug addiction in the Chinese Han population. PMID:28052001

  13. Genetic polymorphisms in ALDH2 are associated with drug addiction in a Chinese Han population.

    PubMed

    Zhang, Chan; Ding, Heng; Cheng, Yujing; Chen, Wanlu; Li, Qi; Li, Qing; Dai, Run; Luo, Manlin

    2017-01-31

    We investigated the association between single nucleotide polymorphisms (SNPs) in ALDH2, which has been associated with alcohol dependence and several types of diseases, and the risk of drug addiction in a Chinese Han population. In a case-control study that included 692 cases and 700 healthy controls, eight SNPs in ALDH2 were selected and genotyped using the Sequenom MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression after adjusting for age and gender. We determined that rs671 is significantly associated with a 1.551-fold increased drug addiction risk (95% CI = 1.263-1.903; p < 0.001). In the genetic model analysis, we found that rs671 is associated with an increased risk of drug addiction under additive, dominant and recessive models (p < 0.001), while rs886205, rs441 and rs4646778 displayed a decreased drug addiction risk under additive and recessive model, respectively (p < 0.05). SNP rs671 remained significant after Bonferroni correction (p<0.00125). Additionally, we observed that haplotype "GTCAC" was associated with increased drug addiction risk (OR = 1.668; 95% CI, 1.328-2.094, p < 0.001); in contrast, "ATCGC" was a protective haplotype for drug addiction risk (OR = 0.444; 95% CI, 0.281-0.704, p < 0.001). Our findings showed that ALDH2 polymorphisms are significantly associated with the risk of drug addiction in the Chinese Han population.

  14. [Family-based association study of a variable number of tandem repeat polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population].

    PubMed

    Zheng, Lanlan; Han, Zhen-liang; Zhang, Xin-hua; Wang, Xue-qin; Jiang, Wei-hua; Yi, Ming-ji; Liu, Shi-guo

    2013-10-01

    To assess the association of a 40 bp variable number of tandem repeat (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene (DAT1) with Tourette syndrome (TS) in a Chinese Han population. A total of 160 TS patients and their parents were recruited. The VNTR polymorphism was detected with polymerase chain reaction-VNTR analysis, and its association with TS and its subtypes were assessed through a family-based association study comprising transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analysis. The repeat numbers at the DAT1 40 bp locus were 11, 10, 9, 7.5 and 7 among the patients and their parents, with the most common type being a 10-repeat allele. No significant association was detected between the polymorphism and TS (TDT: X ² = 0.472, df = 1, P = 0.583; HRR: X ² = 0.313, P = 0.576, OR = 0.855, 95%CI: 0.493-1.481). Our data suggested that the VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in Chinese Han population. However, our results are to be validated in larger sets of patients collected from other populations.

  15. Assessing population exposure for landslide risk analysis using dasymetric cartography

    NASA Astrophysics Data System (ADS)

    Garcia, Ricardo A. C.; Oliveira, Sérgio C.; Zêzere, José L.

    2016-12-01

    Assessing the number and locations of exposed people is a crucial step in landslide risk management and emergency planning. The available population statistical data frequently have insufficient detail for an accurate assessment of potentially exposed people to hazardous events, mainly when they occur at the local scale, such as with landslides. The present study aims to apply dasymetric cartography to improving population spatial resolution and to assess the potentially exposed population. An additional objective is to compare the results with those obtained with a more common approach that uses, as spatial units, basic census units, which are the best spatial data disaggregation and detailed information available for regional studies in Portugal. Considering the Portuguese census data and a layer of residential building footprint, which was used as ancillary information, the number of exposed inhabitants differs significantly according to the approach used. When the census unit approach is used, considering the three highest landslide susceptible classes, the number of exposed inhabitants is in general overestimated. Despite the associated uncertainties of a general cost-benefit analysis, the presented methodology seems to be a reliable approach for gaining a first approximation of a more detailed estimation of exposed people. The approach based on dasymetric cartography allows the spatial resolution of population over large areas to be increased and enables the use of detailed landslide susceptibility maps, which are valuable for improving the exposed population assessment.

  16. Common PCSK1 haplotypes are associated with obesity in the Chinese population.

    PubMed

    Chang, Yi-Cheng; Chiu, Yen-Feng; Shih, Kuang-Chung; Lin, Ming-Wei; Sheu, Wayne Huey-Herng; Donlon, Timothy; Curb, Jess David; Jou, Yuh-Shan; Chang, Tien-Jyun; Li, Hung-Yuan; Chuang, Lee-Ming

    2010-07-01

    Prohormone convertase subtilisin/kexin type 1 (PCSK1) genetic polymorphisms have recently been associated with obesity in European populations. This study aimed to examine whether common PCSK1 genetic variation is associated with obesity and related metabolic phenotypes in the Chinese population. We genotyped nine common tag single-nucleotide polymorphisms (tagSNP) of the PCSK1 gene in 1,094 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. One SNP in the PCSK1 gene (rs155971) were nominally associated with risk of obesity in the SAPPHIRe cohort (P = 0.01). A common protective haplotype was associated with reduced risk of obesity (23.79% vs. 32.89%, P = 0.01) and smaller waist circumference (81.71 +/- 10.22 vs. 84.75 +/- 10.48 cm, P = 0.02). Another common haplotype was significantly associated with increased risk of obesity (37.07% vs. 23.84%, P = 0.005). The global P value for haplotype association with obesity was 0.02. We also identified a suggestive association of another PCSK1 SNP (rs3811951) with fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), triglycerides, and high-density lipoprotein cholesterol (P = 0.05, 0.003, 0.001, 0.04, and 0.04, respectively). These data indicate common PCSK1 genetic variants are associated with obesity in the Chinese population.

  17. Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations.

    PubMed

    Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

    2014-10-01

    Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population.

  18. Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations

    PubMed Central

    Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

    2014-01-01

    Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case–control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11–0.15) and cancer cases (0.14, 95% CI=0.12–0.16) compared with controls (0.11, 95% CI=0.10–0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97–1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05–1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population. PMID:24518838

  19. PRKCZ methylation is associated with sunlight exposure in a North American but not a Mediterranean population

    PubMed Central

    Aslibekyan, Stella; Dashti, Hassan S.; Tanaka, Toshiko; Sha, Jin; Ferrucci, Luigi; Zhi, Degui; Bandinelli, Stefania; Borecki, Ingrid B.; Absher, Devin M.; Arnett, Donna K.; Ordovas, Jose M.

    2015-01-01

    Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight exposure warrant investigation. The purpose of this study was to assess the effects of sunlight exposure on CD4+ T-cell methylation patterns on an epigenome-wide scale in a North American population of European origin (n = 991). In addition, we investigated the genetic contribution to epigenetic variation (methylQTL). We used linear regression to test the associations between methylation scores at 461 281 cytosine-phosphate-guanine (CpG) sites and sunlight exposure, followed by a genome-wide association analysis (methylQTL) to test for associations between methylation at the top CpG locus and common genetic variants, assuming an additive genetic model. We observed an epigenome-wide significant association between sunlight exposure and methylation status at cg26930596 (p = 9.2 × 10−8), a CpG site located in protein kinase C zeta (PRKCZ), a gene previously shown to be entrained by light. MethylQTL analysis resulted in significant associations between cg26930596 and two intergenic single nucleotide polymorphisms on chromosome 3, rs4574216 (p = 1.5 × 10−10) and rs4405858 (p = 1.9 × 10−9). These common genetic variants reside downstream of WWTR1, a transcriptional co-activator of PRKCZ. Associations observed in the North American population, however, did not replicate in an independent Mediterranean cohort. Our preliminary results support the role of sunlight exposure in epigenetic processes, and lay the groundwork for future studies of the molecular link between sunlight and physiologic processes such as tumorigenesis and metabolism. PMID:25075435

  20. Association between Hypertension and Epistaxis: Systematic Review and Meta-analysis.

    PubMed

    Min, Hyun Jin; Kang, Hyun; Choi, Geun Joo; Kim, Kyung Soo

    2017-12-01

    Objective Whether there is an association or a cause-and-effect relationship between epistaxis and hypertension is a subject of longstanding controversy. The objective of this systematic review and meta-analysis was to determine the association between epistaxis and hypertension and to verify whether hypertension is an independent risk factor of epistaxis. Data Sources A comprehensive search was performed using the MEDLINE, EMBASE, and Cochrane Library databases. Review Methods The review was performed according to the Meta-analysis of Observational Studies in Epidemiology guidelines and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Results We screened 2768 unique studies and selected 10 for this meta-analysis. Overall, the risk of epistaxis was significantly increased for patients with hypertension (odds ratio, 1.532 [95% confidence interval (CI), 1.181-1.986]; number needed to treat, 14.9 [95% CI, 12.3-19.0]). Results of the Q test and I 2 statistics suggested considerable heterogeneity ([Formula: see text] = 0.038, I 2 = 49.3%). The sensitivity analysis was performed by excluding 1 study at a time, and it revealed no change in statistical significance. Conclusion Although this meta-analysis had some limitations, our study demonstrated that hypertension was significantly associated with the risk of epistaxis. However, since this association does not support a causal relationship between hypertension and epistaxis, further clinical trials with large patient populations will be required to determine the impact of hypertension on epistaxis.

  1. Mosquito populations dynamics associated with climate variations.

    PubMed

    Wilke, André Barretto Bruno; Medeiros-Sousa, Antônio Ralph; Ceretti-Junior, Walter; Marrelli, Mauro Toledo

    2017-02-01

    Mosquitoes are responsible for the transmission of numerous serious pathogens. Members of the Aedes and Culex genera, which include many important vectors of mosquito-borne diseases, are highly invasive and adapted to man-made environments. They are spread around the world involuntarily by humans and are highly adapted to urbanized environments, where they are exposed to climate-related abundance drivers. We investigated Culicidae fauna in two urban parks in the city of São Paulo to analyze the correlations between climatic variables and the population dynamics of mosquitoes in these urban areas. Mosquitoes were collected monthly over one year, and sampling sufficiency was evaluated after morphological identification of the specimens. The average monthly temperature and accumulated rainfall for the collection month and previous month were used to explain climate-related abundance drivers for the six most abundant species (Aedes aegypti, Aedes albopictus, Aedes fluviatilis, Aedes scapularis, Culex nigripalpus and Culex quinquefasciatus) and then analyzed using generalized linear statistical models and the Akaike Information Criteria corrected for small samples (AICc). The strength of evidence in favor of each model was evaluated using Akaike weights, and the explanatory model power was measured by McFadden's Pseudo-R 2 . Associations between climate and mosquito abundance were found in both parks, indicating that predictive models based on climate variables can provide important information on mosquito population dynamics. We also found that this association is species-dependent. Urbanization processes increase the abundance of a few mosquito species that are well adapted to man-made environments and some of which are important vectors of pathogens. Predictive models for abundance based on climate variables may help elucidate the population dynamics of urban mosquitoes and their impact on the risk of disease transmission, allowing better predictive scenarios to be

  2. Analysis of promoter polymorphism in monoamine oxidase A (MAOA) gene in completed suicide on Slovenian population.

    PubMed

    Uršič, Katarina; Zupanc, Tomaž; Paska, Alja Videtič

    2018-04-23

    Suicide is a well-defined public health problem and is a complex phenomenon influenced by a number of different risk factors, including genetic ones. Numerous studies have examined serotonin system genes. Monoamine oxidase A (MAO-A) is an outer mitochondrial membrane enzyme which is involved in the metabolic pathway of serotonin degradation. Upstream variable number of tandem repeats (uVNTR) in the promoter region of MAOA gene affects the activity of transcription. In the present study we genotyped MAOA-uVNTR polymorphism in 266 suicide victims and 191 control subjects of Slovenian population, which ranks among the European and world populations with the highest suicide rate. Genotyping was performed with polymerase chain reaction and agarose gel electrophoresis. Using a separate statistical analysis for female and male subjects we determined the differences in genotype distributions of MAOA-uVNTR polymorphism between the studied groups. Statistical analysis showed a trend towards 3R allele and suicide, and associated 3R allele with non-violent suicide method on stratified data (20 suicide victims). This is the first study associating highly suicidal Slovenian population with MAOA-uVNTR polymorphism. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population

    PubMed Central

    Sun, Congcong; Wei, Lei; Luo, Feifei; Li, Yi; Li, Jiaobiao; Zhu, Feiqi; Kang, Ping; Xu, Rensi; Xiao, LuLu; Liu, Zhuolin; Xu, Pingyi

    2012-01-01

    Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The χ2 test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate. PMID:23139797

  4. National socioeconomic indicators are associated with outcomes after aneurysmal subarachnoid hemorrhage: a hierarchical mixed-effects analysis.

    PubMed

    Guha, Daipayan; Ibrahim, George M; Kertzer, Joshua D; Macdonald, R Loch

    2014-11-01

    Although heterogeneity exists in patient outcomes following subarachnoid hemorrhage (SAH) across different centers and countries, it is unclear which factors contribute to such disparities. In this study, the authors performed a post hoc analysis of a large international database to evaluate the association between a country's socioeconomic indicators and patient outcome following aneurysmal SAH. An analysis was performed on a database of 3552 patients enrolled in studies of tirilazad mesylate for aneurysmal SAH from 1991 to 1997, which included 162 neurosurgical centers in North and Central America, Australia, Europe, and Africa. Two primary outcomes were assessed at 3 months after SAH: mortality and Glasgow Outcome Scale (GOS) score. The association between these outcomes, nation-level socioeconomic indicators (percapita gross domestic product [GDP], population-to-neurosurgeon ratio, and health care funding model), and patientlevel covariates were assessed using a hierarchical mixed-effects logistic regression analysis. Multiple previously identified patient-level covariates were significantly associated with increased mortality and worse neurological outcome, including age, intraventricular hemorrhage, and initial neurological grade. Among national-level covariates, higher per-capita GDP (p < 0.05) was associated with both reduced mortality and improved neurological outcome. A higher population-to-neurosurgeon ratio (p < 0.01), as well as fewer neurosurgical centers per population (p < 0.001), was also associated with better neurological outcome (p < 0.01). Health care funding model was not a significant predictor of either primary outcome. Higher per-capita gross GDP and population-to-neurosurgeon ratio were associated with improved outcome after aneurysmal SAH. The former result may speak to the availability of resources, while the latter may be a reflection of better outcomes with centralized care. Although patient clinical and radiographic phenotypes remain

  5. 807C/T polymorphism of platelet glycoprotein Ia gene is associated with cerebral hemorrhage in a Chinese population.

    PubMed

    Zeng, Yi; Zhang, Le; Hu, Zhiping; Yang, Qidong; Ma, Mingming; Liu, Baoqiong; Xia, Jian; Xu, Hongwei; Liu, Yunhai; Du, Xiaoping

    2016-08-01

    Platelet glycoprotein (GP) mediated the role of platelet in coagulation. Platelet GP Ia 807C/T is the only GP polymorphism associated with the expression levels of GP Ia/IIa (the platelet collagen receptor). Recently, the GP Ia 807C/T polymorphism has been reported to have no association with cerebral hemorrhage (CH) in two studies pertained to Caucasian populations. The purpose of this study is to evaluate the association between platelet GP Ia 807C/T polymorphism and CH in a Han Chinese population. We performed genotype analysis for platelet GP Ia 807C/T polymorphism in a case-control study involving 195 patients with CH and 116 age- and sex-matched controls. In contrast to previous reports, we found that the frequencies of GP Ia 807C/T T allele, CT and TT genotype were much higher in CH patients than in controls (33.9% vs. 22.8%, p = 0.004; 45.5% and 11.1% vs. 40.4% and 2.6%, p = 0.022). Logistic regression analysis revealed that the presence of GP Ia 807C/T C allele and CC genotype were both associated with a decreased risk of CH compared with T allele, CT and TT genotypes, respectively (adjusted odds ratio [OR] = 0.565, 95% CI: 0.384-0.887, p = 0.005; adjusted OR = 0.172, 95% CI: 0.043-0.639, p = 0.009; adjusted OR = 0.254, 95% CI: 0.085-0.961, p = 0.041, respectively). These findings indicated that platelet GP Ia 807C/T polymorphism could be a protective factor of CH in the Chinese population.

  6. Association between systemic inflammation and serum prostate-specific antigen in a healthy Korean population

    PubMed Central

    Yun, Jonghyun; Lee, Hyunyoung; Yang, Wonjae

    2017-01-01

    Objective Serum prostate-specific antigen (PSA) may be elevated in healthy men with systemic inflammation. We aimed to investigate the association between systemic inflammation markers and serum PSA in a healthy Korean population. Material and methods A cohort of 20,151 healthy native Korean men without prostate disease between the ages of 40 and 65 years who underwent medical checkups were studied from January 2007 to December 2013. Serum total PSA and serum C-reactive protein concentrations, neutrophil, lymphocyte, and platelet counts were determined. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were calculated. We checked the correlation between systemic inflammation markers and PSA. Results Data obtained from 18,800 healthy men were analyzed. The mean age of the study subjects was 50.72±7.62 years and the mean NLR was 1.764±0.804. Correlation analysis after adjustment for age and body mass index (BMI) revealed that neutrophil count (coefficient = 0.028, p value <0.001), and NLR (coefficient = 0.027, p value <0.001) correlated with PSA. Multivariate analysis using the full model revealed that age, neutrophil count and NLR were positively correlated with PSA (p<0.001, 0.001, and 0.043 respectively). Multivariate analysis using a stepwise model revealed that age, neutrophil count and NLR were positively correlated with PSA (p<0.001, 0.001, and 0.040, respectively) and BMI was negatively correlated with PSA (p<0.001). Conclusion Systemic inflammation markers are useful with a serum PSA in a healthy Korean population. NLR in particular is significantly associated with serum PSA. PMID:28861299

  7. Association of μ-Calpain and Calpastatin Polymorphisms with Meat Tenderness in a Brahman–Angus Population

    PubMed Central

    Leal-Gutiérrez, Joel D.; Elzo, Mauricio A.; Johnson, Dwain D.; Scheffler, Tracy L.; Scheffler, Jason M.; Mateescu, Raluca G.

    2018-01-01

    Autogenous proteolytic enzymes of the calpain family are implicated in myofibrillar protein degradation. As a result, the μ-calpain gene and its specific inhibitor, calpastatin, have been repeatedly investigated for their association with meat quality traits in cattle; however, no functional mutation has been identified for these two genes. The objectives of this study were: (1) to assess breed composition effect on tenderness; (2) to perform a linkage disequilibrium (LD) analysis in μ-calpain and calpastatin genes as well as an association analyses with tenderness; and (3) to analyze putative functional SNPs inside the significant LD block for an effect on tenderness. Tenderness measurements and genotypes for 16 SNPs in μ-calpain gene and 28 SNPs in calpastatin gene from 673 steers were analyzed. A bioinformatic analysis identified “putative functional SNPs” inside the associated LD block – polymorphisms able to produce a physical and/or chemical change in the DNA, mRNA, or translated protein in silico. Breed composition had a significant (P < 0.0001) effect on tenderness where animals with more than 80% Angus composition had the most tender meat. One 11-kb LD-block and three LD-blocks of 37, 17, and 14 kb in length were identified in the μ-calpain and calpastatin genes, respectively. Out of these, the LD-block 3 in calpastatin, tagged by SNPs located at 7-98566391 and 7-98581038, had a significant effect on tenderness with the TG-CG diplotype being approximately 1 kg more tender than the toughest diplotype, TG-CG. A total of 768 SNPs in the LD-block 3 of calpastatin were included in the bioinformatic analysis, and 28 markers were selected as putative functional SNPs inside the LD-block 3 of calpastatin; however, none of them were polymorphic in this population. Out of 15 initial polymorphisms segregating inside the LD-block 3 of calpastatin in this population, markers ARSUSMARC116, Cast5, rs730723459, and rs210861835 were found to be significantly

  8. Recapitulation of genome-wide association studies on pulse pressure and mean arterial pressure in the Korean population.

    PubMed

    Hong, Kyung-Won; Min, Haesook; Heo, Byeong-Mun; Joo, Seong Eun; Kim, Sung Soo; Kim, Yeonjung

    2012-06-01

    Increased pulse pressure (PP) and decreased mean arterial pressure (MAP) are strong prognostic predictors of adverse cardiovascular events. Recently, the International Consortium for Blood Pressure Genome-Wide Association Studies (ICBP-GWAS) reported eight loci that influenced PP and MAP. The ICBP-GWAS examined 51 cohorts--comprising 122 671 individuals of European ancestry--and identified eight SNPs: five that governed PP and three that controlled MAP. Six of these loci were novel. To replicate these newly identified loci and examine genetic architecture of PP and MAP between European and Asian populations, we conducted a meta-analysis of the eight SNPs combining data from ICBP and general population-based Korean cohorts. Two SNPs (rs13002573 (FIGN) and rs871606 (CHIC2)) for PP and two SNPs (rs1446468 (FIGN) and rs319690 (MAP4)) for MAP were replicated in Koreans. Although our GWAS only found moderate association, we believe that the findings promote us to propose that a similar genetic architecture governs PP and MAP in Asians and Europeans. However, further studies will be needed to confirm the possibility using other Asian population.

  9. Problematic alcohol use associates with sodium channel and clathrin linker 1 (SCLT1) in trauma-exposed populations.

    PubMed

    Almli, Lynn M; Lori, Adriana; Meyers, Jacquelyn L; Shin, Jaemin; Fani, Negar; Maihofer, Adam X; Nievergelt, Caroline M; Smith, Alicia K; Mercer, Kristina B; Kerley, Kimberly; Leveille, Jennifer M; Feng, Hao; Abu-Amara, Duna; Flory, Janine D; Yehuda, Rachel; Marmar, Charles R; Baker, Dewleen G; Bradley, Bekh; Koenen, Karestan C; Conneely, Karen N; Ressler, Kerry J

    2017-10-30

    Excessive alcohol use is extremely prevalent in the United States, particularly among trauma-exposed individuals. While several studies have examined genetic influences on alcohol use and related problems, this has not been studied in the context of trauma-exposed populations. We report results from a genome-wide association study of alcohol consumption and associated problems as measured by the alcohol use disorders identification test (AUDIT) in a trauma-exposed cohort. Results indicate a genome-wide significant association between total AUDIT score and rs1433375 [N = 1036, P = 2.61 × 10 -8 (dominant model), P = 7.76 × 10 -8 (additive model)], an intergenic single-nucleotide polymorphism located 323 kb upstream of the sodium channel and clathrin linker 1 (SCLT1) at 4q28. rs1433375 was also significant in a meta-analysis of two similar, but independent, cohorts (N = 1394, P = 0.0004), the Marine Resiliency Study and Systems Biology PTSD Biomarkers Consortium. Functional analysis indicated that rs1433375 was associated with SCLT1 gene expression and cortical-cerebellar functional connectivity measured via resting state functional magnetic resonance imaging. Together, findings suggest a role for sodium channel regulation and cerebellar functioning in alcohol use behavior. Identifying mechanisms underlying risk for problematic alcohol use in trauma-exposed populations is critical for future treatment and prevention efforts. © 2017 Society for the Study of Addiction.

  10. Psychosocial Factors Associated with Diet Quality in a Working Adult Population

    PubMed Central

    Dunbar, Sandra B.; Higgins, Melinda; Dai, Jun; Ziegler, Thomas R.; Frediani, Jennifer K.; Reilly, Carolyn; Brigham, Kenneth L.

    2014-01-01

    The associations between specific intra- and inter-personal psychosocial factors and dietary patterns were explored in a healthy, working adult population. Participants (N= 640) were enrolled in a prospective predictive health study and characterized by a mean age of 48(SD = 11) years, 67% women, and 30% minority. Baseline psychosocial measures of perceived stress, depressive symptoms, social support, and family functioning were examined for their relationships with three diet quality indices - AHEI, DASH, and the Mediterranean. Dietary intake was of moderate quality in this high income, well-educated, psychosocially healthy population. Social support was positively associated with better diet quality for all three indices (p< .01). Further research should focus on socio-environmental factors associated with diet quality. PMID:23408456

  11. Socioeconomic factors associated with drug consumption in prison population in Mexico

    PubMed Central

    2012-01-01

    Background Consumption of illegal drugs is a public health problem in Mexico, and the prison population is a vulnerable group with higher rates of prevalence than in the general population. The objective of this study was to determine the main socioeconomic variables associated with drug consumption in the prison population. Methods Utilizing data from the Second Incarcerated Population Survey carried out by the Centre of Research and Teaching of Economics (CIDE) in Mexico, a logistic model in two stages was developed. The first stage analyzed the determinants of habitual drug consumption by prisoners (prior to admittance into prisons), while the second stage of the model addressed drug consumption within prisons. Results Prevalence of drug consumption previous to incarceration was 28.5%, although once people were imprisoned this figure dropped to 7.4%. The characteristics that most heavily influenced against the possibility of habitual drug consumption prior to admittance to prison were: preparatory school or higher, being employed and having children; while the variables associated negatively were: male gender, childhood home shared with adults who consumed illegal drugs; abandoning childhood home; and having previous prison sentences. Once in prison, the negative conditions in there are associated with drug consumption. Conclusions Work and study during incarceration, in addition to being instruments for rehabilitation, seem to exert an important positive association against drug consumption. However, this correlation seems to be minimized in the face of negative conditions of the penal institution; thus, public policies are necessary to improve the prisoner's environment. PMID:22244315

  12. Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.

    PubMed

    Tan, Li-Jun; Zhu, Hu; He, Hao; Wu, Ke-Hao; Li, Jian; Chen, Xiang-Ding; Zhang, Ji-Gang; Shen, Hui; Tian, Qing; Krousel-Wood, Marie; Papasian, Christopher J; Bouchard, Claude; Pérusse, Louis; Deng, Hong-Wen

    2014-01-01

    Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10(-7) for BMI, 1.80×10(-6) for FM, and 5.29×10(-4) for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10(-3) to 4.94×10(-2)). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized

  13. Evidence for prospective associations among depression and obesity in population-based studies.

    PubMed

    Faith, M S; Butryn, M; Wadden, T A; Fabricatore, A; Nguyen, A M; Heymsfield, S B

    2011-05-01

    Obesity may lead to depression or be one of its consequences. We reviewed population-based studies in order to, first, identify the most commonly used research methods, and, second, to evaluate the strength of evidence for prospective associations among obesity and depression. We examined 25 studies, of which 10 tested 'obesity-to-depression' pathways, and 15 tested 'depression-to-obesity' pathways. Descriptive statistics summarized the frequency with which various measurements, designs and data analytic strategies were used. We tallied the number of studies that reported any vs. no statistically significant associations, and report on effect sizes, identified moderating variables within reports, and sought common findings across studies. Results indicated considerable methodological heterogeneity in the literature. Depression was assessed by clinical interview in 44% of studies, weight and height were directly measured in 32%, and only 12% used both. In total, 80% of the studies reported significant obesity-to-depression associations, with odds ratios generally in the range of 1.0 to 2.0, while only 53% of the studies reported significant depression-to-obesity associations. Sex was a common moderating variable. Thus, there was good evidence that obesity is prospectively associated with increased depression, with less consistent evidence that depression leads to obesity. Recommendations for future research regarding study samples, measurement and data analysis are provided. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.

  14. Deciphering Natural Allelic Variation in Switchgrass for Biomass Yield and Quality Using a Nested Association Mapping Population

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saha, Malay C.; Brummer, E. Charles; Kaeppler, Shawn

    Switchgrass (Panicum virgatum L.) is a C4 grass with high biomass yield potential and a model species for bioenergy feedstock development. Understanding the genetic basis of quantitative traits is essential to facilitate genome-enabled breeding programs. The nested association mapping (NAM) analysis combines the best features of both bi-parental and association analyses and can provide high power and high resolution in QTL detection and will ensure significant improvements in biomass yield and quality. To develop a NAM population of switchgrass, 15 highly diverse genotypes with specific characteristics were selected from a diversity panel and crossed to a recurrent parent, AP13, amore » genotype selected for whole genome sequencing and parent of a mapping population. Ten genotypes from each of the 15 F1 families were then chain crossed. Progenies form each family were randomly selected to develop the NAM population. The switchgrass NAM population consists of a total of 2000 genotypes from 15 families. All the progenies, founder parents, F1 parents (n=2350) were evaluated in replicated field trials at Ardmore, OK and Knoxville, TN. Phenotypic data on plant height, tillering ability, regrowth, flowering time, and biomass yield were collected. Dried biomass samples were also analyzed using prediction equations of NIRS at the Noble Foundation and for lignin content, S/G ratio, and sugar release characteristics at the NREL. Genomic shotgun sequencing of 15 switchgrass NAM founder parental genomes at JGI produced 28-66 Gb high-quality sequence data. Alignment of these sequences with the reference genome, AP13 (v3.0), revealed that up to 99% of the genomic sequences mapped to the reference genome. A total of 2,149 individuals from NAM populations were sequenced by exome capture and two sets of 15 SNP matrices (one for each family) were generated. QTL associated with important traits have been identified and verified in breeding populations. The QTL detected and their

  15. Phenotypic assessments of peanut nested association mapping (NAM) populations

    USDA-ARS?s Scientific Manuscript database

    Nested association mapping (NAM) is a valuable innovation and multi-parental mapping population strategy in peanut genetics which increases the power to map quantitative trait loci and assists in extending the gene pool of elite peanut lines. In the peanut research community, two structured mapping ...

  16. Indicator 1.08. Population levels of selected representative forest-associated species to describe genetic diversity

    Treesearch

    C. H. Sieg; S. M. Owen; C. H. Flather

    2011-01-01

    This indicator uses population trends of selected bird and tree species as a surrogate measure of genetic diversity. Population decreases, especially associated with small populations, can lead to decreases in genetic diversity, and contribute to increased risk of extinction. Many forest-associated species rely on some particular forest structure, vegetation...

  17. Population stress: A spatiotemporal analysis of population change and land development at the county level in the contiguous United States, 2001-2011.

    PubMed

    Chi, Guangqing; Ho, Hung Chak

    2018-01-01

    The past century has witnessed rapidly increasing population-land conflicts due to exponential population growth and its many consequences. Although the measures of population-land conflicts are many, there lacks a model that appropriately considers both the social and physical contexts of population-land conflicts. In this study we introduce the concept of population stress , which identifies areas with populations growing faster than the lands available for sustainable development. Specifically, population stress areas are identified by comparing population growth and land development as measured by land developability in the contiguous United States from 2001 to 2011. Our approach is based on a combination of spatial multicriteria analysis, zonal statistics, and spatiotemporal modeling. We found that the population growth of a county is associated with the decrease of land developability, along with the spatial influences of surrounding counties. The Midwest and the traditional "Deep South" counties would have less population stress with future land development, whereas the Southeast Coast, Washington State, Northern Texas, and the Southwest would face more stress due to population growth that is faster than the loss of suitable lands for development. The factors contributing to population stress may differ from place to place. Our population stress concept is useful and innovative for understanding population stress due to land development and can be applied to other regions as well as global research. It can act as a basis towards developing coherent sustainable land use policies. Coordination among local governments and across different levels of governments in the twenty-first century is a must for effective land use planning.

  18. GACD: Integrated Software for Genetic Analysis in Clonal F1 and Double Cross Populations.

    PubMed

    Zhang, Luyan; Meng, Lei; Wu, Wencheng; Wang, Jiankang

    2015-01-01

    Clonal species are common among plants. Clonal F1 progenies are derived from the hybridization between 2 heterozygous clones. In self- and cross-pollinated species, double crosses can be made from 4 inbred lines. A clonal F1 population can be viewed as a double cross population when the linkage phase is determined. The software package GACD (Genetic Analysis of Clonal F1 and Double cross) is freely available public software, capable of building high-density linkage maps and mapping quantitative trait loci (QTL) in clonal F1 and double cross populations. Three functionalities are integrated in GACD version 1.0: binning of redundant markers (BIN); linkage map construction (CDM); and QTL mapping (CDQ). Output of BIN can be directly used as input of CDM. After adding the phenotypic data, the output of CDM can be used as input of CDQ. Thus, GACD acts as a pipeline for genetic analysis. GACD and example datasets are freely available from www.isbreeding.net. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Prevalence of peripheral artery disease (PAD) and factors associated: An epidemiological analysis from the population-based Screening PRE-diabetes and type 2 DIAbetes (SPREDIA-2) study

    PubMed Central

    Cornejo del Río, V.; Mostaza, J.; Lahoz, C.; Sánchez-Arroyo, V.; Sabín, C.; López, S.; Patrón, P.; Fernández-García, P.; Fernández-Puntero, B.; Vicent, D.; Montesano-Sánchez, L.; García-Iglesias, F.; González-Alegre, T.; Estirado, E.; Laguna, F.; de Burgos-Lunar, C.; Gómez-Campelo, P.; Abanades-Herranz, J. C.; de Miguel-Yanes, J. M.; Salinero-Fort, M. A.

    2017-01-01

    Aim To describe the prevalence of Peripheral Artery Disease (PAD) in a random population sample and to evaluate its relationship with Mediterranean diet and with other potential cardiovascular risk factors such as serum uric acid and pulse pressure in individuals ranged 45 to 74 years. Methods Cross-sectional analysis of 1568 subjects (mean age 6.5 years, 43% males), randomly selected from the population. A fasting blood sample was obtained to determine glucose, lipids, and HbA1C levels. An oral glucose tolerance test was performed in non-diabetic subjects. PAD was evaluated by ankle–brachial index and/or having a prior diagnosis. Results PAD prevalence was 3.81% (95% CI, 2.97–4.87) for all participants. In men, PAD prevalence was significantly higher than in women [5.17% (95% CI, 3.74–7.11) vs. 2.78% (95% CI, 1.89–4.07); p = 0.014]. Serum uric acid in the upper quartile was associated with the highest odds ratio (OR) of PAD (for uric acid > 6.1 mg/dl, OR = 4.31; 95% CI, 1.49–12.44). The remaining variables more strongly associated with PAD were: Heart rate >90 bpm (OR = 4.16; 95%CI, 1.62–10.65), pulse pressure in the upper quartile (≥ 54 mmHg) (OR = 3.82; 95%CI, 1.50–9.71), adherence to Mediterranean diet (OR = 2.73; 95% CI, 1.48–5.04), and former smoker status (OR = 2.04; 95%CI, 1.00–4.16). Conclusions Our results show the existence of a low prevalence of peripheral artery disease in a population aged 45–74 years. Serum uric acid, pulse pressure and heart rate >90 bpm were strongly associated with peripheral artery disease. The direct association between Mediterranean diet and peripheral artery disease that we have found should be evaluated through a follow-up study under clinical practice conditions. PMID:29073236

  20. Genome-wide association study with the risk of schizophrenia in a Korean population.

    PubMed

    Kim, Lyoung Hyo; Park, Byung Lae; Cheong, Hyun Sub; Namgoong, Suhg; Kim, Ji On; Kim, Jeong-Hyun; Shin, Joong-Gon; Park, Chul Soo; Kim, Bong-Jo; Kim, Jae Won; Choi, Ihn-Geun; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

    2016-03-01

    Schizophrenia is regarded as a multifactorial and polygenic brain disorder that is attributed to different combinations of genetic and environmental risk factors. Recently, several genome-wide association studies (GWASs) of schizophrenia have identified numerous risk factors, but the replication results remain controversial and ambiguous. To identify schizophrenia susceptibility loci in the Korean population, we performed a GWAS using the Illumina HumanOmni1-Quad V1.0 Microarray. We genotyped 1,140,419 single nucleotide polymorphisms (SNPs) in 350 Korea schizophrenia patients and 700 control subjects, and approximately 620,001 autosomal SNPs were passed our quality control. In the case-control analysis, the rs9607195 A>G on intergenic area 250 kb away from the ISX gene and the rs12738007 A>G on the intron of the MECR gene were the most strongly associated SNPs with the risk of schizophrenia (P = 6.2 × 10(-8) , OR = 0.50 and P = 3.7 × 10(-7) , OR = 2.39, respectively). In subsequent fine-mapping analysis, 6 SNPs of MECR were genotyped with 310 schizophrenia patients and 604 control subjects. The association of the MECR rs12738007, a top ranked-SNP in GWAS, was replicated (P = 1.5 × 10(-2) , OR = 1.53 in fine mapping analysis, P = 1.5 × 10(-6) , OR = 1.90 in combined analysis). The identification of putative schizophrenia susceptibility loci could provide new insights into genetic factors related with schizophrenia and clues for the development of diagnosis strategies. © 2015 Wiley Periodicals, Inc.

  1. Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

    PubMed

    Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

    2018-05-07

    Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

  2. Factors associated with psychological distress or common mental disorders in migrant populations across the world.

    PubMed

    Jurado, Dolores; Alarcón, Renato D; Martínez-Ortega, José M; Mendieta-Marichal, Yaiza; Gutiérrez-Rojas, Luis; Gurpegui, Manuel

    We systematically review factors associated with the presence of psychological distress or common mental disorders in migrant populations. Articles published between January 2000 and December 2014 were reviewed and 85 applying multivariate statistical analysis were selected. Common mental disorders were significantly associated with socio-demographic and psychological characteristics, as observed in large epidemiological studies on general populations. The probability of common mental disorders occurrence differs significantly among migrant groups according to their region of origin. Moreover, traumatic events prior to migration, forced, unplanned, poorly planned or illegal migration, low level of acculturation, living alone or separated from family in the host country, lack of social support, perceived discrimination, and the length of migrants' residence in the host country all increase the likelihood of CMD. In contrast, language proficiency, family reunification, and perceived social support reduce such probability. Factors related with the risk of psychiatric morbidity among migrants should be taken into account to design preventive strategies. Copyright © 2016 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Personal contact with HIV-positive persons is associated with reduced HIV-related stigma: cross-sectional analysis of general population surveys from 26 countries in sub-Saharan Africa.

    PubMed

    Chan, Brian T; Tsai, Alexander C

    2017-01-11

    HIV-related stigma hampers treatment and prevention efforts worldwide. Effective interventions to counter HIV-related stigma are greatly needed. Although the "contact hypothesis" suggests that personal contact with persons living with HIV (PLHIV) may reduce stigmatizing attitudes in the general population, empirical evidence in support of this hypothesis is lacking. Our aim was to estimate the association between personal contact with PLHIV and HIV-related stigma among the general population of sub-Saharan Africa. Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 26 African countries between 2003 and 2008. We fitted multivariable logistic regression models with country-level fixed effects, specifying social distance as the dependent variable and personal contact with PLHIV as the primary explanatory variable of interest. We analyzed data from 206,717 women and 91,549 men living in 26 sub-Saharan African countries. We estimated a statistically significant negative association between personal contact with PLHIV and desires for social distance (adjusted odds ratio [AOR] = 0.80; p  < 0.001; 95% Confidence Interval [CI], 0.73-0.88). In a sensitivity analysis, a similar finding was obtained with a model that used a community-level variable for personal contact with PLHIV (AOR = 0.92; p  < 0.001; 95% CI, 0.89-0.95). Personal contact with PLHIV was associated with reduced desires for social distance among the general population of sub-Saharan Africa. More contact interventions should be developed and tested to reduce the stigma of HIV.

  4. Personal contact with HIV-positive persons is associated with reduced HIV-related stigma: cross-sectional analysis of general population surveys from 26 countries in sub-Saharan Africa

    PubMed Central

    Chan, Brian T; Tsai, Alexander C

    2017-01-01

    Abstract Introduction: HIV-related stigma hampers treatment and prevention efforts worldwide. Effective interventions to counter HIV-related stigma are greatly needed. Although the “contact hypothesis” suggests that personal contact with persons living with HIV (PLHIV) may reduce stigmatizing attitudes in the general population, empirical evidence in support of this hypothesis is lacking. Our aim was to estimate the association between personal contact with PLHIV and HIV-related stigma among the general population of sub-Saharan Africa. Methods: Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 26 African countries between 2003 and 2008. We fitted multivariable logistic regression models with country-level fixed effects, specifying social distance as the dependent variable and personal contact with PLHIV as the primary explanatory variable of interest. Results: We analyzed data from 206,717 women and 91,549 men living in 26 sub-Saharan African countries. We estimated a statistically significant negative association between personal contact with PLHIV and desires for social distance (adjusted odds ratio [AOR] = 0.80; p < 0.001; 95% Confidence Interval [CI], 0.73–0.88). In a sensitivity analysis, a similar finding was obtained with a model that used a community-level variable for personal contact with PLHIV (AOR = 0.92; p < 0.001; 95% CI, 0.89–0.95). Conclusions: Personal contact with PLHIV was associated with reduced desires for social distance among the general population of sub-Saharan Africa. More contact interventions should be developed and tested to reduce the stigma of HIV. PMID:28362067

  5. [Hygienic characteristics of the population's morbidity rate associated with iodine deficiency in the Republic of Mordovia].

    PubMed

    Blinov, D S; Chemova, N N; Balykova, O P; Liapina, S A; Chugunova, L A

    2015-01-01

    In the article there are presented the results of research on naturally conditioned insufficiency of trace elements, particularly iodine, in the Republic of Mordovia. Iodine deficiency disorders are referred to the most common non-infectious human pathology. According to WHO data, about two billion people on Earth live in conditions of in iodine deficiency. In the Russian Federation there are no areas in which the population would not be at risk for the development of iodine deficiency disorders. To these regions and the Republic of Mordovia is referred. The prevalence of diseases caused by iodine deficiency among the urban population accounted for 100-150, among rural--130-350. In some regions of endemic goiter rate reaches 800. Analysis of the morbidity rate of the population in the Republic of Mordovia, associated with the iodine deficiency, shows that in the structure of diseases related to micronutrient deficiency, by 2013 diffuse goiter plays a leading role, beingfollowed by a multi-node (endemic) goiter onward thyroiditis, subclinical hypothyroidism and hyperthyroidism. Thus, the analysis of indices of new cases of diseases associated with the iodine deficiency, allows to make the conclusion that diffuse goiter is the most significant pathology. In the structure of diseases related to the micronutrient deficiency, out of the most frequently detected iodine deficiency disorders, the greatest fraction are diffuse and multinodular goiter. The study was conducted with the support of the project, performed in the framework of the basic part of the State assignment (project 2859) and a RHSF grant.

  6. Fatty Acid Diversity is Not Associated with Neutral Genetic Diversity in Native Populations of the Biodiesel Plant Jatropha curcas L.

    PubMed

    Martínez-Díaz, Yesenia; González-Rodríguez, Antonio; Rico-Ponce, Héctor Rómulo; Rocha-Ramírez, Víctor; Ovando-Medina, Isidro; Espinosa-García, Francisco J

    2017-01-01

    Jatropha curcas L. (Euphorbiaceae) is a shrub native to Mexico and Central America, which produces seeds with a high oil content that can be converted to biodiesel. The genetic diversity of this plant has been widely studied, but it is not known whether the diversity of the seed oil chemical composition correlates with neutral genetic diversity. The total seed oil content, the diversity of profiles of fatty acids and phorbol esters were quantified, also, the genetic diversity obtained from simple sequence repeats was analyzed in native populations of J. curcas in Mexico. Using the fatty acids profiles, a discriminant analysis recognized three groups of individuals according to geographical origin. Bayesian assignment analysis revealed two genetic groups, while the genetic structure of the populations could not be explained by isolation-by-distance. Genetic and fatty acid profile data were not correlated based on Mantel test. Also, phorbol ester content and genetic diversity were not associated. Multiple linear regression analysis showed that total oil content was associated with altitude and seasonality of temperature. The content of unsaturated fatty acids was associated with altitude. Therefore, the cultivation planning of J. curcas should take into account chemical variation related to environmental factors. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  7. [Fenetic analysis of aboriginal and introduced sable (Martes zibellina) populations in Russia].

    PubMed

    Monakhov, V G

    2001-09-01

    Using standard and mulivariate statistic methods, an epigenetic character--foramina in fossa condyloidei inferior, FFCI--was studied in sable populations. This character was shown to be most frequent in southeastern populations of the species (Primorye and the Baikal region) while its distribution in the remaining part of the range was polyclinal. The expression of FFCI was directly associated with coat color and longitude, and inversely associated with skull size. This trend was broken by some western populations formed in the 1950s by introduction, which exhibited stable morphological differences with adjacent aboriginal sable populations. Most populations of the species exhibit differences in the manifestation of the character. Frequency of the FFCI manifestation can be used as an additional population characteristic, an associative diagnostic character that shows high discriminating capability in detecting phenogenetic relationships of intraspecific groups.

  8. Vulnerable Populations and the Association between Periodontal and Chronic Kidney Disease

    PubMed Central

    Plantinga, Laura C.; Crews, Deidra C.; Bibbins-Domingo, Kirsten; Saran, Rajiv; Heung, Michael; Patel, Priti R.; Burrows, Nilka Ríos; Ernst, Kristina L.; Powe, Neil R.

    2011-01-01

    Summary Background and objectives Recent studies suggest an overall association between chronic kidney disease (CKD) and periodontal disease, but it is unknown whether this association is similar across various subpopulations. Design, setting, participants, & measurements This study was a cross-sectional analysis of 2001 to 2004 National Health and Nutrition Examination Survey data. CKD was defined as a urinary albumin-to-creatinine ratio ≥30 mg/g or estimated GFR of 15 to 59 ml/min per 1.73 m2. Adjusted odds ratios were calculated using multivariable logistic regression with U.S. population-based weighting. Results These analyses included 6199 dentate adult participants (aged 21 to 75 years) with periodontal exams. The estimated prevalences of moderate/severe periodontal disease and CKD were 5.3% and 10.6%, respectively. Periodontal disease was associated with >2-fold higher risk of CKD that was moderately attenuated after adjustment for age, gender, race/ethnicity, tobacco use, hypertension, diabetes, educational attainment, poverty index ratio, and dental care use. There were no statistically significant interactions between periodontal disease and race/ethnicity, educational attainment, or poverty status. Less-than-recommended dental care use was associated with periodontal disease and CKD and was increasingly prevalent among nonwhites, lower educational attainment, and lower poverty status. Conclusions The association between periodontal disease and CKD is not significantly different among subgroups. However, because nonwhites, those with a lower educational level, and the poor less frequently report use of recommended dental care, the association between periodontal disease and kidney function over time may become stronger among these groups and warrants further investigation. PMID:21350109

  9. Population-Specific Haplotype Association of the Postsynaptic Density Gene DLG4 with Schizophrenia, in Family-Based Association Studies

    PubMed Central

    Balan, Shabeesh; Yamada, Kazuo; Hattori, Eiji; Iwayama, Yoshimi; Toyota, Tomoko; Ohnishi, Tetsuo; Maekawa, Motoko; Toyoshima, Manabu; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Yoshikawa, Takeo

    2013-01-01

    The post-synaptic density (PSD) of glutamatergic synapses harbors a multitude of proteins critical for maintaining synaptic dynamics. Alteration of protein expression levels in this matrix is a marked phenomenon of neuropsychiatric disorders including schizophrenia, where cognitive functions are impaired. To investigate the genetic relationship of genes expressed in the PSD with schizophrenia, a family-based association analysis of genetic variants in PSD genes such as DLG4, DLG1, PICK1 and MDM2, was performed, using Japanese samples (124 pedigrees, n = 376 subjects). Results showed a significant association of the rs17203281 variant from the DLG4 gene, with preferential transmission of the C allele (p = 0.02), although significance disappeared after correction for multiple testing. Replication analysis of this variant, found no association in a Chinese schizophrenia cohort (293 pedigrees, n = 1163 subjects) or in a Japanese case-control sample (n = 4182 subjects). The DLG4 expression levels between postmortem brain samples from schizophrenia patients showed no significant changes from controls. Interestingly, a five marker haplotype in DLG4, involving rs2242449, rs17203281, rs390200, rs222853 and rs222837, was enriched in a population specific manner, where the sequences A-C-C-C-A and G-C-C-C-A accumulated in Japanese (p = 0.0009) and Chinese (p = 0.0007) schizophrenia pedigree samples, respectively. However, this could not be replicated in case-control samples. None of the variants in other examined candidate genes showed any significant association in these samples. The current study highlights a putative role for DLG4 in schizophrenia pathogenesis, evidenced by haplotype association, and warrants further dense screening for variants within these haplotypes. PMID:23936182

  10. Association of NCOA3 polymorphisms with Dyslipidemia in the Chinese Han population.

    PubMed

    Yu, Mingxi; Gilbert, Siame; Li, Yong; Zhang, Huiping; Qiao, Yichun; Lu, Yuping; Tang, Yuan; Zhen, Qing; Cheng, Yi; Liu, Yawen

    2015-10-09

    Nuclear receptor coactivator-3 (NCOA3) is involved in various physiological processes. Emerging evidence from previous studies using animal models suggests that the NCOA3 gene (NCOA3) plays a critical role in lipid metabolism as well as adipogenesis and obesity. The present study aims to investigate the association between NCOA3 SNPs and dyslipidemia in the Chinese Han population. Five hundred and twenty-nine (529) Chinese Han subjects were recruited. Four tag SNPs (rs2425955G > T, rs6066394T > C, rs10485463C > G, and rs6094753G > A) in NCOA3, selected from the HapMap website, were genotyped using MALDI-TOF mass spectrometry. Data analysis was performed using SPSS 16.0, SNPStats and haploview 4.2. Four SNPs (rs2425955, rs6066394, rs10485463, and rs6094753) were associated with triglyceride levels. Except for SNP rs10485463, genotype distributions and allele frequencies of the other three NCOA3 SNPs (rs2425955, rs6066394, and rs6094753) were significantly different between hypertriglyceridemia subjects and normal group. Significant differences were also observed in allele frequencies and genotype distributions of SNP rs10485463 between low-HDL cholesterolemia subjects and normal group. Carriers of rs2425955 T allele had a lower risk of hypertriglyceridemia compared to GG genotype. Similar results were observed from rs6094753. Subjects with rs6066394 CT genotype had a lower risk of hypertriglyceridemia than those with the TT genotype; however, CC and TT genotypes showed no significant difference in the risk of hypertriglyceridemia. Similar results were found in the association between rs6066394 and hypercholesterolemia. The variant alleles of rs2425955, rs6066394 and rs6094753 were associated with a lower risk of hypertriglyceridemia compared with the wild-type alleles. The G allele of rs10485463 was associated with an increased risk of low-HDL cholesterolemia. In the log-additive model the association between rs2425955 and hypertriglyceridemia remained significant

  11. Tumourigenic canine osteosarcoma cell lines associated with frizzled-6 up-regulation and enhanced side population cell frequency.

    PubMed

    de Sá Rodrigues, L C; Holmes, K E; Thompson, V; Newton, M A; Stein, T J

    2017-03-01

    An increased serum alkaline phosphatase concentration is known to be associated with a negative prognosis in canine and human osteosarcoma. To expand upon previous studies regarding the biological relevance of increased serum alkaline phosphatase as a negative prognostic factor, xenogeneic heterotopic transplants were performed using six canine primary osteosarcoma cell lines generated from patients with differing serum alkaline phosphatase concentrations (three normal and three increased). Three of the six cell lines were capable of generating tumours and tumour formation was independent of the serum alkaline phosphatase status of the cell line. Microarray analysis identified 379 genes as being differentially expressed between the tumourigenic and non-tumourigenic cell lines. Frizzled-6 was upregulated to the greatest extent (7.78-fold) in tumourigenic cell lines compared with non-tumourigenic cell lines. Frizzled-6, a co-receptor for Wnt ligands has been associated with enhanced tumour-initiating cells and poor prognosis for other tumours. The increased expression of frizzled-6 was confirmed by quantitative reverse transcription polymerase chain reaction (QPCR) and Western blot analysis. Additionally, the tumourigenic cell lines also had an increase in the percentage of side population cells compared with non-tumourigenic cell lines (5.89% versus 1.58%, respectively). There were no differences in tumourigenicity, frizzled-6 or percentage of side population cells noted between osteosarcoma cell lines generated from patients of differing serum alkaline phosphatase concentration. However, to our knowledge this is the first study to identified frizzled-6 as a possible marker of osteosarcoma cell populations with enhanced tumourigenicity and side population cells. Future work will focus on defining the role of frizzled-6 in osteosarcoma tumourigenesis and tumour-initiating cells. © 2015 John Wiley & Sons Ltd.

  12. A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

    PubMed

    Weedon, Michael N; Clark, Vanessa J; Qian, Yudong; Ben-Shlomo, Yoav; Timpson, Nicholas; Ebrahim, Shah; Lawlor, Debbie A; Pembrey, Marcus E; Ring, Susan; Wilkin, Terry J; Voss, Linda D; Jeffery, Alison N; Metcalf, Brad; Ferrucci, Luigi; Corsi, Anna Maria; Murray, Anna; Melzer, David; Knight, Bridget; Shields, Bev; Smith, George Davey; Hattersley, Andrew T; Di Rienzo, Anna; Frayling, Tim M

    2006-12-01

    Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

  13. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence

    PubMed Central

    Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Smith, G D; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

    2016-01-01

    Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case–control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence. PMID:26239293

  14. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.

    PubMed

    Spain, S L; Pedroso, I; Kadeva, N; Miller, M B; Iacono, W G; McGue, M; Stergiakouli, E; Davey Smith, G; Putallaz, M; Lubinski, D; Meaburn, E L; Plomin, R; Simpson, M A

    2016-08-01

    Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. This study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1409 individuals drawn from the top 0.0003 (IQ >170) of the population distribution of intelligence and 3253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina HumanExome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (genome-wide complex trait analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (s.e. 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

  15. Associations of blood lead, cadmium, and mercury with estimated glomerular filtration rate in the Korean general population: Analysis of 2008-2010 Korean National Health and Nutrition Examination Survey data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Yangho; Lee, Byung-Kook, E-mail: bklee@sch.ac.kr

    Introduction: The objective of this study was to evaluate associations between blood lead, cadmium, and mercury levels with estimated glomerular filtration rate in a general population of South Korean adults. Methods: This was a cross-sectional study based on data obtained in the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2010). The final analytical sample consisted of 5924 participants. Estimated glomerular filtration rate (eGFR) was calculated using the MDRD Study equation as an indicator of glomerular function. Results: In multiple linear regression analysis of log2-transformed blood lead as a continuous variable on eGFR, after adjusting for covariates including cadmium andmore » mercury, the difference in eGFR levels associated with doubling of blood lead were -2.624 mL/min per 1.73 m Superscript-Two (95% CI: -3.803 to -1.445). In multiple linear regression analysis using quartiles of blood lead as the independent variable, the difference in eGFR levels comparing participants in the highest versus the lowest quartiles of blood lead was -3.835 mL/min per 1.73 m Superscript-Two (95% CI: -5.730 to -1.939). In a multiple linear regression analysis using blood cadmium and mercury, as continuous or categorical variables, as independent variables, neither metal was a significant predictor of eGFR. Odds ratios (ORs) and 95% CI values for reduced eGFR calculated for log2-transformed blood metals and quartiles of the three metals showed similar trends after adjustment for covariates. Discussion: In this large, representative sample of South Korean adults, elevated blood lead level was consistently associated with lower eGFR levels and with the prevalence of reduced eGFR even in blood lead levels below 10 {mu}g/dL. In conclusion, elevated blood lead level was associated with lower eGFR in a Korean general population, supporting the role of lead as a risk factor for chronic kidney disease.« less

  16. PCSK1 rs6232 Is Associated with Childhood and Adult Class III Obesity in the Mexican Population

    PubMed Central

    Villalobos-Comparán, Marisela; Villamil-Ramírez, Hugo; Villarreal-Molina, Teresa; Larrieta-Carrasco, Elena; León-Mimila, Paola; Romero-Hidalgo, Sandra; Jacobo-Albavera, Leonor; Liceaga-Fuentes, Adriana E.; Campos-Pérez, Francisco J.; López-Contreras, Blanca E.; Tusié-Luna, Teresa; del Río-Navarro, Blanca E.; Aguilar-Salinas, Carlos A.; Canizales-Quinteros, Samuel

    2012-01-01

    Background Common variants rs6232 and rs6235 in the PCSK1 gene have been associated with obesity in European populations. We aimed to evaluate the contribution of these variants to obesity and related traits in Mexican children and adults. Methodology/Principal Findings Rs6232 and rs6235 were genotyped in 2382 individuals, 1206 children and 1176 adults. Minor allele frequencies were 0.78% for rs6232 and 19.99% for rs6235. Rs6232 was significantly associated with childhood obesity and adult class III obesity (OR = 3.01 95%CI 1.64–5.53; P = 4×10−4 in the combined analysis). In addition, this SNP was significantly associated with lower fasting glucose levels (P = 0.01) and with increased insulin levels and HOMA-B (P = 0.05 and 0.01, respectively) only in non-obese children. In contrast, rs6235 showed no significant association with obesity or with glucose homeostasis parameters in any group. Conclusion/Significance Although rs6232 is rare in the Mexican population, it should be considered as an important risk factor for extreme forms of obesity. PMID:22737226

  17. Association of polymorphisms in survivin gene with the risk of hepatocellular carcinoma in Chinese han population: a case control study

    PubMed Central

    2012-01-01

    Background Survivin, one of the strongest apoptosis inhibitors, plays a critical role in the development and progression of hepatocellular carcinoma (HCC). By comparison, relatively little is known about the effect of survivin gene polymorphisms on HCC susceptibility. Our study aimed to investigate the association of survivin gene polymorphisms with the risk of HCC in Chinese han population. Methods A case-control study was conducted in Chinese han population consisting of 178 HCC cases and 196 cancer-free controls. Information on demographic data and related risk factors was collected for all subjects. Polymorphisms of the survivin gene, including three loci of rs8073069, rs9904341 and rs1042489, were selected and genotyped by a polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) technique. Association analysis of genotypes/alleles and haplotypes from these loci with the risk of HCC was conducted under different genetic models. Results Using univariate analysis of rs8073069, rs9904341 and rs1042489 under different genetic models, no statistically significant difference was found in genotype or allele distribution of HCC cases relative to the controls (P > 0.05). Linkage disequilibrium (LD) analysis showed that these loci were in LD. Multivariate logistic regression indicated that with no G-C-T haplotype as reference, the haplotype of G-C-T from these loci was associated with a lower risk for HCC under the recessive model (OR = 0.46, 95% confidence interval (CI): 0.24~0.90, P = 0.023). Both HBsAg+ and the medical history of viral hepatitis type B were risk factors for HCC. However, no statistically significant haplotype-environment interaction existed. Conclusions No association between rs8073069, rs9904341 or rs1042489 in survivin gene and the risk of HCC is found in Chinese han population, but rs8073069G-rs9904341C- rs1042489T is perhaps a protective haplotype for HCC. PMID:22214342

  18. Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.

    PubMed

    Fesinmeyer, Megan D; Meigs, James B; North, Kari E; Schumacher, Fredrick R; Bůžková, Petra; Franceschini, Nora; Haessler, Jeffrey; Goodloe, Robert; Spencer, Kylee L; Voruganti, Venkata Saroja; Howard, Barbara V; Jackson, Rebecca; Kolonel, Laurence N; Liu, Simin; Manson, JoAnn E; Monroe, Kristine R; Mukamal, Kenneth; Dilks, Holli H; Pendergrass, Sarah A; Nato, Andrew; Wan, Peggy; Wilkens, Lynne R; Le Marchand, Loic; Ambite, José Luis; Buyske, Steven; Florez, Jose C; Crawford, Dana C; Hindorff, Lucia A; Haiman, Christopher A; Peters, Ulrike; Pankow, James S

    2013-09-25

    Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.

  19. Population drinking and fatal injuries in Eastern Europe: a time-series analysis of six countries.

    PubMed

    Landberg, Jonas

    2010-01-01

    To estimate to what extent injury mortality rates in 6 Eastern European countries are affected by changes in population drinking during the post-war period. The analysis included injury mortality rates and per capita alcohol consumption in Russia, Belarus, Poland, Hungary, Bulgaria and the former Czechoslovakia. Total population and gender-specific models were estimated using auto regressive integrated moving average time-series modelling. The estimates for the total population were generally positive and significant. For Russia and Belarus, a 1-litre increase in per capita consumption was associated with an increase in injury mortality of 7.5 and 5.5 per 100,000 inhabitants, respectively. The estimates for the remaining countries ranged between 1.4 and 2.0. The gender-specific estimates displayed national variations similar to the total population estimates although the estimates for males were higher than for females in all countries. The results suggest that changes in per capita consumption have a significant impact on injury mortality in these countries, but the strength of the association tends to be stronger in countries where intoxication-oriented drinking is more common. Copyright 2009 S. Karger AG, Basel.

  20. Life-history strategies associated with local population variability confer regional stability.

    PubMed

    Pribil, Stanislav; Houlahan, Jeff E

    2003-07-07

    A widely held ecological tenet is that, at the local scale, populations of K-selected species (i.e. low fecundity, long lifespan and large body size) will be less variable than populations of r-selected species (i.e. high fecundity, short lifespan and small body size). We examined the relationship between long-term population trends and life-history attributes for 185 bird species in the Czech Republic and found that, at regional spatial scales and over moderate temporal scales (100-120 years), K-selected bird species were more likely to show both large increases and decreases in population size than r-selected species. We conclude that life-history attributes commonly associated with variable populations at the local scale, confer stability at the regional scale.

  1. Neighborhood deprivation is strongly associated with participation in a population-based health check.

    PubMed

    Bender, Anne Mette; Kawachi, Ichiro; Jørgensen, Torben; Pisinger, Charlotta

    2015-01-01

    We sought to examine whether neighborhood deprivation is associated with participation in a large population-based health check. Such analyses will help answer the question whether health checks, which are designed to meet the needs of residents in deprived neighborhoods, may increase participation and prove to be more effective in preventing disease. In Europe, no study has previously looked at the association between neighborhood deprivation and participation in a population-based health check. The study population comprised 12,768 persons invited for a health check including screening for ischemic heart disease and lifestyle counseling. The study population was randomly drawn from a population of 179,097 persons living in 73 neighborhoods in Denmark. Data on neighborhood deprivation (percentage with basic education, with low income and not in work) and individual socioeconomic position were retrieved from national administrative registers. Multilevel regression analyses with log links and binary distributions were conducted to obtain relative risks, intraclass correlation coefficients and proportional change in variance. Large differences between neighborhoods existed in both deprivation levels and neighborhood health check participation rate (mean 53%; range 35-84%). In multilevel analyses adjusted for age and sex, higher levels of all three indicators of neighborhood deprivation and a deprivation score were associated with lower participation in a dose-response fashion. Persons living in the most deprived neighborhoods had up to 37% decreased probability of participating compared to those living in the least deprived neighborhoods. Inclusion of individual socioeconomic position in the model attenuated the neighborhood deprivation coefficients, but all except for income deprivation remained statistically significant. Neighborhood deprivation was associated with participation in a population-based health check in a dose-response manner, in which increasing

  2. [Association between ABO blood groups and coronary heart disease in Chinese Guangxi Zhuang population].

    PubMed

    Shi, Ying; Lin, Yingzhong; Liu, Hairun; Ji, Qingwei; Lu, Zhihong; Lu, Zhengde; Xu, Nengwen; Yuan, Jun; Liu, Ling

    2015-09-01

    To investigate this association between ABO blood groups and coronary heart disease (CHD) in the Chinese Guangxi Zhuang population. From August 2010 to April 2013, we performed a case-control study in a Chinese Zhuang population, which included 1 024 CHD cases and 1 024 age and gender-matched non-CHD controls. The ABO blood groups and biological variables were measured by standard laboratory procedures. The Gensini score was used to evaluate the severity of coronary artery stenosis. Compared to non-CHD control group, CHD group had higher levels of fasting blood glucose ((6.71 ± 6.72) mmol/L vs. (4.98 ± 1.55) mmol/L, P < 0.001), LDL-C ((2.89 ± 1.18) mmol/L vs. (2.60 ± 1.05) mmol/L, P = 0.002) and CRP ((7.74 ± 7.32) mg/L vs. (2.93 ± 2.19)mg/L, P < 0.001) as well as higher proportion of history of hypertension (57.0% vs. 27.5%, P < 0.001), history of diabetes (29.6% vs. 9.6%, P < 0.001), family history of CHD (35.3% vs. 10.6%, P < 0.001) and smoking (51.0% vs. 38.2%, P < 0.001). Logistic analysis indicated that ABO blood groups were associated with CHD risk in the Chinese Zhuang population. Compared with group O, the group B individuals had a higher risk of CHD (OR = 2.33, 95% CI 1.88-2.90, P < 0.001), this result remained after adjustment for the conventional CHD risk factors (OR = 1.55, 95% CI 1.05-2.52, P = 0.047). In addition, there were significant differences of Gensini score between non-O subjects and group O subjects in the CHD group, and MACE at 1-year follow-up was similar between ABO blood groups of CHD individuals. ABO blood groups are associated with CHD risk in the Chinese Zhuang population.

  3. Associations between incident ischemic stroke events and stroke and cardiovascular disease-related genome-wide association studies single nucleotide polymorphisms in the Population Architecture Using Genomics and Epidemiology study.

    PubMed

    Carty, Cara L; Buzková, Petra; Fornage, Myriam; Franceschini, Nora; Cole, Shelley; Heiss, Gerardo; Hindorff, Lucia A; Howard, Barbara V; Mann, Sue; Martin, Lisa W; Zhang, Ying; Matise, Tara C; Prentice, Ross; Reiner, Alexander P; Kooperberg, Charles

    2012-04-01

    Genome-wide association studies (GWAS) have identified loci associated with ischemic stroke (IS) and cardiovascular disease (CVD) in European-descent individuals, but their replication in different populations has been largely unexplored. Nine single nucleotide polymorphisms (SNPs) selected from GWAS and meta-analyses of stroke, and 86 SNPs previously associated with myocardial infarction and CVD risk factors, including blood lipids (high density lipoprotein [HDL], low density lipoprotein [LDL], and triglycerides), type 2 diabetes, and body mass index (BMI), were investigated for associations with incident IS in European Americans (EA) N=26 276, African-Americans (AA) N=8970, and American Indians (AI) N=3570 from the Population Architecture using Genomics and Epidemiology Study. Ancestry-specific fixed effects meta-analysis with inverse variance weighting was used to combine study-specific log hazard ratios from Cox proportional hazards models. Two of 9 stroke SNPs (rs783396 and rs1804689) were significantly associated with [corrected] IS hazard in AA; none were significant in this large EA cohort. Of 73 CVD risk factor SNPs tested in EA, 2 (HDL and triglycerides SNPs) were associated with IS. In AA, SNPs associated with LDL, HDL, and BMI were significantly associated with IS (3 of 86 SNPs tested). Out of 58 SNPs tested in AI, 1 LDL SNP was significantly associated with IS. Our analyses showing lack of replication in spite of reasonable power for many stroke SNPs and differing results by ancestry highlight the need to follow up on GWAS findings and conduct genetic association studies in diverse populations. We found modest IS associations with BMI and lipids SNPs, though these findings require confirmation.

  4. A case control association study of ACE gene polymorphism (I/D) with hypertension in Punjabi population from Faisalabad, Pakistan.

    PubMed

    Hussain, Misbah; Awan, Fazli Rabbi; Gujjar, Amna; Hafeez, Shakir; Islam, Mehboob

    2018-01-01

    Angiotensin converting enzyme (ACE) is a key component of renin angiotensin aldosterone system. It converts angiotensin I to angiotensin II. Insertion/deletion (I/D) polymorphism of ACE gene is found associated with several complications. However, its association with hypertension and related metabolic diseases is still controversial. So, the aim of the present study was to check this association for Punjabi population from Faisalabad, Pakistan. For this purpose, blood samples (patients = 100, controls = 48) were collected and several biochemical parameters were measured. Genotyping for ACE (I/D) polymorphism was performed by polymerase chain reaction (PCR) assay. ID genotype is found prevalent in the studied population as 41% in control subjects and 61% in patients. Furthermore, chi-square analysis showed significant (p = 0.005) difference for genotypic frequencies between both groups. One-way ANOVA for association of II, ID, and DD genotypes with anthropometric, clinical, and biochemical parameters showed that in patient group, DD genotype is significantly (p = 0.041) associated with systolic blood pressure (SBP). Moreover, ID genotype is found associated with the presence of cardiovascular diseases. This study concludes that DD genotype is strongly associated with higher SBP in hypertensive patients.

  5. Ecological analysis of teen birth rates: association with community income and income inequality.

    PubMed

    Gold, R; Kawachi, I; Kennedy, B P; Lynch, J W; Connell, F A

    2001-09-01

    To examine whether per capita income and income inequality are independently associated with teen birth rate in populous U.S. counties. This study used 1990 U.S. Census data and National Center for Health Statistics birth data. Income inequality was measured with the 90:10 ratio, a ratio of percent of cumulative income held by the richest and poorest population deciles. Linear regression and analysis of variance were used to assess associations between county-level average income, income inequality, and teen birth rates among counties with population greater than 100,000. Among teens aged 15-17, income inequality and per capita income were independently associated with birth rate; the mean birth rate was 54 per 1,000 in counties with low income and high income inequality, and 19 per 1,000 in counties with high income and low inequality. Among older teens (aged 18-19) only per capita income was significantly associated with birth rate. Although teen childbearing is the result of individual behaviors, these findings suggest that community-level factors such as income and income inequality may contribute significantly to differences in teen birth rates.

  6. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

    PubMed

    Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

    2010-06-17

    There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and

  7. Dental caries experience and association to risk indicators of remote rural populations.

    PubMed

    Cook, Sean L; Martinez-Mier, E Angeles; Dean, Jeffrey A; Weddell, James A; Sanders, Brian J; Eggertsson, Hafsteinn; Ofner, Susan; Yoder, Karen

    2008-07-01

    Dental caries continues to be the most common infectious disease of childhood; however, it is no longer pandemic, but endemic in specific sectors of populations. Therefore, it is important to identify and target patients at risk of developing caries in order to develop specific preventive measures. This study aims to test dental caries risk indicators for significant associations with caries severity. Five separate, small, isolated rural villages in Mexico with varying degrees of caries prevalence were selected for this observational study. A total of 248 children were examined. Risk indicators were assessed via questionnaire and water and salt fluoride analysis. Caries severity was measured by the International Caries Detection and Assessment System (ICDAS-I). Prevalence of caries ranged from 95% to 100% for the five villages. Mean total DMFS (decayed, missing, or filled surfaces-permanent teeth) and dmfs (decayed, missing, or filled surfaces-primary teeth) scores ranged from 2.5 to 5.0 and from 11.3 to 16.9, respectively. Multivariable models showed age and drinking soda between meals to be significantly associated with DMFS, and drinking juice and being female were significantly associated with dmfs. DMFS and dmfs were high in each village, significantly different between villages, and associated with specific risk indicators.

  8. Association between Vitamin D level and/or deficiency, and systemic lupus erythematosus: a meta-analysis.

    PubMed

    Bae, Sang-Cheol; Lee, Young Ho

    2018-01-31

    This study aimed to evaluate the relationship between the level of 25-hydroxyvitamin D [25(OH)D] and systemic lupus erythematosus (SLE). We searched the PUBMED, EMBASE, and Cochrane databases and performed a meta-analysis examining the vitamin D level and/or deficiency in patients with SLE, compared with that in healthy controls. In total, 18 studies consisting of 1,083 patients with SLE and 1,273 controls were included. Vitamin D level was significantly lower in the SLE group than in the control group (standardized mean difference [SMD] = -0.938, 95% CI = -1.352 to -0.524, p = 9.0 × 10-6). Stratification by ethnicity showed a significantly decreased vitamin D level in the SLE group in the European and Arab populations (SMD = -1.485, 95% CI = -2.427 to -0.543, p = 0.002; SMD = -1.067, 95% CI = -1.251 to -0.883, p < 1.0 × 10-8), and an association tendency between decreased vitamin D level and SLE in the Asian population (SMD = -0.874, 95% CI = -2.073 to -0.324, p = 0.153). Subgroup analysis by sample size showed a significantly lower vitamin D level in the SLE group in small- (n ≤ 100) and large-sample (n > 100) populations (SMD = -1.008, 95% CI = -1.672 to -0.344, p = 0.003; SMD = -0.863, 95% CI = -1.444 to -0.293, p = 0.003). Meta-analysis revealed a significant association between SLE and vitamin D deficiency (RR = 2.321, 95% CI = 1.361-3.960, p = 0.002). Stratification by ethnicity showed a significant association between SLE and vitamin D deficiency in European and Arab populations (RR = 2.182, 95% CI = 1.024-4.648, p = 0.043; RR = 4.550, 95% CI = 3.471-5.965, p < 1.0 × 10-8). Our meta-analysis demonstrates that compared with controls, patients with SLE show significantly low serum levels of vitamin D, and that a deficiency of vitamin D is associated with SLE.

  9. Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population.

    PubMed

    Nabi, Gowher; Akhter, Naseem; Wahid, Mohd; Bhatia, Kanchan; Mandal, Raju Kumar; Dar, Sajad Ahmad; Jawed, Arshad; Haque, Shafiul

    2016-01-01

    The PTPN22 1858C/T polymorphism is associated with rheumatoid arthritis (RA). However, reports from the Asian populations are conflicting in nature and lacks consensus. The aim of our study was to evaluate the association between the PTPN22 1858C/T polymorphism and RA in Asian and Caucasian subjects by carrying out a meta-analysis of Asian and Caucasian data. A total of 27 205 RA cases and 27 677 controls were considered in the present meta-analysis involving eight Asian and 35 Caucasian studies. The pooled odds ratios (ORs) were performed for the allele, dominant, and recessive genetic model. No statistically significant association was found between the PTPN22 1858C/T polymorphism and risk of RA in Asian population (allele genetic model: OR = 1.217, 95% confidence interval (CI) = 0.99-1.496, p value 0.061; dominant genetic model: OR = 1.238, 95% CI = 0.982-1.562, p value 0.071; recessive genetic model: OR = 1.964, 95% CI = 0.678-5.693, p value 0.213). A significant association with risk of RA in Caucasian population suggesting that T-- allele does confer susceptibility to RA in this subgroup was observed (allele genetic model: OR = 1.638, 95% CI = 1.574-1.705, p value < 0.0001; dominant genetic model: OR = 1.67, 95% CI = 1.598-1.745, p value < 0.0001; recessive genetic model: OR = 2.65, 95% CI = 2.273-3.089, p value < 0.0001). The PTPN22 1858C/T polymorphism is not associated with RA risk in Asian populations. However, our meta-analysis confirms that the PTPN22 1858C/T polymorphism is associated with RA susceptibility in Caucasians.

  10. Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations.

    PubMed

    Hu, Yao; Li, Huaixing; Lu, Ling; Manichaikul, Ani; Zhu, Jingwen; Chen, Yii-Der I; Sun, Liang; Liang, Shuang; Siscovick, David S; Steffen, Lyn M; Tsai, Michael Y; Rich, Stephen S; Lemaitre, Rozenn N; Lin, Xu

    2016-03-15

    Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci (MYB, AGPAT4, DGAT2 and PPT2) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of MYB and AGPAT4 with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses (P = 4.15 × 10(-14) and 4.30 × 10(-12), respectively), while associations of DGAT2 with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of PPT2 with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses (P ≤ 0.003). We also confirmed previously reported loci including FADS1, NTAN1, NRBF2, ELOVL2 and GCKR. Different effect sizes in FADS1 and independent association signals in ELOVL2 were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. [Risk factors associated to diffuse gastric cancer and intestinal histological patterns in an adult population from Western Mexico].

    PubMed

    Delgado-Figueroa, Netzahualpilli; Casas-Junco, Paloma; Torres-Jasso, Juan Heriberto; Bustos-Carpinteyro, Andrea Rebeca; Santiago-Luna, Ernesto; Marín-Contreras, María Eugenia; Sánchez-López, Josefina Yoaly

    Gastric cancer (GC) is the third leading cause of cancer death worldwide, and is divided histologically in diffuse gastric cancer (DGC) and intestinal gastric cancer (IGC). Multiple risk factors have been associated with GC in different populations. The objective was to analyze the risk factors associated to DGC and IGC in a population from the western region of Mexico. The DGC (n = 27) and IGC (n = 26) cases, each matched by age and sex with a control group, were analyzed. Diet and lifestyle data were obtained by a questionnaire. Statistical analysis was performed with the software SPSSv18. The association of risk was calculated in odds ratio (OR); a value of p < 0.05 was considered significant. In the DGC group, the factors with significant OR values were: consumption of pork OR: 3.4 (1.11-10.4; p =0.032), smoking OR: 4.7 (1.5-15.0; p =0.007), green vegetables OR: 0.16 (0.03-0.83; p =0.029) and fruit OR: 0.28 (0.08-0.88; p =0.029). In the IGC group, the consumption of canned sardines was a significant risk factor OR: 4.07 (1.25-13.24; p =0.019). This work is the first to analyze the risk factors associated with GC in a population from western Mexico.

  12. Association between depression and periodontitis: a systematic review and meta-analysis.

    PubMed

    Araújo, Milena Moreira; Martins, Carolina Castro; Costa, Lidiane Cristina Machado; Cota, Luís Otávio Miranda; Faria, Rodrigo Lamounier Araújo Melo; Cunha, Fabiano Araújo; Costa, Fernando Oliveira

    2016-03-01

    The aim of this systematic review and meta-analysis was to assess the scientific evidence on the association between depression and periodontitis. An electronic search was conducted in three databases until October 2015 (PROSPERO-CRD42014006451). Hand searches and grey literature were also included. Search retrieved 423 potentially studies. Two independent reviewers selected the studies, extracted data and assessed risk bias through a modified version of Newcastle-Ottawa scale. Meta-analysis was performed for the presence/absence of periodontitis (dichotomic). Summary effect measures and odds ratio (OR) 95% CI were calculated. After selecting the studies, 15 were included in the systematic review (eight cross-sectional, six case-control and one cohort study). Six studies reported that depression was associated with periodontitis, whereas nine studies did not. The majority of studies had low risk of bias by methodological quality assessment. Meta-analysis of seven cross-sectional studies showed no significant association between depression and periodontitis (OR = 1.03, 95% CI = 0.75-1.41). Findings from the present systematic review showed a great heterogeneity among the studies and the summary effect measure of the meta-analysis cannot affirm an association between depression and periodontitis. Future studies with different designs in distinct populations should be conducted to investigate this association. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

    PubMed

    Ramos, Geovana Brotto; Salomão, Heloisa; Francio, Angela Schneider; Fava, Vinícius Medeiros; Werneck, Renata Iani; Mira, Marcelo Távora

    2016-08-01

    Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  14. Assessing population exposure for landslide risk analysis using dasymetric cartography

    NASA Astrophysics Data System (ADS)

    Garcia, Ricardo A. C.; Oliveira, Sergio C.; Zezere, Jose L.

    2015-04-01

    Exposed Population is a major topic that needs to be taken into account in a full landslide risk analysis. Usually, risk analysis is based on an accounting of inhabitants number or inhabitants density, applied over statistical or administrative terrain units, such as NUTS or parishes. However, this kind of approach may skew the obtained results underestimating the importance of population, mainly in territorial units with predominance of rural occupation. Furthermore, the landslide susceptibility scores calculated for each terrain unit are frequently more detailed and accurate than the location of the exposed population inside each territorial unit based on Census data. These drawbacks are not the ideal setting when landslide risk analysis is performed for urban management and emergency planning. Dasymetric cartography, which uses a parameter or set of parameters to restrict the spatial distribution of a particular phenomenon, is a methodology that may help to enhance the resolution of Census data and therefore to give a more realistic representation of the population distribution. Therefore, this work aims to map and to compare the population distribution based on a traditional approach (population per administrative terrain units) and based on dasymetric cartography (population by building). The study is developed in the Region North of Lisbon using 2011 population data and following three main steps: i) the landslide susceptibility assessment based on statistical models independently validated; ii) the evaluation of population distribution (absolute and density) for different administrative territorial units (Parishes and BGRI - the basic statistical unit in the Portuguese Census); and iii) the dasymetric population's cartography based on building areal weighting. Preliminary results show that in sparsely populated administrative units, population density differs more than two times depending on the application of the traditional approach or the dasymetric

  15. Neovascular age-related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population-based study.

    PubMed

    Hu, Chao-Chien; Lin, Herng-Ching; Sheu, Jau-Jiuan; Kao, Li-Ting

    2017-11-01

    This case-control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age-related macular degeneration (AMD) using a population-based data set in Taiwan. We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age- and sex-matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls. Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04-1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91-1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15-1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05-1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32-1.65) were significantly associated with AMD. This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  16. Short-term population-based and spatiotemporal nonlinear concentration-response associations between fine particulate matter and children's respiratory clinic visits

    NASA Astrophysics Data System (ADS)

    Yu, Hwa-Lung; Chien, Lung-Chang

    2014-05-01

    Advert health impacts associated with the PM2.5 exposure have been confirmed in mortality and cardiovascular diseases; however, findings of the influence of PM2.5 on respiratory diseases investigated among previous studies are still inconsistent. We investigated the short-term population-based associations between the respiratory clinic visits of children population and the PM2.5 exposure levels with considering both the spatiotemporal distributions of the ambient pollution and clinic visit data. We applied a spatiotemporal structured additive regression model to examine the concentration-response (C-R) association between daily children's respiratory clinic visits and PM2.5 concentrations. The analysis was performed separately on the four selected respiratory disease categories of the population-based dataset, obtained from Taiwan National Health Insurance database, covering the 41 districts in Taipei area during the period of 2005 to 2007. This study reveals a strong nonlinear C-R pattern that the PM2.5 increment can significantly affect respiratory health at PM2.5 concentration ≤ 18.17µg/m3 for both preschool children and schoolchildren. The elevated risks are especially present in the category of acute respiratory infections. PM2.5 increase is mostly non-significant to the more severe respiratory diseases, e.g., COPD and pneumonia, over the ranges of 8.85-92.45µg/m3. The significantly higher relative rate of respiratory clinic visit most likely concentrated at populated areas. We highlight the nonlinearity of the respiratory health impacts of PM2.5 on children's populations from the first study, to our knowledge, to investigate this population-based association. The strong nonlinearity can possibly cause the inconsistency of PM2.5 health impact assessments with linear assumptions.

  17. Risk of Dementia Associated with Elevated Plasma Homocysteine in a Latin American Population

    PubMed Central

    Chacón, Inara J.; Molero, Aldrín E.; Pino-Ramírez, Gloria; Luchsinger, José A.; Lee, Joseph H.; Maestre, Gladys E.

    2009-01-01

    The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia. PMID:20798752

  18. The association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease in a southern Chinese population.

    PubMed

    Zhang, Li; Wang, Jinxin; Che, Di; Wang, Yanfei; Rong, Xing; Pi, Lei; Xu, Yufen; Li, Wei; Huang, Ping; Chu, Maoping; Gu, Xiaoqiong

    2018-06-14

    miRNA-146a plays a critical role in innate immune and inflammatory responses. Kawasaki disease involves immune-mediated inflammatory responses, which lead to vascular endothelial injury. However, there has been no study on the association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease risk. We enrolled 532 Kawasaki disease patients and 623 healthy controls from a southern Chinese population, and the miRNA-146a rs2910164 C>G polymorphism was genotyped by the TaqMan method. There was no evidence that this polymorphism was associated with Kawasaki disease. Stratified analysis also showed no significant association. This study indicates that the miRNA-146a rs2910164 C>G polymorphism may not be associated with Kawasaki disease in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions. ©2018 The Author(s).

  19. Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study.

    PubMed

    Mir, Heshaam M; Stepanova, Maria; Afendy, Hena; Cable, Rebecca; Younossi, Zobair M

    2013-09-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11-1.76), OR = 1.39 (0.98-1.97), and OR = 2.17 (1.19-3.95); respectively)]. This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD.

  20. Association of Sleep Disorders with Nonalcoholic Fatty Liver Disease (NAFLD): A Population-based Study

    PubMed Central

    Mir, Heshaam M.; Stepanova, Maria; Afendy, Hena; Cable, Rebecca; Younossi, Zobair M.

    2013-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. In smaller studies, sleep apnea has been previously associated with NAFLD. The aim of this study was to assess the prevalence and independent associations of sleep disorders in patients with NAFLD using recent population-based data. Methods Three cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2010 were used. The diagnosis of NAFLD was established as elevated liver enzymes in the absence of all other causes of chronic liver disease. Sleep disorders were diagnosed using sleep disorder questionnaires completed by NHANES participants, and included self-reported history of sleep apnea, insomnia, and restless leg syndrome. The prevalence of sleep disorders was compared between those with and without NAFLD. Results A total of 10,541 adult NHANES participants with complete demographic, clinical, and laboratory data were included. Of those, 15.0% had NAFLD and 7.2% reported having sleep disorders. Of those with sleep disorders, 64.7% reported history of sleep apnea, 16.0% had history of insomnia, and 4.0% had restless leg syndrome. Individuals with NAFLD were more likely to be male (53.8% vs. 45.7%, P < 0.0001), obese (50.1% vs. 33.4%, P < 0.0001) and had higher prevalence of sleep disorders (9.1% vs. 6.9%, P = 0.0118). In multivariate analysis, having any sleep disorder, sleep apnea and insomnia were all independently associated with NAFLD [OR (95% CI) = 1.40 (1.11–1.76), OR = 1.39 (0.98–1.97), and OR = 2.17 (1.19–3.95); respectively)]. Conclusions This large population-based data suggests that NAFLD is associated with sleep disorders. Although the exact mechanism is unknown, this association is most likely through metabolic conditions associated with NAFLD. PMID:25755498

  1. MACROD2 gene associated with autistic-like traits in a general population sample.

    PubMed

    Jones, Rachel M; Cadby, Gemma; Blangero, John; Abraham, Lawrence J; Whitehouse, Andrew J O; Moses, Eric K

    2014-12-01

    There is now substantial evidence that autistic-like traits in the general population lie on a continuum, with clinical autism spectrum disorders (ASD) representing the extreme end of this distribution. In this study, we sought to evaluate five independently identified genetic associations with ASD with autistic-like traits in the general population. In the study cohort, clinical phenotype and genomewide association genotype data were obtained from the Western Australian Pregnancy Cohort (Raine) Study. The outcome measure used was the Autism Spectrum Quotient (AQ), a quantitative measure of autistic-like traits of individuals in the cohort. Total AQ scores were calculated for each individual, as well as scores for three subscales. Five candidate single nucleotide polymorphism (SNP) associations with ASD, reported in previously published genomewide association studies, were selected using a nominal cutoff value of P less than 1.0×10. We tested whether these five SNPs were associated with total AQ and the subscales, after adjustment for possible confounders. SNP rs4141463 located in the macro domain containing 2 (MACROD2) gene was significantly associated with the Communication/Mindreading subscale. No other SNP was significantly associated with total AQ or the subscales. The MACROD2 gene is a strong positional candidate risk factor for autistic-like traits in the general population.

  2. 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.

  3. Prevalence of ageing-associated cognitive decline in an elderly population.

    PubMed

    Hanninen, T; Koivisto, K; Reinikainen, K J; Helkala, E L; Soininen, H; Mykkänen, L; Laakso, M; Riekkinen, P J

    1996-05-01

    Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with ageing. Previously, we reported a high (38.4%) prevalence of age-associated memory impairment (AAMI) using the National Institute of Mental Health criteria in an elderly population. Recently, a work group of the International Psychogeriatric Association proposed criteria for 'ageing-associated cognitive decline' (AACD). The objective of this study was to evaluate the prevalence of AACD in an elderly population. We examined 403 randomly selected subjects (68-78 years of age) with tests of memory, cognitive processing, attention, verbal and visuoconstructive functions and with a structured questionnaire for health status and subjective complaints of cognitive decline. In all, 26.6% of the subjects (24.4% of women, 30. 1% or men) fulfilled the AACD criteria. The prevalence was slightly related to age and education. The rate was lowest in the oldest age of 75 - 78 years (20.5%) and highest in the age of 71 -74 years (30%). Subjects with less than 4 years of education had the lowest (14.3%) and subjects with more than 6 years of education had the highest rate (29.4%) for AACD. However, the differences between these subgroups were not statistically significant. These results suggest that the prevalence of AACD is lower than that of AAMI. As AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis, which takes into account age and education specific norms in its inclusion criteria, might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.

  4. Divergent population structure and climate associations of a chromosomal inversion polymorphism across the Mimulus guttatus species complex

    PubMed Central

    Oneal, Elen; Lowry, David B.; Wright, Kevin M.; Zhu, Zhirui; Willis, John H.

    2014-01-01

    Chromosomal rearrangement polymorphisms are common and increasingly found to be associated with adaptive ecological divergence and speciation. Rearrangements, such as inversions, reduce recombination in heterozygous individuals and thus can protect favourable allelic combinations at linked loci, facilitating their spread in the presence of gene flow. Recently, we identified a chromosomal inversion polymorphism that contributes to ecological adaptation and reproductive isolation between annual and perennial ecotypes of the yellow monkeyflower, Mimulus guttatus. Here we evaluate the population genetic structure of this inverted region in comparison with the collinear regions of the genome across the M. guttatus species complex. We tested whether annual and perennial M. guttatus exhibit different patterns of divergence for loci in the inverted and noninverted regions of the genome. We then evaluated whether there are contrasting climate associations with these genomic regions through redundancy analysis. We found that the inversion exhibits broadly different patterns of divergence among annual and perennial M. guttatus and is associated with environmental variation across population accessions. This study is the first widespread population genetic survey of the diversity of the M. guttatus species complex. Our findings contribute to a greater understanding of morphological, ecological, and genetic evolutionary divergence across this highly diverse group of closely related ecotypes and species. Finally, understanding species relationships among M. guttatus sp. has hitherto been stymied by accumulated evidence of substantial gene flow among populations as well as designated species. Nevertheless, our results shed light on these relationships and provide insight into adaptation in life history traits within the complex. PMID:24796267

  5. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    PubMed

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  6. A Study Assessing the Association of Glycated Hemoglobin A1C (HbA1C) Associated Variants with HbA1C, Chronic Kidney Disease and Diabetic Retinopathy in Populations of Asian Ancestry

    PubMed Central

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L.; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study. PMID:24244560

  7. Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

    PubMed

    Bae, Joon Seol; Kim, Jason Yongha; Park, Byung-Lae; Kim, Jeong-Hyun; Kim, Bomi; Park, Chul Soo; Kim, Bong-Jo; Lee, Cheol-Soon; Lee, Migyung; Choi, Woo Hyuk; Shin, Tae-Min; Hwang, Jaeuk; Shin, Hyoung Doo; Woo, Sung-Il

    2014-10-01

    Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

  8. Population Structure of Xylella fastidiosa Associated with Almond Leaf Scorch Disease in the San Joaquin Valley of California.

    PubMed

    Lin, Hong; Islam, Md Sajedul; Cabrera-La Rosa, Juan C; Civerolo, Edwin L; Groves, Russell L

    2015-06-01

    Xylella fastidiosa causes disease in many commercial crops, including almond leaf scorch (ALS) disease in susceptible almond (Prunus dulcis). In this study, genetic diversity and population structure of X. fastidiosa associated with ALS disease were evaluated. Isolates obtained from two almond orchards in Fresno and Kern County in the San Joaquin Valley of California were analyzed for two successive years. Multilocus simple-sequence repeat (SSR) analysis revealed two major genetic clusters that were associated with two host cultivars, 'Sonora' and 'Nonpareil', respectively, regardless of the year of study or location of the orchard. These relationships suggest that host cultivar selection and adaptation are major driving forces shaping ALS X. fastidiosa population structure in the San Joaquin Valley. This finding will provide insight into understanding pathogen adaptation and host selection in the context of ALS disease dynamics.

  9. Genome-Wide association study identifies candidate genes for Parkinson's disease in an Ashkenazi Jewish population

    PubMed Central

    2011-01-01

    Background To date, nine Parkinson disease (PD) genome-wide association studies in North American, European and Asian populations have been published. The majority of studies have confirmed the association of the previously identified genetic risk factors, SNCA and MAPT, and two studies have identified three new PD susceptibility loci/genes (PARK16, BST1 and HLA-DRB5). In a recent meta-analysis of datasets from five of the published PD GWAS an additional 6 novel candidate genes (SYT11, ACMSD, STK39, MCCC1/LAMP3, GAK and CCDC62/HIP1R) were identified. Collectively the associations identified in these GWAS account for only a small proportion of the estimated total heritability of PD suggesting that an 'unknown' component of the genetic architecture of PD remains to be identified. Methods We applied a GWAS approach to a relatively homogeneous Ashkenazi Jewish (AJ) population from New York to search for both 'rare' and 'common' genetic variants that confer risk of PD by examining any SNPs with allele frequencies exceeding 2%. We have focused on a genetic isolate, the AJ population, as a discovery dataset since this cohort has a higher sharing of genetic background and historically experienced a significant bottleneck. We also conducted a replication study using two publicly available datasets from dbGaP. The joint analysis dataset had a combined sample size of 2,050 cases and 1,836 controls. Results We identified the top 57 SNPs showing the strongest evidence of association in the AJ dataset (p < 9.9 × 10-5). Six SNPs located within gene regions had positive signals in at least one other independent dbGaP dataset: LOC100505836 (Chr3p24), LOC153328/SLC25A48 (Chr5q31.1), UNC13B (9p13.3), SLCO3A1(15q26.1), WNT3(17q21.3) and NSF (17q21.3). We also replicated published associations for the gene regions SNCA (Chr4q21; rs3775442, p = 0.037), PARK16 (Chr1q32.1; rs823114 (NUCKS1), p = 6.12 × 10-4), BST1 (Chr4p15; rs12502586, p = 0.027), STK39 (Chr2q24.3; rs3754775, p = 0

  10. Hypercontrols in genotype-phenotype analysis reveal ancestral haplotypes associated with essential hypertension.

    PubMed

    Balam-Ortiz, Eros; Esquivel-Villarreal, Adolfo; Huerta-Hernandez, David; Fernandez-Lopez, Juan Carlos; Alfaro-Ruiz, Luis; Muñoz-Monroy, Omar; Gutierrez, Ruth; Figueroa-Genis, Enrique; Carrillo, Karol; Elizalde, Adela; Hidalgo, Alfredo; Rodriguez, Mauricio; Urushihara, Maki; Kobori, Hiroyuki; Jimenez-Sanchez, Gerardo

    2012-04-01

    The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ(2)=23.9; P=0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ(2)=8.1; P=0.004) and H5 (χ(2)=5.1; P=0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as "superalleles."

  11. Hypercontrols in Genotype-Phenotype Analysis Reveal Ancestral Haplotypes Associated With Essential Hypertension

    PubMed Central

    Balam-Ortiz, Eros; Esquivel-Villarreal, Adolfo; Huerta-Hernandez, David; Fernandez-Lopez, Juan Carlos; Alfaro-Ruiz, Luis; Muñoz-Monroy, Omar; Gutierrez, Ruth; Figueroa-Genis, Enrique; Carrillo, Karol; Elizalde, Adela; Hidalgo, Alfredo; Rodriguez, Mauricio; Urushihara, Maki; Kobori, Hiroyuki; Jimenez-Sanchez, Gerardo

    2012-01-01

    The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ2 = 23.9; P = 0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8–4.9; P = 0.000006) in the recessive model. Two polymorphisms, A-20C (P = 0.003) and C3389T (P = 0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ2 = 8.1; P = 0.004) and H5 (χ2 = 5.1; P = 0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as “superalleles.” PMID:22371359

  12. Identifying the association between interleukin-6 and lichen planus: A meta-analysis.

    PubMed

    Yin, Meng; Li, Guifeng; Song, Hui; Lin, Song

    2017-05-01

    Numerous studies have examined the association between interleukin-6 and the pathogenesis of lichen planus (LP)/oral LP (OLP) in various populations; however, there is a lack of systematic analysis. The aim of the present study was to assess this association more precisely, thus a meta-analysis was performed. Case-control studies, which were published up to December 2015, were obtained from PubMed, Embase and the China National Knowledge Infrastructure databases. Data were extracted and pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Ultimately, eight studies were included, comprising 299 LP/OLP cases and 231 control subjects. Overall, the pooled MD for IL-6 was 16.24 (95% CI, 9.84-22.64; I 2 =99% for heterogeneity). In the subgroup analysis by ethnicity, a significant increase of the IL-6 expression level was identified among Asian individuals, but not in Caucasian individuals. Thus, IL-6 may be significant in the pathogenesis of LP. However, further studies are required to validate these associations.

  13. Saturated fat intake modulates the association between a genetic risk score of obesity and BMI in two US populations

    PubMed Central

    Casas-Agustench, Patricia; Arnett, Donna K.; Smith, Caren E.; Lai, Chao-Qiang; Parnell, Laurence D.; Borecki, Ingrid B.; Frazier-Wood, Alexis C.; Allison, Matthew; Chen, Yii-Der Ida; Taylor, Kent D.; Rich, Stephen S.; Rotter, Jerome I.; Lee, Yu-Chi; Ordovás, José M.

    2014-01-01

    Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and BMI in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake and to replicate findings in Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 US Caucasian participants from GOLDN and 2035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005, 0.018, and <0.001 in GOLDN, MESA and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two US populations. Although to determine the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs. PMID:24794412

  14. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson's disease susceptibility in Chinese Han population.

    PubMed

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson's disease (PD) susceptibility in Chinese Han population. The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ(2) test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association.

  15. Association between serum ferritin and glaucoma in the South Korean population.

    PubMed

    Lin, Shuai-Chun; Wang, Sophia Y; Yoo, Chungkwon; Singh, Kuldev; Lin, Shan C

    2014-12-01

    Evidence suggests that altered iron metabolism may be associated with oxidative damage to several organ systems, including the eye. Supplementary iron consumption is also associated with greater odds of self-reported glaucoma. To investigate the association between serum ferritin level and the likelihood of a glaucoma diagnosis in a cross-sectional, population-based study. Data were collected from 17,476 participants in the first and second years of the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional study of the South Korean population conducted from January 1, 2010, through December 31, 2011. Data pertaining to the serum ferritin level were aggregated and divided into quartiles. Demographic, comorbidity, and health-related behavior information was obtained via interview. The presence or absence of glaucoma. The definition of glaucoma was based on criteria established by the International Society of Geographical and Epidemiological Ophthalmology. Participants whose serum ferritin level was greater than 61 ng/mL (to convert to picomoles per liter, multiply by 2.247) had significantly higher odds of a glaucoma diagnosis when compared with those with a level less than 31 ng/mL, after adjustment for potential confounders (ferritin levels of 31-61 ng/mL: odds ratio [OR], 1.17; 95% CI, 0.84-1.62; ferritin levels of 62-112 ng/mL: OR, 1.60; 95% CI, 1.16-2.20; and ferritin levels of 113-3018 ng/mL: OR, 1.89; 95% CI, 1.32-2.72). Our study reveals that a higher serum ferritin level was associated with greater odds of glaucoma in a representative sample of the South Korean population, even at levels normally observed in the general population. This novel finding may help elucidate the pathogenesis and lead to novel therapeutic approaches for glaucomatous disease.

  16. Sugar cane manufacturing is associated with tuberculosis in an indigenous population in Brazil.

    PubMed

    Sacchi, Flávia Patussi Correia; Croda, Mariana Garcia; Estevan, Anderson Oliveira; Ko, Albert I; Croda, Julio

    2013-03-01

    Tuberculosis (TB) remains one of the leading causes of morbidity and mortality among indigenous peoples in Brazil, and identifying the risk factors for TB in this population secondary to specific epidemiological conditions is essential for recommending interventions aimed at disease control. This case-control study was conducted with an indigenous population between June 2009 and August 2011 in Dourados, Brazil. Tuberculosis cases reported to the national disease surveillance programme were paired with two control cases matched by age and geographic location. There were 63 cases included in this study, and the annual incidence of TB in the indigenous communities examined was 222 (95% CI, 148-321) per 100 000 inhabitants. The multivariate analysis demonstrated that the variables associated with TB infection included male gender (OR 2.6; 95% CI 1.3-5.3), not owning a home (OR 3.4; 95% CI 1.2-10.1), illiteracy (OR 2.4; 95% CI 1.1-5.0), TB contact (OR 2.4; 95% CI 1.2-4.8) and work performed in a sugar cane factory (OR 6.8; 95% CI 1.2-36.9). There is a potential relationship between exposure to sugar cane manufacturing processes and tuberculosis infection among indigenous populations.

  17. Population assessment of tropical tuna based on their associative behavior around floating objects.

    PubMed

    Capello, M; Deneubourg, J L; Robert, M; Holland, K N; Schaefer, K M; Dagorn, L

    2016-11-03

    Estimating the abundance of pelagic fish species is a challenging task, due to their vast and remote habitat. Despite the development of satellite, archival and acoustic tagging techniques that allow the tracking of marine animals in their natural environments, these technologies have so far been underutilized in developing abundance estimations. We developed a new method for estimating the abundance of tropical tuna that employs these technologies and exploits the aggregative behavior of tuna around floating objects (FADs). We provided estimates of abundance indices based on a simulated set of tagged fish and studied the sensitivity of our method to different association dynamics, FAD numbers, population sizes and heterogeneities of the FAD-array. Taking the case study of yellowfin tuna (Thunnus albacares) acoustically-tagged in Hawaii, we implemented our approach on field data and derived for the first time the ratio between the associated and the total population. With more extensive and long-term monitoring of FAD-associated tunas and good estimates of the numbers of fish at FADs, our method could provide fisheries-independent estimates of populations of tropical tuna. The same approach can be applied to obtain population assessments for any marine and terrestrial species that display associative behavior and from which behavioral data have been acquired using acoustic, archival or satellite tags.

  18. Inflammation but not dietary macronutrients insufficiency associated with the malnutrition-inflammation score in hemodialysis population.

    PubMed

    Chen, Jie; Peng, Hongquan; Xiao, Long; Zhang, Kun; Yuan, Zhimin; Chen, Jianping; Wang, Zhiyu; Wang, Jingfeng; Huang, Hui

    2013-01-01

    Malnutrition is associated with increased risk of mortality in hemodialysis patients. And insufficient dietary intake is the common cause for malnutrition. So, in order to survey the dietary intake of hemodialysis patients and study the relationship between the dietary feature and nutritional status, a cross-sectional study was performed. 75 hemodialysis patients from South China participated in the dietary intake survey and nutrition assessment. A three-day diet diary record was used to estimate the major dietary macronutrients. Nutritional status was assessed by malnutrition-inflammation score (MIS) in addition to several related anthropometric measurements. Serum albumin, transferrin, and high-sensitivity C-reactive protein (CRP) were measured. Receiver operating characteristic (ROC) curve analysis was used to quantify the assessing value of independent parameters for nutritional status. The results showed that 48% patients were malnourished according to the MIS. The malnourished patients had a lower body mass index (BMI), fat mass (FM), albumin and a higher level of CRP, compared with normal nourished patients (P < 0.05). However, no significant differences of macronutrients (calories, protein, fat, carbohydrates, etc) were found between the two nutrition groups (P > 0.05). The multivariate regression analysis showed that the major macronutrients had no significant association with MIS (P > 0.05). In conclusion, malnutrition is very common in South China hemodialysis population and these data indicated that inflammation but not dietary macronutrients insufficiency might be the candidate cause for malnutrition in hemodialysis population.

  19. Inflammation but Not Dietary Macronutrients Insufficiency Associated with the Malnutrition-Inflammation Score in Hemodialysis Population

    PubMed Central

    Zhang, Kun; Yuan, Zhimin; Chen, Jianping; Wang, Zhiyu; Wang, Jingfeng; Huang, Hui

    2013-01-01

    Malnutrition is associated with increased risk of mortality in hemodialysis patients. And insufficient dietary intake is the common cause for malnutrition. So, in order to survey the dietary intake of hemodialysis patients and study the relationship between the dietary feature and nutritional status, a cross-sectional study was performed. 75 hemodialysis patients from South China participated in the dietary intake survey and nutrition assessment. A three-day diet diary record was used to estimate the major dietary macronutrients. Nutritional status was assessed by malnutrition-inflammation score (MIS) in addition to several related anthropometric measurements. Serum albumin, transferrin, and high-sensitivity C-reactive protein (CRP) were measured. Receiver operating characteristic (ROC) curve analysis was used to quantify the assessing value of independent parameters for nutritional status. The results showed that 48% patients were malnourished according to the MIS. The malnourished patients had a lower body mass index (BMI), fat mass (FM), albumin and a higher level of CRP, compared with normal nourished patients (P < 0.05). However, no significant differences of macronutrients (calories, protein, fat, carbohydrates, etc) were found between the two nutrition groups (P > 0.05). The multivariate regression analysis showed that the major macronutrients had no significant association with MIS (P > 0.05). In conclusion, malnutrition is very common in South China hemodialysis population and these data indicated that inflammation but not dietary macronutrients insufficiency might be the candidate cause for malnutrition in hemodialysis population. PMID:24349471

  20. A Comparative Analysis of the Validity of US State- and County-Level Social Capital Measures and Their Associations with Population Health

    PubMed Central

    Lee, Chul-joo; Kim, Daniel

    2014-01-01

    The goals of this study were to validate a number of available collective social capital measures at the U.S. state and county levels, and to examine the relative extent to which these social capital measures are associated with population health outcomes. Measures of social capital at the U.S. state level included aggregate indices based on the Annenberg National Health Communication Survey (ANHCS) and the Behavioral Risk Factor Surveillance System (BRFSS), Petris Social Capital Index (PSCI), Putnam’s index, and Kim et al.’s scales. County-level measures consisted of Rupasingha et al.’s social capital index (RGFI) and a BRFSS-derived measure. These measures, except for the PSCI, showed evidence of acceptable validity. Moreover, we observed differences across the social capital measures in their associations with population health outcomes. The implications of the findings for future research in this area are discussed. PMID:25574069

  1. A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

    PubMed

    Marzec, Jacek; Mao, Xueying; Li, Meiling; Wang, Meilin; Feng, Ninghan; Gou, Xin; Wang, Guomin; Sun, Zan; Xu, Jianfeng; Xu, Hua; Zhang, Xiaoping; Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F; Chelala, Claude; Al Olama, Ali Amin; Eeles, Rosalind A; Zhang, Hongwei; Lu, Yong-Jie

    2016-04-19

    Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.

  2. Association of Serum Thyrotropin with Anthropometric Markers of Obesity in the General Population.

    PubMed

    Tiller, Daniel; Ittermann, Till; Greiser, Karin H; Meisinger, Christa; Agger, Carsten; Hofman, Albert; Thuesen, Betina; Linneberg, Allan; Peeters, Robin; Franco, Oscar; Heier, Margit; Kluttig, Alexander; Werdan, Karl; Stricker, Bruno; Schipf, Sabine; Markus, Marcello; Dörr, Marcus; Völzke, Henry; Haerting, Johannes

    2016-09-01

    Except from associations study with body weight, there are few longitudinal data regarding the association between thyroid function and anthropometric measurements such as waist circumference, waist-to-hip ratio, or waist-to height ratio. This study aimed to investigate the association of thyrotropin (TSH) at baseline with changes in different anthropometric markers between baseline and follow-up in the general population. Data were used from four population-based longitudinal cohort studies and one population-based cross-sectional study. A total of 16,902 (8204 males) subjects aged 20-95 years from the general population were studied. Body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Multivariable median regression models were calculated adjusting for the following covariates: age, sex, baseline value of the respective anthropometric marker, smoking status, follow-up-time period, and study site. In cross-sectional analyses, serum TSH within the reference range was positively associated with waist circumference (β = 0.94 cm [confidence interval (CI) 0.56-1.32]) and waist-to-height-ratio (β = 0.029 [CI 0.017-0.042]). These associations were also present for the full range of TSH. In the longitudinal analyses, serum TSH at baseline was inversely associated with a five-year change of all considered anthropometric measures within the prior defined study-specific reference range, as well as in the full range of serum TSH. High TSH serum levels were positively associated with current anthropometric markers, even in the study-specific reference ranges. In contrast, high TSH serum levels were associated with decreased anthropometric markers over a time span of approximately five years. Further research is needed to determine possible clinical implications as well as public health consequences of these findings.

  3. Genome-wide analysis of epistasis in body mass index using multiple human populations.

    PubMed

    Wei, Wen-Hua; Hemani, Gib; Gyenesei, Attila; Vitart, Veronique; Navarro, Pau; Hayward, Caroline; Cabrera, Claudia P; Huffman, Jennifer E; Knott, Sara A; Hicks, Andrew A; Rudan, Igor; Pramstaller, Peter P; Wild, Sarah H; Wilson, James F; Campbell, Harry; Hastie, Nicholas D; Wright, Alan F; Haley, Chris S

    2012-08-01

    We surveyed gene-gene interactions (epistasis) in human body mass index (BMI) in four European populations (n<1200) via exhaustive pair-wise genome scans where interactions were computed as F ratios by testing a linear regression model fitting two single-nucleotide polymorphisms (SNPs) with interactions against the one without. Before the association tests, BMI was corrected for sex and age, normalised and adjusted for relatedness. Neither single SNPs nor SNP interactions were genome-wide significant in either cohort based on the consensus threshold (P=5.0E-08) and a Bonferroni corrected threshold (P=1.1E-12), respectively. Next we compared sub genome-wide significant SNP interactions (P<5.0E-08) across cohorts to identify common epistatic signals, where SNPs were annotated to genes to test for gene ontology (GO) enrichment. Among the epistatic genes contributing to the commonly enriched GO terms, 19 were shared across study cohorts of which 15 are previously published genome-wide association loci, including CDH13 (cadherin 13) associated with height and SORCS2 (sortilin-related VPS10 domain containing receptor 2) associated with circulating insulin-like growth factor 1 and binding protein 3. Interactions between the 19 shared epistatic genes and those involving BMI candidate loci (P<5.0E-08) were tested across cohorts and found eight replicated at the SNP level (P<0.05) in at least one cohort, which were further tested and showed limited replication in a separate European population (n>5000). We conclude that genome-wide analysis of epistasis in multiple populations is an effective approach to provide new insights into the genetic regulation of BMI but requires additional efforts to confirm the findings.

  4. Genetic Structure, Linkage Disequilibrium and Association Mapping of Verticillium Wilt Resistance in Elite Cotton (Gossypium hirsutum L.) Germplasm Population

    PubMed Central

    Zhao, Yunlei; Wang, Hongmei; Chen, Wei; Li, Yunhai

    2014-01-01

    Understanding the population structure and linkage disequilibrium in an association panel can effectively avoid spurious associations and improve the accuracy in association mapping. In this study, one hundred and fifty eight elite cotton (Gossypium hirsutum L.) germplasm from all over the world, which were genotyped with 212 whole genome-wide marker loci and phenotyped with an disease nursery and greenhouse screening method, were assayed for population structure, linkage disequilibrium, and association mapping of Verticillium wilt resistance. A total of 480 alleles ranging from 2 to 4 per locus were identified from all collections. Model-based analysis identified two groups (G1 and G2) and seven subgroups (G1a–c, G2a–d), and differentiation analysis showed that subgroup having a single origin or pedigree was apt to differentiate with those having a mixed origin. Only 8.12% linked marker pairs showed significant LD (P<0.001) in this association panel. The LD level for linked markers is significantly higher than that for unlinked markers, suggesting that physical linkage strongly influences LD in this panel, and LD level was elevated when the panel was classified into groups and subgroups. The LD decay analysis for several chromosomes showed that different chromosomes showed a notable change in LD decay distances for the same gene pool. Based on the disease nursery and greenhouse environment, 42 marker loci associated with Verticillium wilt resistance were identified through association mapping, which widely were distributed among 15 chromosomes. Among which 10 marker loci were found to be consistent with previously identified QTLs and 32 were new unreported marker loci, and QTL clusters for Verticillium wilt resistanc on Chr.16 were also proved in our study, which was consistent with the strong linkage in this chromosome. Our results would contribute to association mapping and supply the marker candidates for marker-assisted selection of Verticillium wilt

  5. Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

    PubMed

    Cheung, Chloe Y Y; Tang, Clara S; Xu, Aimin; Lee, Chi-Ho; Au, Ka-Wing; Xu, Lin; Fong, Carol H Y; Kwok, Kelvin H M; Chow, Wing-Sun; Woo, Yu-Cho; Yuen, Michele M A; Hai, JoJo S H; Jin, Ya-Li; Cheung, Bernard M Y; Tan, Kathryn C B; Cherny, Stacey S; Zhu, Feng; Zhu, Tong; Thomas, G Neil; Cheng, Kar-Keung; Jiang, Chao-Qiang; Lam, Tai-Hing; Tse, Hung-Fat; Sham, Pak-Chung; Lam, Karen S L

    2017-01-01

    Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery  < 6.45 × 10 -7 ). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta ] = 3.74 × 10 -15 ) in the combined analysis. We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

  6. Agriculture, population growth, and statistical analysis of the radiocarbon record.

    PubMed

    Zahid, H Jabran; Robinson, Erick; Kelly, Robert L

    2016-01-26

    The human population has grown significantly since the onset of the Holocene about 12,000 y ago. Despite decades of research, the factors determining prehistoric population growth remain uncertain. Here, we examine measurements of the rate of growth of the prehistoric human population based on statistical analysis of the radiocarbon record. We find that, during most of the Holocene, human populations worldwide grew at a long-term annual rate of 0.04%. Statistical analysis of the radiocarbon record shows that transitioning farming societies experienced the same rate of growth as contemporaneous foraging societies. The same rate of growth measured for populations dwelling in a range of environments and practicing a variety of subsistence strategies suggests that the global climate and/or endogenous biological factors, not adaptability to local environment or subsistence practices, regulated the long-term growth of the human population during most of the Holocene. Our results demonstrate that statistical analyses of large ensembles of radiocarbon dates are robust and valuable for quantitatively investigating the demography of prehistoric human populations worldwide.

  7. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations

    PubMed Central

    Li, Yang; Wang, Wen-Jing; Cao, Huiqing; Lu, Jiehua; Wu, Chong; Hu, Fang-Yuan; Guo, Jian; Zhao, Ling; Yang, Fan; Zhang, Yi-Xin; Li, Wei; Zheng, Gu-Yan; Cui, Hanbin; Chen, Xiaomin; Zhu, Zhiming; He, Hongbo; Dong, Birong; Mo, Xianming; Zeng, Yi; Tian, Xiao-Li

    2009-01-01

    FOXO1A and FOXO3A are two members of the FoxO family. FOXO3A has recently been linked to human longevity in Japanese, German and Italian populations. Here we tested the genetic contribution of FOXO1A and FOXO3A to the longevity phenotype in Han Chinese population. Six tagging SNPs from FOXO1A and FOXO3A were selected and genotyped in 1817 centenarians and younger individuals. Two SNPs of FOXO1A were found to be associated with longevity in women (P = 0.01–0.005), whereas all three SNPs of FOXO3A were associated with longevity in both genders (P = 0.005–0.001). One SNP from FOXO1A was found not to be associated with longevity. In haplotype association tests, the OR (95% CI) for haplotypes TTG and CCG of FOXO1A in association with female longevity were 0.72 (0.58–0.90) and 1.38 (1.08–1.76), P = 0.0033 and 0.0063, respectively. The haplotypes of FOXO3A were associated with longevity in men [GTC: OR (95% CI) = 0.67 (0.51–0.86), P = 0.0014; CGT: OR (95% CI) = 1.48 (1.12–1.94), P = 0.0035] and in women [GTC: OR (95% CI) = 0.75 (0.60–0.94), P = 0.0094; CGT: OR (95% CI) = 1.47 (1.16–1.86), P = 0.0009]. The haplotype association tests were validated by permutation analysis. The association of FOXO1A with female longevity was replicated in 700 centenarians and younger individuals that were sampled geographically different from the original population. Thus, we demonstrate that, unlike FOXO3A, FOXO1A is more closely associated with human female longevity, suggesting that the genetic contribution to longevity trait may be affected by genders. PMID:19793722

  8. Prostate-Specific Antigen (PSA)–Based Population Screening for Prostate Cancer: An Economic Analysis

    PubMed Central

    Tawfik, A

    2015-01-01

    Background The prostate-specific antigen (PSA) blood test has become widely used in Canada to test for prostate cancer (PC), the most common cancer among Canadian men. Data suggest that population-based PSA screening may not improve overall survival. Objectives This analysis aimed to review existing economic evaluations of population-based PSA screening, determine current spending on opportunistic PSA screening in Ontario, and estimate the cost of introducing a population-based PSA screening program in the province. Methods A systematic literature search was performed to identify economic evaluations of population-based PSA screening strategies published from 1998 to 2013. Studies were assessed for their methodological quality and applicability to the Ontario setting. An original cost analysis was also performed, using data from Ontario administrative sources and from the published literature. One-year costs were estimated for 4 strategies: no screening, current (opportunistic) screening of men aged 40 years and older, current (opportunistic) screening of men aged 50 to 74 years, and population-based screening of men aged 50 to 74 years. The analysis was conducted from the payer perspective. Results The literature review demonstrated that, overall, population-based PSA screening is costly and cost-ineffective but may be cost-effective in specific populations. Only 1 Canadian study, published 15 years ago, was identified. Approximately $119.2 million is being spent annually on PSA screening of men aged 40 years and older in Ontario, including close to $22 million to screen men younger than 50 and older than 74 years of age (i.e., outside the target age range for a population-based program). A population-based screening program in Ontario would cost approximately $149.4 million in the first year. Limitations Estimates were based on the synthesis of data from a variety of sources, requiring several assumptions and causing uncertainty in the results. For example, where

  9. Generalizability of Associations from Prostate Cancer GWAS in Multiple Populations

    PubMed Central

    Waters, Kevin M.; Le Marchand, Loic; Kolonel, Laurence N.; Monroe, Kristine R.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.

    2010-01-01

    Genome-wide association studies have identified multiple common alleles associated with prostate cancer risk in populations of European ancestry. Testing these variants in other populations is needed to assess the generalizability of the associations, and may guide fine-mapping efforts. We examined 13 of these risk variants in a multiethnic sample of 2,768 incident prostate cancer cases and 2,359 controls from the Multiethnic Cohort (MEC; African Americans, European Americans, Latinos, Japanese Americans and Native Hawaiians). We estimated ethnic-specific and pooled odds ratios and tested for ethnic heterogeneity of effects using logistic regression. In ethnic-pooled analyses, 12 of the 13 variants were positively associated with risk, with statistically significant associations (p<0.05) noted with 6 variants (odds ratio, 95% confidence interval): JAZF1, rs10486567, 1.23(1.12–1.35); Xp11.2, rs5945572, 1.31(1.13–1.51); HNF1B, rs4430796, 1.15(1.06–1.25); MSMB, rs10993994, 1.13(1.04–1.23); 11q13.2, rs7931342, 1.13(1.03–1.23); 3p12.1, rs2660753, 1.11(1.01–1.21); SLC22A3, rs9364554, 1.10(1.00–1.21); CTBP2, rs12769019, 1.11(0.99–1.25); HNF1B, rs11649743, 1.10(0.99–1.22); EHBP1, rs721048, 1.08(0.94–1.25); KLK2/3, rs2735839, 1.06(0.97–1.16); 17q24.3, rs1859962, 1.04(0.96–1.13); and LMTK2, rs6465657, 0.99(0.89–1.09). Significant ethnic heterogeneity of effects was noted for 4 variants (EHBP1, phet = 3.9×10−3; 11q13, phet = 0.023; HNF1B (rs4430796), phet = 0.026; and KLK2/3, phet = 2.0×10−3). Although power was limited in some ethnic/racial groups due to variation in sample size and allele frequencies, these findings suggest that a large fraction of prostate cancer variants identified in populations of European ancestry are global markers of risk. For many of these regions, fine-mapping in non-European samples may help localize causal alleles and better determine their contribution to prostate cancer risk in the population. PMID:19318432

  10. Associations between toenail arsenic concentration and dietary factors in a New Hampshire population.

    PubMed

    Gruber, Joann F; Karagas, Margaret R; Gilbert-Diamond, Diane; Bagley, Pamela J; Zens, M Scot; Sayarath, Vicki; Punshon, Tracy; Morris, J Steven; Cottingham, Kathryn L

    2012-06-29

    Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.

  11. Associations between toenail arsenic concentration and dietary factors in a New Hampshire population

    PubMed Central

    2012-01-01

    Background Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. Methods As part of a population-based case–control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. Results As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. Conclusion In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue. PMID:22747713

  12. Association of HFE gene mutations with nonalcoholic fatty liver disease in the Iranian population.

    PubMed

    Saremi, L; Lotfipanah, S; Mohammadi, M; Hosseinzadeh, H; Sayad, A; Saltanatpour, Z

    2016-10-31

    To determine whether the HFE gene variants H63D and C282Y are associated with NAFLD in persons with type 2 diabetes, we conducted a case-control study including 145 case of NAFLD patients with a history of type 2 diabetes and 145 matching control. The genomic DNA was extracted from the peripheral venous blood and the genotyping of HFE gene mutations was analyzed using the PCR-RFLP technique. Statistical analysis was performed using SPSS 12.0 software by χ2 test, t test and ANOVA (P<0.05). Data showed no increased frequency of HFE mutations in persons with type 2 diabetes and no association between H63D mutation and NAFLD in the study population. Also, we analyzed index of physiological variables including FBS, lipid profile (TC, TG, LDL-C, and HDL-C), BMI, HbA1c, and micro albuminuria and Cr levels). Data showed there are no relationship between these indexes and HFE gene mutations and either NAFLD as a complication of diabetes. But our results showed a relationship between C282Y mutation and NAFLD in persons with type 2 diabetes. C282Y mutation might be a genetic marker of NAFLD in Iranian population.

  13. Genetic Evaluation of Natural Populations of the Endangered Conifer Thuja koraiensis Using Microsatellite Markers by Restriction-Associated DNA Sequencing

    PubMed Central

    Hou, Lu; Cui, Yanhong; Li, Xiang; Chen, Wu; Zhang, Zhiyong; Pang, Xiaoming; Li, Yingyue

    2018-01-01

    Thuja koraiensis Nakai is an endangered conifer of high economic and ecological value in Jilin Province, China. However, studies on its population structure and conservation genetics have been limited by the lack of genomic data. Here, 37,761 microsatellites (simple sequence repeat, SSR) were detected based on 875,792 de novo-assembled contigs using a restriction-associated DNA (RAD) approach. Among these SSRs, 300 were randomly selected to test for polymorphisms and 96 obtained loci were able to amplify a fragment of expected size. Twelve polymorphic SSR markers were developed to analyze the genetic diversity and population structure of three natural populations. High genetic diversity (mean NA = 5.481, HE = 0.548) and moderate population differentiation (pairwise Fst = 0.048–0.078, Nm = 2.940–4.958) were found in this species. Molecular variance analysis suggested that most of the variation (83%) existed within populations. Combining the results of STRUCTURE, principal coordinate, and neighbor-joining analysis, the 232 individuals were divided into three genetic clusters that generally correlated with their geographical distributions. Finally, appropriate conservation strategies were proposed to protect this species. This study provides genetic information for the natural resource conservation and utilization of T. koraiensis and will facilitate further studies of the evolution and phylogeography of the species. PMID:29673217

  14. Association Between Cd Exposure and Risk of Prostate Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis.

    PubMed

    Ju-Kun, Song; Yuan, Dong-Bo; Rao, Hao-Fu; Chen, Tian-Fei; Luan, Bo-Shi; Xu, Xiao-Ming; Jiang, Fu-Neng; Zhong, Wei-De; Zhu, Jian-Guo

    2016-02-01

    Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer.Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model.In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91-1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10-2.50) in populations exposed to occupational Cd. In addition, high D-Cd intake (OR 1.07; 95% CI 0.96-1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48-1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73-1.57) for each 0.5 μg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99-1.06) for each 10 μg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer.This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer.

  15. Culture-Independent Identification of Periodontitis-Associated Porphyromonas and Tannerella Populations by Targeted Molecular Analysis

    PubMed Central

    de Lillo, A.; Booth, V.; Kyriacou, L.; Weightman, A. J.; Wade, W. G.

    2004-01-01

    Periodontitis is the commonest bacterial disease of humans and is the major cause of adult tooth loss. About half of the oral microflora is unculturable; and 16S rRNA PCR, cloning, and sequencing techniques have demonstrated the high level of species richness of the oral microflora. In the present study, a PCR primer set specific for the genera Porphyromonas and Tannerella was designed and used to analyze the bacterial populations in subgingival plaque samples from inflamed shallow and deep sites in subjects with periodontitis and shallow sites in age- and sex-matched controls. A total of 308 clones were sequenced and found to belong to one of six Porphyromonas or Tannerella species or phylotypes, one of which, Porphyromonas P3, was novel. Tannerella forsythensis was found in significantly higher proportions in patients than in controls. Porphyromonas catoniae and Tannerella phylotype BU063 appeared to be associated with shallow sites. Targeted culture-independent molecular ecology studies have a valuable role to play in the identification of bacterial targets for further investigations of the pathogenesis of bacterial infections. PMID:15583276

  16. Highly Diverse Endophytic and Soil Fusarium oxysporum Populations Associated with Field-Grown Tomato Plants

    PubMed Central

    Demers, Jill E.; Gugino, Beth K.

    2014-01-01

    The diversity and genetic differentiation of populations of Fusarium oxysporum associated with tomato fields, both endophytes obtained from tomato plants and isolates obtained from soil surrounding the sampled plants, were investigated. A total of 609 isolates of F. oxysporum were obtained, 295 isolates from a total of 32 asymptomatic tomato plants in two fields and 314 isolates from eight soil cores sampled from the area surrounding the plants. Included in this total were 112 isolates from the stems of all 32 plants, a niche that has not been previously included in F. oxysporum population genetics studies. Isolates were characterized using the DNA sequence of the translation elongation factor 1α gene. A diverse population of 26 sequence types was found, although two sequence types represented nearly two-thirds of the isolates studied. The sequence types were placed in different phylogenetic clades within F. oxysporum, and endophytic isolates were not monophyletic. Multiple sequence types were found in all plants, with an average of 4.2 per plant. The population compositions differed between the two fields but not between soil samples within each field. A certain degree of differentiation was observed between populations associated with different tomato cultivars, suggesting that the host genotype may affect the composition of plant-associated F. oxysporum populations. No clear patterns of genetic differentiation were observed between endophyte populations and soil populations, suggesting a lack of specialization of endophytic isolates. PMID:25304514

  17. Television screen time, but not computer use and reading time, is associated with cardio-metabolic biomarkers in a multiethnic Asian population: a cross-sectional study.

    PubMed

    Nang, Ei Ei Khaing; Salim, Agus; Wu, Yi; Tai, E Shyong; Lee, Jeannette; Van Dam, Rob M

    2013-05-30

    Recent evidence shows that sedentary behaviour may be an independent risk factor for cardiovascular diseases, diabetes, cancers and all-cause mortality. However, results are not consistent and different types of sedentary behaviour might have different effects on health. Thus the aim of this study was to evaluate the association between television screen time, computer/reading time and cardio-metabolic biomarkers in a multiethnic urban Asian population. We also sought to understand the potential mediators of this association. The Singapore Prospective Study Program (2004-2007), was a cross-sectional population-based study in a multiethnic population in Singapore. We studied 3305 Singaporean adults of Chinese, Malay and Indian ethnicity who did not have pre-existing diseases and conditions that could affect their physical activity. Multiple linear regression analysis was used to assess the association of television screen time and computer/reading time with cardio-metabolic biomarkers [blood pressure, lipids, glucose, adiponectin, C reactive protein and homeostasis model assessment of insulin resistance (HOMA-IR)]. Path analysis was used to examine the role of mediators of the observed association. Longer television screen time was significantly associated with higher systolic blood pressure, total cholesterol, triglycerides, C reactive protein, HOMA-IR, and lower adiponectin after adjustment for potential socio-demographic and lifestyle confounders. Dietary factors and body mass index, but not physical activity, were potential mediators that explained most of these associations between television screen time and cardio-metabolic biomarkers. The associations of television screen time with triglycerides and HOMA-IR were only partly explained by dietary factors and body mass index. No association was observed between computer/ reading time and worse levels of cardio-metabolic biomarkers. In this urban Asian population, television screen time was associated with worse

  18. A genome-wide association study on photic sneeze syndrome in a Japanese population.

    PubMed

    Sasayama, Daimei; Asano, Shinya; Nogawa, Shun; Takahashi, Shoko; Saito, Kenji; Kunugi, Hiroshi

    2018-03-20

    Photic sneeze syndrome (PSS) is characterized by a tendency to sneeze when the eye is exposed to bright light. Recent genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) associated with PSS in Caucasian populations. We performed a GWAS on PSS in Japanese individuals who responded to a web-based survey and provided saliva samples. After quality control, genotype data of 210,086 SNPs in 11,409 individuals were analyzed. The overall prevalence of PSS was 3.2%. Consistent with previous reports, SNPs at 3p12.1 were associated with PSS at genome-wide significance (p < 5.0 × 10 -8 ). Furthermore, two novel loci at 9q34.2 and 4q35.2 reached suggestive significance (p < 5.0 × 10 -6 ). Our data also provided evidence supporting the two additional SNPs on 2q22.3 and 9q33.2 reportedly associated with PSS. Our study reproduced previous findings in Caucasian populations and further suggested novel PSS loci in the Japanese population.

  19. Population structure and genome-wide association analysis for frost tolerance in oat using continuous SNP array signal intensity ratios.

    PubMed

    Tumino, Giorgio; Voorrips, Roeland E; Rizza, Fulvia; Badeck, Franz W; Morcia, Caterina; Ghizzoni, Roberta; Germeier, Christoph U; Paulo, Maria-João; Terzi, Valeria; Smulders, Marinus J M

    2016-09-01

    Infinium SNP data analysed as continuous intensity ratios enabled associating genotypic and phenotypic data from heterogeneous oat samples, showing that association mapping for frost tolerance is a feasible option. Oat is sensitive to freezing temperatures, which restricts the cultivation of fall-sown or winter oats to regions with milder winters. Fall-sown oats have a longer growth cycle, mature earlier, and have a higher productivity than spring-sown oats, therefore improving frost tolerance is an important goal in oat breeding. Our aim was to test the effectiveness of a Genome-Wide Association Study (GWAS) for mapping QTLs related to frost tolerance, using an approach that tolerates continuously distributed signals from SNPs in bulked samples from heterogeneous accessions. A collection of 138 European oat accessions, including landraces, old and modern varieties from 27 countries was genotyped using the Infinium 6K SNP array. The SNP data were analyzed as continuous intensity ratios, rather than converting them into discrete values by genotype calling. PCA and Ward's clustering of genetic similarities revealed the presence of two main groups of accessions, which roughly corresponded to Continental Europe and Mediterranean/Atlantic Europe, although a total of eight subgroups can be distinguished. The accessions were phenotyped for frost tolerance under controlled conditions by measuring fluorescence quantum yield of photosystem II after a freezing stress. GWAS were performed by a linear mixed model approach, comparing different corrections for population structure. All models detected three robust QTLs, two of which co-mapped with QTLs identified earlier in bi-parental mapping populations. The approach used in the present work shows that SNP array data of heterogeneous hexaploid oat samples can be successfully used to determine genetic similarities and to map associations to quantitative phenotypic traits.

  20. Associations between SLC2A9 polymorphisms and gout susceptibility : A meta-analysis.

    PubMed

    Lee, Y H; Seo, Y H; Kim, J-H; Choi, S J; Ji, J D; Song, G G

    2017-02-01

    The aim of this study was to determine whether polymorphisms in solute carrier family 2 and facilitated glucose transporter member 9 (SLC2A9) are associated with susceptibility to gout. A meta-analysis was conducted on associations between the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 and gout susceptibility using fixed and random effects models. Eleven comparative studies comprising 1,472 patients and 3,269 controls from Caucasian and Asian populations were included in this meta-analysis. The meta-analysis identified a significant negative association between gout and allele 2 (minor) of the rs12510549 polymorphism in the overall population (OR = 0.641, 95 % CI = 0.540-0.761, P = 4.1 × 10 -7 ). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.647, 95 % CI = 0.542-0.771, P = 1.2 × 10 -6 ) but not in Asians (OR = 0.515, 95 % CI = 0.214-1.236, P = 0.137). The meta-analysis showed a significant negative association between gout and allele 2 of the rs16890979 polymorphism in all study subjects (OR = 0.229, 95 % CI = 0.084-0.628, P = 0.004). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.469, 95 % CI = 0.317-0.695, P = 1.6 × 10 -6 ) and in Asians (OR = 0.192, 95 % CI = 0.072-0.513, P = 0.001). A significant negative association was found between allele 2 of the rs1014290 polymorphism and gout susceptibility in Asians (OR = 0.597, 95 % CI = 0.478-0.746, P = 5.4 × 10 -6 ) but not in Caucasians (OR = 0.778, 95 % CI = 0.595-1.043, P = 0.095). This meta-analysis shows that the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 protect against the development of gout in Caucasians and/or Asians.

  1. Cluster analysis in phenotyping a Portuguese population.

    PubMed

    Loureiro, C C; Sa-Couto, P; Todo-Bom, A; Bousquet, J

    2015-09-03

    Unbiased cluster analysis using clinical parameters has identified asthma phenotypes. Adding inflammatory biomarkers to this analysis provided a better insight into the disease mechanisms. This approach has not yet been applied to asthmatic Portuguese patients. To identify phenotypes of asthma using cluster analysis in a Portuguese asthmatic population treated in secondary medical care. Consecutive patients with asthma were recruited from the outpatient clinic. Patients were optimally treated according to GINA guidelines and enrolled in the study. Procedures were performed according to a standard evaluation of asthma. Phenotypes were identified by cluster analysis using Ward's clustering method. Of the 72 patients enrolled, 57 had full data and were included for cluster analysis. Distribution was set in 5 clusters described as follows: cluster (C) 1, early onset mild allergic asthma; C2, moderate allergic asthma, with long evolution, female prevalence and mixed inflammation; C3, allergic brittle asthma in young females with early disease onset and no evidence of inflammation; C4, severe asthma in obese females with late disease onset, highly symptomatic despite low Th2 inflammation; C5, severe asthma with chronic airflow obstruction, late disease onset and eosinophilic inflammation. In our study population, the identified clusters were mainly coincident with other larger-scale cluster analysis. Variables such as age at disease onset, obesity, lung function, FeNO (Th2 biomarker) and disease severity were important for cluster distinction. Copyright © 2015. Published by Elsevier España, S.L.U.

  2. Assessment of Geographic and Host-Associated Population Variations of the Carob Moth, Ectomyelois ceratoniae, on Pomegranate, Fig, Pistachio and Walnut, Using AFLP Markers

    PubMed Central

    Mozaffarian, Fariba; Mardi, Mohsen; Sarafrazi, Alimorad; Nouri Ganbalani, Gadir

    2008-01-01

    The carob moth, Ectomyelois ceratoniae (Zeller 1839) (Lepidoptera: Pyralidae) is the most important pest of pomegranate, Punica granatum L. (Myrtales: Ponicaceae), in Iran. In this study, 6 amplified fragment length polymorphism primer combinations were used to survey the genetic structure of the geographic and putative host-associated populations of this pest in Iran. An AMOVA was performed on test populations. Pairwise differences, Mantel test, multidimensional analysis, cluster analysis and migration rate were calculated for 5 geographic populations of E. ceratoniae sharing the same host, pomegranate. In another part of the study, 3 comparisons were performed on pairwise populations that were collected on different hosts (pomegranate, fig, pistachio and walnut) in same geographic regions. The results showed high within population variation (85.51% of total variation), however geographic populations differed significantly. The Mantel test did not show correlations between genetic and geographic distances. The probable factors that affect genetic distances are discussed. Multidimensional scaling analysis, migration rate and cluster analysis on geographic populations showed that the Arsanjan population was the most different from the others while the Saveh population was more similar to the Sabzevar population. The comparisons didn't show any host fidelity in test populations. It seems that the ability of E. ceratoniae to broaden its host range with no fidelity to hosts can decrease the efficiency of common control methods that are used on pomegranate. The results of this study suggest that in spite of the effects of geographic barriers, high within-population genetic variation, migration rate and gene flow can provide the opportunity for emerging new phenotypes or behaviors in pest populations, such as broadening host range, changing egg lying places, or changing over-wintering sites to adapt to difficult conditions such as those caused by intensive control

  3. Population viability analysis for endangered Roanoke logperch

    USGS Publications Warehouse

    Roberts, James H.; Angermeier, Paul; Anderson, Gregory B.

    2016-01-01

    A common strategy for recovering endangered species is ensuring that populations exceed the minimum viable population size (MVP), a demographic benchmark that theoretically ensures low long-term extinction risk. One method of establishing MVP is population viability analysis, a modeling technique that simulates population trajectories and forecasts extinction risk based on a series of biological, environmental, and management assumptions. Such models also help identify key uncertainties that have a large influence on extinction risk. We used stochastic count-based simulation models to explore extinction risk, MVP, and the possible benefits of alternative management strategies in populations of Roanoke logperch Percina rex, an endangered stream fish. Estimates of extinction risk were sensitive to the assumed population growth rate and model type, carrying capacity, and catastrophe regime (frequency and severity of anthropogenic fish kills), whereas demographic augmentation did little to reduce extinction risk. Under density-dependent growth, the estimated MVP for Roanoke logperch ranged from 200 to 4200 individuals, depending on the assumed severity of catastrophes. Thus, depending on the MVP threshold, anywhere from two to all five of the logperch populations we assessed were projected to be viable. Despite this uncertainty, these results help identify populations with the greatest relative extinction risk, as well as management strategies that might reduce this risk the most, such as increasing carrying capacity and reducing fish kills. Better estimates of population growth parameters and catastrophe regimes would facilitate the refinement of MVP and extinction-risk estimates, and they should be a high priority for future research on Roanoke logperch and other imperiled stream-fish species.

  4. The association between emotions and eating behaviour in an obese population with binge eating disorder.

    PubMed

    Nicholls, W; Devonport, T J; Blake, M

    2016-01-01

    There is utility in understanding the antecedents of binge eating (BE), with a view to explaining poorer weight loss treatment responses in this subgroup. A systematic review was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the aim of exploring associations between emotions and eating behaviour in a population affected by obesity and binge eating disorder (BED). A comprehensive literature search of four electronic databases (2004-2014) yielded 15 studies for inclusion. Included studies performed poorly on data quality analysis with respect to controlling for confounding variables, and sample size. Included papers largely focused on negative emotions as antecedents of BE; depression was consistently associated with a BED-obese classification and BE. Negative mood, sadness, tension and instability of emotions were found to be antecedents of BE in an adult BED-obese sample. However, findings were mixed regarding the role of stress, anger and positive emotions within the BED-obese population. Recommendations are presented for the identification of BED, and ecologically valid experimental designs that further understanding of the complex and varied emotions that associate with BE. The implications of these and other limitations for both researchers and practitioners are discussed. The paper concludes with recommendations for future research alongside suggestions for practitioners. © 2015 World Obesity. © 2015 World Obesity.

  5. Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

    PubMed Central

    Simonic, I; Gericke, G S; Ott, J; Weber, J L

    1998-01-01

    Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q. PMID:9718333

  6. Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

    PubMed

    Simonic, I; Gericke, G S; Ott, J; Weber, J L

    1998-09-01

    Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q.

  7. Genome-wide association study of ancestry-specific TB risk in the South African Coloured population

    PubMed Central

    Chimusa, Emile R.; Zaitlen, Noah; Daya, Michelle; Möller, Marlo; van Helden, Paul D.; Mulder, Nicola J.; Price, Alkes L.; Hoal, Eileen G.

    2014-01-01

    The worldwide burden of tuberculosis (TB) remains an enormous problem, and is particularly severe in the admixed South African Coloured (SAC) population residing in the Western Cape. Despite evidence from twin studies suggesting a strong genetic component to TB resistance, only a few loci have been identified to date. In this work, we conduct a genome-wide association study (GWAS), meta-analysis and trans-ethnic fine mapping to attempt the replication of previously identified TB susceptibility loci. Our GWAS results confirm the WT1 chr11 susceptibility locus (rs2057178: odds ratio = 0.62, P = 2.71e−06) previously identified by Thye et al., but fail to replicate previously identified polymorphisms in the TLR8 gene and locus 18q11.2. Our study demonstrates that the genetic contribution to TB risk varies between continental populations, and illustrates the value of including admixed populations in studies of TB risk and other complex phenotypes. Our evaluation of local ancestry based on the real and simulated data demonstrates that case-only admixture mapping is currently impractical in multi-way admixed populations, such as the SAC, due to spurious deviations in average local ancestry generated by current local ancestry inference methods. This study provides insights into identifying disease genes and ancestry-specific disease risk in multi-way admixed populations. PMID:24057671

  8. Microbial Populations Associated with Treatment of an Industrial Dye Effluent in an Anaerobic Baffled Reactor

    PubMed Central

    Plumb, Jason J.; Bell, Joanne; Stuckey, David C.

    2001-01-01

    Fluorescent in situ hybridization (FISH) using 16S and 23S rRNA-targeted probes together with construction of an archaeal 16S ribosomal DNA (rDNA) clone library was used to characterize the microbial populations of an anaerobic baffled reactor successfully treating industrial dye waste. Wastewater produced during the manufacture of food dyes containing several different azo and other dye compounds was decolorized and degraded under sulfidogenic and methanogenic conditions. Use of molecular methods to describe microbial populations showed that a diverse group of Bacteria and Archaea was involved in this treatment process. FISH enumeration showed that members of the gamma subclass of the class Proteobacteria and bacteria in the Cytophaga-Flexibacter-Bacteroides phylum, together with sulfate-reducing bacteria, were prominent members of a mixed bacterial population. A combination of FISH probing and analysis of 98 archaeal 16S rDNA clone inserts revealed that together with the bacterial population, a methanogenic population dominated by Methanosaeta species and containing species of Methanobacterium and Methanospirillum and a relatively unstudied methanogen, Methanomethylovorans hollandica, contributed to successful anaerobic treatment of the industrial waste. We suggest that sulfate reducers, or more accurately sulfidogenic bacteria, together with M. hollandica contribute considerably to the treatment process through metabolism of dye-associated sulfonate groups and subsequent conversion of sulfur compounds to carbon dioxide and methane. PMID:11425746

  9. Gender Difference on the Association between Dietary Patterns and Obesity in Chinese Middle-Aged and Elderly Populations.

    PubMed

    Yuan, Ya-Qun; Li, Fan; Meng, Pai; You, Jie; Wu, Min; Li, Shu-Guang; Chen, Bo

    2016-07-23

    Dietary patterns are linked to obesity, but the gender difference in the association between dietary patterns and obesity remains unclear. We explored this gender difference in a middle-aged and elderly populations in Shanghai. Residents (n = 2046; aged ≥45 years; 968 men and 1078 women) who participated in the Shanghai Food Consumption Survey were studied. Factor analysis of data from four periods of 24-h dietary recalls (across 2012-2014) identified dietary patterns. Height, body weight, and waist circumference were measured to calculate the body mass index. A log binominal model examined the association between dietary patterns and obesity, stratified by gender. Four dietary patterns were identified for both genders: rice staple, wheat staple, snacks, and prudent patterns. The rice staple pattern was associated positively with abdominal obesity in men (prevalence ratio (PR) = 1.358; 95% confidence interval (CI) 1.132-1.639; p = 0.001), but was associated negatively with general obesity in women (PR = 0.745; 95% CI: 0.673-0.807; p = 0.031). Men in the highest quartile of the wheat staple pattern had significantly greater risk of central obesity (PR = 1.331; 95% CI: 1.094-1.627; p = 0.005). There may be gender differences in the association between dietary patterns and obesity in middle-aged and elderly populations in Shanghai, China.

  10. Gender Difference on the Association between Dietary Patterns and Obesity in Chinese Middle-Aged and Elderly Populations

    PubMed Central

    Yuan, Ya-Qun; Li, Fan; Meng, Pai; You, Jie; Wu, Min; Li, Shu-Guang; Chen, Bo

    2016-01-01

    Dietary patterns are linked to obesity, but the gender difference in the association between dietary patterns and obesity remains unclear. We explored this gender difference in a middle-aged and elderly populations in Shanghai. Residents (n = 2046; aged ≥45 years; 968 men and 1078 women) who participated in the Shanghai Food Consumption Survey were studied. Factor analysis of data from four periods of 24-h dietary recalls (across 2012–2014) identified dietary patterns. Height, body weight, and waist circumference were measured to calculate the body mass index. A log binominal model examined the association between dietary patterns and obesity, stratified by gender. Four dietary patterns were identified for both genders: rice staple, wheat staple, snacks, and prudent patterns. The rice staple pattern was associated positively with abdominal obesity in men (prevalence ratio (PR) = 1.358; 95% confidence interval (CI) 1.132–1.639; p = 0.001), but was associated negatively with general obesity in women (PR = 0.745; 95% CI: 0.673–0.807; p = 0.031). Men in the highest quartile of the wheat staple pattern had significantly greater risk of central obesity (PR = 1.331; 95% CI: 1.094–1.627; p = 0.005). There may be gender differences in the association between dietary patterns and obesity in middle-aged and elderly populations in Shanghai, China. PMID:27455322

  11. Analysis of Intervention Strategies for Inhalation Exposure to Polycyclic Aromatic Hydrocarbons and Associated Lung Cancer Risk Based on a Monte Carlo Population Exposure Assessment Model

    PubMed Central

    Zhou, Bin; Zhao, Bin

    2014-01-01

    It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs), a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF) and potential impact fraction (PIF) of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making. PMID:24416436

  12. Analysis of intervention strategies for inhalation exposure to polycyclic aromatic hydrocarbons and associated lung cancer risk based on a Monte Carlo population exposure assessment model.

    PubMed

    Zhou, Bin; Zhao, Bin

    2014-01-01

    It is difficult to evaluate and compare interventions for reducing exposure to air pollutants, including polycyclic aromatic hydrocarbons (PAHs), a widely found air pollutant in both indoor and outdoor air. This study presents the first application of the Monte Carlo population exposure assessment model to quantify the effects of different intervention strategies on inhalation exposure to PAHs and the associated lung cancer risk. The method was applied to the population in Beijing, China, in the year 2006. Several intervention strategies were designed and studied, including atmospheric cleaning, smoking prohibition indoors, use of clean fuel for cooking, enhancing ventilation while cooking and use of indoor cleaners. Their performances were quantified by population attributable fraction (PAF) and potential impact fraction (PIF) of lung cancer risk, and the changes in indoor PAH concentrations and annual inhalation doses were also calculated and compared. The results showed that atmospheric cleaning and use of indoor cleaners were the two most effective interventions. The sensitivity analysis showed that several input parameters had major influence on the modeled PAH inhalation exposure and the rankings of different interventions. The ranking was reasonably robust for the remaining majority of parameters. The method itself can be extended to other pollutants and in different places. It enables the quantitative comparison of different intervention strategies and would benefit intervention design and relevant policy making.

  13. Omalizumab therapy is associated with reduced circulating basophil populations in asthmatic children

    PubMed Central

    Hill, D.A.; Siracusa, M.; Ruymann, K.; Wojno, E.D. Tait; Artis, D.; Spergel, J.M.

    2014-01-01

    Basophils have been implicated in promoting the early development of TH2 cell responses in some murine models of TH2 cytokine-associated inflammation. However, the specific role of basophils in allergic asthma remains an active area of research. Recent studies in animal models and human subjects suggest that IgE may regulate the homeostasis of human basophil populations. Here, we examine basophil populations in children with severe asthma before and during therapy with the IgE directed monoclonal antibody omalizumab. Omalizumab therapy was associated with a significant reduction in circulating basophil numbers, a finding that was concurrent with improved clinical outcomes. The observation that circulating basophils are reduced following omalizumab therapy supports a mechanistic link between IgE levels and circulating basophil populations and may provide new insights into one mechanism by which omalizumab improves asthma symptoms. PMID:24611974

  14. In search of causal variants: refining disease association signals using cross-population contrasts.

    PubMed

    Saccone, Nancy L; Saccone, Scott F; Goate, Alison M; Grucza, Richard A; Hinrichs, Anthony L; Rice, John P; Bierut, Laura J

    2008-08-29

    Genome-wide association (GWA) using large numbers of single nucleotide polymorphisms (SNPs) is now a powerful, state-of-the-art approach to mapping human disease genes. When a GWA study detects association between a SNP and the disease, this signal usually represents association with a set of several highly correlated SNPs in strong linkage disequilibrium. The challenge we address is to distinguish among these correlated loci to highlight potential functional variants and prioritize them for follow-up. We implemented a systematic method for testing association across diverse population samples having differing histories and LD patterns, using a logistic regression framework. The hypothesis is that important underlying biological mechanisms are shared across human populations, and we can filter correlated variants by testing for heterogeneity of genetic effects in different population samples. This approach formalizes the descriptive comparison of p-values that has typified similar cross-population fine-mapping studies to date. We applied this method to correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-American samples. Of the 10 SNPs genotyped in the r2 > or = 0.8 bin for rs16969968, three demonstrated significant cross-population heterogeneity and are filtered from priority follow-up; the remaining SNPs include rs16969968 (heterogeneity p = 0.75). Though the power to filter out rs16969968 is reduced due to the difference in allele frequency in the two groups, the results nevertheless focus attention on a smaller group of SNPs that includes the non-synonymous SNP rs16969968, which retains a similar effect size (odds ratio) across both population samples. Filtering out SNPs that demonstrate cross-population heterogeneity enriches for variants more likely to be important and causative. Our approach provides an important and effective

  15. Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population.

    PubMed

    Hallberg, Pär; Eriksson, Niclas; Ibañez, Luisa; Bondon-Guitton, Emmanuelle; Kreutz, Reinhold; Carvajal, Alfonso; Lucena, M Isabel; Ponce, Esther Sancho; Molokhia, Mariam; Martin, Javier; Axelsson, Tomas; Yue, Qun-Ying; Magnusson, Patrik K E; Wadelius, Mia

    2016-06-01

    Drug-induced agranulocytosis is a potentially life-threatening adverse reaction. Genome-wide association studies (GWASs) in ethnic Chinese people in Taiwan and Hong Kong have shown an association between agranulocytosis induced by antithyroid drugs and the HLA alleles HLA-B*38:02 and HLA-DRB1*08:03. We aimed to identify genetic variants associated with antithyroid drug-induced agranulocytosis in a white European population. We did a GWAS in 234 European adults with any non-chemotherapy drug-induced agranulocytosis (absolute neutrophil count ≤0·5 × 10(9)/L [≤500/μL]) and 5170 population controls. 39 of the 234 patients had agranulocytosis that was induced by antithyroid drugs (thiamazole [methimazole], carbimazole, or propylthiouracil). After imputation and HLA allele prediction, 9 380 034 single nucleotide polymorphisms (SNPs) and 180 HLA alleles were tested for association. The genome-wide significance threshold was p<5 × 10(-8). Agranulocytosis induced by non-chemotherapy drugs in general was significantly associated with the HLA region on chromosome 6, with odds ratios (ORs) of 3·24 (95% CI 2·31-4·55, p=1·20 × 10(-11)) for HLA-B*27:05 and 3·57 (2·61-4·90, p=2·32 × 10(-15)) for the top SNP (rs114291795). Drug-specific analysis showed that the association with HLA-B*27:05 was largely driven by cases induced by antithyroid drugs. In a multiple logistic regression model, the OR for HLA-B*27:05 was 7·30 (3·81-13·96) when antithyroid drug-induced agranulocytosis was compared with population controls (p=1·91 × 10(-9)) and 16·91 (3·44-83·17) when compared with a small group of hyperthyroid controls (p=5·04 × 10(-4)). Three SNPs were strongly associated with antithyroid drug-induced agranulocytosis: rs652888 (OR 4·73, 95% CI 3·00-7·44, p=1·92 × 10(-11)) and rs199564443 (17·42, 7·38-41·12, p=7·04 × 10(-11)), which were independent of HLA-B*27:05, and rs1071816 (5·27, 3·06-9·10, p=2·35 × 10

  16. CNV analysis in the Lithuanian population.

    PubMed

    Urnikyte, A; Domarkiene, I; Stoma, S; Ambrozaityte, L; Uktveryte, I; Meskiene, R; Kasiulevičius, V; Burokiene, N; Kučinskas, V

    2016-05-04

    Although copy number variation (CNV) has received much attention, knowledge about the characteristics of CNVs such as occurrence rate and distribution in the genome between populations and within the same population is still insufficient. In this study, Illumina 770 K HumanOmniExpress-12 v1.0 (and v1.1) arrays were used to examine the diversity and distribution of CNVs in 286 unrelated individuals from the two main ethnolinguistic groups of the Lithuanian population (Aukštaičiai and Žemaičiai) (see Additional file 3). For primary data analysis, the Illumina GenomeStudio™ Genotyping Module v1.9 and two algorithms, cnvPartition 3.2.0 and QuantiSNP 2.0, were used to identify high-confidence CNVs. A total of 478 autosomal CNVs were detected by both algorithms, and those were clustered in 87 copy number variation regions (CNVRs), spanning ~12.5 Mb of the genome (see Table 1). At least 8.6 % of the CNVRs were unique and had not been reported in the Database of Genomic Variants. Most CNVRs (57.5 %) were rare, with a frequency of <1 %, whereas common CNVRs with at least 5 % frequency made up only 1.1 % of all CNVRs identified. About 49 % of non-singleton CNVRs were shared between Aukštaičiai and Žemaičiai, and the remaining CNVRs were specific to each group. Many of the CNVs detected (66 %) overlapped with known UCSC gene regions. The ethnolinguistic groups of the Lithuanian population could not be differentiated based on CNV profiles, which may reflect their geographical proximity and suggest the homogeneity of the Lithuanian population. In addition, putative novel CNVs unique to the Lithuanian population were identified. The results of our study enhance the CNV map of the Lithuanian population.

  17. Assessment of association between lipoxygenase genes variants in elderly Greek population and type 2 diabetes mellitus.

    PubMed

    Tsekmekidou, Xanthippi A; Kotsa, Kalliopi D; Tsetsos, Fotis S; Didangelos, Triantafyllos P; Georgitsi, Marianthi A; Roumeliotis, Athanasios K; Panagoutsos, Stylianos A; Thodis, Elias D; Theodoridis, Marios T; Papanas, Nikolaos P; Papazoglou, Dimitrios A; Pasadakis, Ploumis S; Eustratios, Maltezos S; Paschou, Peristera I; Yovos, John G

    2018-02-01

    Inflammation plays a pivotal role in the pathogenesis of diabetes and its complications. Arachidonic acid lipoxygenases have been intensively studied in their role in inflammation in metabolic pathways. Thus, we aimed to explore variants of lipoxygenase genes (arachidonate lipoxygenase genes) in a diabetes adult population using a case-control study design. Study population consisted of 1285 elderly participants, 716 of whom had type 2 diabetes mellitus. The control group consisted of non-diabetes individuals with no history of diabetes history and with a glycated haemoglobin <6.5% (<48 mmol/mol)] and fasting plasma glucose levels <126 mg/dL. Blood samples were genotyped on Illumina Infinium PsychArray. Variants of ALOX5, ALOX5AP, ALOX12, ALOX15 were selected. All statistical analyses were undertaken within PLINK and SPSS packages utilising permutation analysis tests. Our findings showed an association of rs9669952 (odds ratio = 0.738, p = 0.013) and rs1132340 (odds ratio = 0.652, p = 0.008) in ALOX5AP and rs11239524 in ALOX5 gene with disease (odds ratio = 0.808, p = 0.038). Rs9315029 which is located near arachidonate ALOX5AP also associated with type 2 diabetes mellitus ( p = 0.025). No variant of ALOX12 and ALOX15 genes associated with disease. These results indicate a potential protective role of ALOX5AP and 5-arachidonate lipoxygenase gene in diabetes pathogenesis, indicating further the importance of the relationship between diabetes and inflammation. Larger population studies are required to replicate our findings.

  18. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia.

    PubMed

    Shunmugam, Vicneswari; Say, Yee-How

    2016-02-01

    α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population. Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype.

  19. Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Liu, Mengying; Bian, Chen; Zhang, Jiqiang; Wen, Feng

    2014-03-01

    The relationship between Apolipoprotein E (ApoE) genotype and the risk of Alzheimer's disease (AD) is relatively well established in Caucasians, but less established in other ethnicities. To examine the association between ApoE polymorphism and the onset of AD in Chinese population, we searched the commonly used electronic databases between January 2000 and November 2013 for relevant studies. Total 20 studies, including 1576 cases and 1741 controls, were retrieved. The results showed statistically significant positive association between risk factor ɛ4 allele carriers and AD in Chinese population (OR = 3.93, 95% CI = 3.37-4.58, P < 0.00001). Genotype ApoE ɛ4/ɛ4 and ɛ4/ɛ3 have statistically significant association with AD as well (ɛ4/ɛ4: OR = 11.76, 95% CI = 6.38-21.47, P < 0.00001; ɛ4/ɛ3: OR = 3.08, 95% CI = 2.57-3.69, P < 0.00001). Furthermore, the frequency of the ApoE ɛ3 is lower in AD than that in the health controls, and the difference of ɛ3 allele is also statistically significant (OR = 0.42, 95% CI = 0.37-0.47, P < 0.00001). No significant heterogeneity was observed among all studies. This meta-analysis suggests that the subject with at least one ApoE ɛ4 allele has higher risk suffering from AD than controls in Chinese population. The results also provide a support for the protection effect of ApoE ɛ3 allele in developing AD.

  20. Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

    PubMed

    Sul, Jae Hoon; Bilow, Michael; Yang, Wen-Yun; Kostem, Emrah; Furlotte, Nick; He, Dan; Eskin, Eleazar

    2016-03-01

    Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants.

  1. Cross-Population Joint Analysis of eQTLs: Fine Mapping and Functional Annotation

    PubMed Central

    Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2015-01-01

    Mapping expression quantitative trait loci (eQTLs) has been shown as a powerful tool to uncover the genetic underpinnings of many complex traits at molecular level. In this paper, we present an integrative analysis approach that leverages eQTL data collected from multiple population groups. In particular, our approach effectively identifies multiple independent cis-eQTL signals that are consistent across populations, accounting for population heterogeneity in allele frequencies and linkage disequilibrium patterns. Furthermore, by integrating genomic annotations, our analysis framework enables high-resolution functional analysis of eQTLs. We applied our statistical approach to analyze the GEUVADIS data consisting of samples from five population groups. From this analysis, we concluded that i) jointly analysis across population groups greatly improves the power of eQTL discovery and the resolution of fine mapping of causal eQTL ii) many genes harbor multiple independent eQTLs in their cis regions iii) genetic variants that disrupt transcription factor binding are significantly enriched in eQTLs (p-value = 4.93 × 10-22). PMID:25906321

  2. IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population.

    PubMed

    Shen, Chen; Jiao, Wei-Wei; Feng, Wei-Xing; Wu, Xi-Rong; Xiao, Jing; Miao, Qing; Sun, Lin; Wang, Bin-Bin; Wang, Jing; Liu, Fang; Shen, Dan; Shen, A-Dong

    2013-09-01

    Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary

  3. Association of volunteering with mental well-being: a lifecourse analysis of a national population-based longitudinal study in the UK

    PubMed Central

    Tabassum, Faiza; Mohan, John; Smith, Peter

    2016-01-01

    Objectives The association of volunteering with well-being has been found in previous research, but mostly among older people. The aim of this study was to examine the association of volunteering with mental well-being among the British population across the life course. Design British Household Panel Survey, a population-based longitudinal study. Setting UK. Participants 66 343 observations (person-years). Main outcome measures Mental well-being was measured by using the General Health Questionnaire (GHQ-12 or GHQ); high values denote high mental disorder. Four groups of volunteering participation were created: frequent (once a week), infrequent (once a month/several times a year), rare (once or less a year) and never. Multilevel linear models were used to analyse variations in mental well-being over the life course by levels of volunteering. Results When not considering age, those who engaged in volunteering regularly appeared to experience higher levels of mental well-being than those who never volunteered. To explore the association of volunteering with the GHQ across the life course, interaction terms were fitted between age and volunteering. The interactions were significant, demonstrating that these associations vary by age. The association between volunteering and well-being did not emerge during early adulthood to mid-adulthood, instead becoming apparent above the age of 40 years and continuing up to old age. Moreover, in early adulthood, the absence of engagement in voluntary activity was not related to mental well-being, but GHQ scores for this group increased sharply with age, levelling off after the age of 40 and then increasing again above the age of 70 years. The study also indicates variation in GHQ scores (65%) within individuals across time, suggesting evidence of lifecourse effects. Conclusions We conclude that volunteering may be more meaningful for mental well-being at some points of time in the life course. PMID:27503861

  4. Association of computed tomography-derived left ventricular size with major cardiovascular events in the general population: the Heinz Nixdorf recall study.

    PubMed

    Dykun, Iryna; Geisel, Marie H; Kälsch, Hagen; Lehmann, Nils; Bauer, Marcus; Moebus, Susanne; Jöckel, Karl-Heinz; Möhlenkamp, Stefan; Erbel, Raimund; Mahabadi, Amir A

    2015-05-01

    To investigate the relationship between LV size as determined by non-contrast enhanced cardiac CT with incident cardiovascular disease in the general population free of clinical cardiovascular disease. LV axial area was quantified from non-contrast CT in axial, end-diastolic images at a mid-ventricular slice in participants from the population-based Heinz Nixdorf recall study, free of cardiovascular disease (n=3926, 59±8years, 53%female). LV size index (LVI) was defined as the quotient of LV area and body surface area. Major CV events (coronary events, stroke, CV death) were assessed during follow-up. Association of LVI with events was assessed using Cox regression analysis in unadjusted and multivariable adjusted models. During 8.0±1.5years of follow-up, 219 subjects developed a major CV event. Those with events had larger LVI at baseline (2258±352 vs. 2149±276 mm2/m2, p<0.0001). In univariate analysis, increase of LVI by 1 standard deviation was associated with 40% higher risk of events (HR(95%CI):1.41(1.26-1.59), p<0.0001). Associations remained statistically significant after adjustment for CV risk factors (1.24(1.10-1.40), p=0.0007) and when further adjusting for CAC (1.21(1.07-1.37), p=0.003). There was a trend towards stronger association for subjects with low CAC-score (CAC<100:1.41(1.16-1.71), p=0.0005, CAC≥100:1.24(1.06-1.44), p=0.006) in univariate analysis which persisted after multivariable adjustment (CAC<100: 1.41(1.14-1.73), p=0.001, CAC≥100: 1.12(0.96-1.31), p=0.16). CT-derived LV size is associated with incident major CV events independent of traditional risk factors and CAC-score in a population-based cohort and may improve the prediction of hard events especially in subjects with low CAC-scores. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Population resequencing reveals candidate genes associated with salinity adaptation of the Pacific oyster Crassostrea gigas.

    PubMed

    She, Zhicai; Li, Li; Meng, Jie; Jia, Zhen; Que, Huayong; Zhang, Guofan

    2018-06-06

    The Pacific oyster Crassostrea gigas is an important cultivated shellfish. As a euryhaline species, it has evolved adaptive mechanisms responding to the complex and changeable intertidal environment that it inhabits. To investigate the genetic basis of this salinity adaptation mechanism, we conducted a genome-wide association study using phenotypically differentiated populations (hyposalinity and hypersalinity adaptation populations, and control population), and confirmed our results using an independent population, high-resolution melting, and mRNA expression analysis. For the hyposalinity adaptation, we determined 24 genes, including Cg_CLCN7 (chloride channel protein 7) and Cg_AP1 (apoptosis 1 inhibitor), involved in the ion/water channel and transporter mechanisms, free amino acid and reactive oxygen species metabolism, immune responses, and chemical defence. Three SNPs located on these two genes were significantly differentiated between groups, as was Cg_CLCN7. For the hypersalinity adaptation, the biological process for positive regulating the developmental process was enriched. Enriched gene functions were focused on transcriptional regulation, signal transduction, and cell growth and differentiation, including calmodulin (Cg_CaM) and ficolin-2 (Cg_FCN2). These genes and polymorphisms possibly play an important role in oyster hyposalinity and hypersalinity adaptation. They not only further our understanding of salinity adaptation mechanisms but also provide markers for highly adaptable oyster strains suitable for breeding.

  6. Genetic Diversity and Association Studies in US Hispanic/Latino Populations: Applications in the Hispanic Community Health Study/Study of Latinos

    PubMed Central

    Conomos, Matthew P.; Laurie, Cecelia A.; Stilp, Adrienne M.; Gogarten, Stephanie M.; McHugh, Caitlin P.; Nelson, Sarah C.; Sofer, Tamar; Fernández-Rhodes, Lindsay; Justice, Anne E.; Graff, Mariaelisa; Young, Kristin L.; Seyerle, Amanda A.; Avery, Christy L.; Taylor, Kent D.; Rotter, Jerome I.; Talavera, Gregory A.; Daviglus, Martha L.; Wassertheil-Smoller, Sylvia; Schneiderman, Neil; Heiss, Gerardo; Kaplan, Robert C.; Franceschini, Nora; Reiner, Alex P.; Shaffer, John R.; Barr, R. Graham; Kerr, Kathleen F.; Browning, Sharon R.; Browning, Brian L.; Weir, Bruce S.; Avilés-Santa, M. Larissa; Papanicolaou, George J.; Lumley, Thomas; Szpiro, Adam A.; North, Kari E.; Rice, Ken; Thornton, Timothy A.; Laurie, Cathy C.

    2016-01-01

    US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness. PMID:26748518

  7. An in-depth analysis identifies two new independent signals in 11q23.3 associated with vitiligo in the Chinese Han population.

    PubMed

    Zhao, Suli; Fang, Fang; Tang, Xianfa; Dou, Jinfa; Wang, Wenjun; Zheng, Xiaodong; Sun, Liangdan; Zhang, Anping

    2017-10-01

    Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92×10 -3 (0.05/26) was considered statistically significant. The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR=1.21, 95% CI: 1.11-1.31, P=1.20×10 -5 ; OR=1.14, 95% CI: 1.07-1.23, P=1.90×10 -4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR=1.25, 95% CI: 1.12-1.38, P=3.04×10 -5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P=7.00×10 -6 , rs523604: P=4.00×10 -3 , rs638893: P=1.20×10 -5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  8. Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

    PubMed Central

    Calaza, Manuel; Witte, Torsten; Papasteriades, Chryssa; Marchini, Maurizio; Migliaresi, Sergio; Kovacs, Attila; Ordi-Ros, Josep; Bijl, Marc; Santos, Maria Jose; Ruzickova, Sarka; Pullmann, Rudolf; Carreira, Patricia; Skopouli, Fotini N.; D'Alfonso, Sandra; Sebastiani, Gian Domenico; Suarez, Ana; Blanco, Francisco J.; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested. PMID:22194982

  9. The Oriental Fruit Fly, Bactrocera dorsalis, in China: Origin and Gradual Inland Range Expansion Associated with Population Growth

    PubMed Central

    Wan, Xuanwu; Nardi, Francesco; Zhang, Bin; Liu, Yinghong

    2011-01-01

    The oriental fruit fly, Bactrocera dorsalis, expanded throughout mainland China in the last century to become one of the most serious pests in the area, yet information on this process are fragmentary. Three mitochondrial genes (nad1, cytb and nad5) were used to infer the genetic diversity, population structure and demographic history of the oriental fruit fly from its entire distribution range in China. High levels of genetic diversity, as well as a significant correspondence between genetic and geographic distances, suggest that the invasion process might have been gradual, with no associated genetic bottlenecks. Three population groups could be identified, nevertheless the overall genetic structure was weak. The effective number of migrants between populations, estimated using the coalescent method, suggested asymmetric gene flow from the costal region of Guangdong to most inland regions. The demographic analysis indicates the oriental fruit fly underwent a recent population expansion in the Central China. We suggest the species originated in the costal region facing the South China Sea and gradually expanded to colonize mainland China, expanding here to high population numbers. PMID:21984907

  10. The oriental fruit fly, Bactrocera dorsalis, in China: origin and gradual inland range expansion associated with population growth.

    PubMed

    Wan, Xuanwu; Nardi, Francesco; Zhang, Bin; Liu, Yinghong

    2011-01-01

    The oriental fruit fly, Bactrocera dorsalis, expanded throughout mainland China in the last century to become one of the most serious pests in the area, yet information on this process are fragmentary. Three mitochondrial genes (nad1, cytb and nad5) were used to infer the genetic diversity, population structure and demographic history of the oriental fruit fly from its entire distribution range in China. High levels of genetic diversity, as well as a significant correspondence between genetic and geographic distances, suggest that the invasion process might have been gradual, with no associated genetic bottlenecks. Three population groups could be identified, nevertheless the overall genetic structure was weak. The effective number of migrants between populations, estimated using the coalescent method, suggested asymmetric gene flow from the costal region of Guangdong to most inland regions. The demographic analysis indicates the oriental fruit fly underwent a recent population expansion in the Central China. We suggest the species originated in the costal region facing the South China Sea and gradually expanded to colonize mainland China, expanding here to high population numbers.

  11. Higher risk for thyroid diseases in physicians than in the general population: a Taiwan nationwide population-based secondary analysis study.

    PubMed

    Chen, T-Y; Hsu, C-C; Feng, I-J; Wang, J-J; Su, S-B; Guo, H-R; Huang, C-C; Lin, H-J

    2017-03-01

    Physicians have high work stress, responsibility for night shifts and chances of exposure to medical radiation, which may increase the risk for thyroid diseases. We conducted this study to assess the risk for thyroid diseases in physicians, which remain unclear. We used a secondary analysis of the Taiwan National Health Insurance Research Database for this study. After excluding thyroid diseases occurring before 2006 and residents, physicians and general population were identified by matching with age and sex in 2009 in a 1:2 ratio. The risk for thyroid diseases was compared between the physicians and general population and among physicians by tracing their medical histories between 2006 and 2012. In total, 28,649 physicians and 57,298 general population were identified. Physicians had a higher risk for overall thyroid diseases than the general population [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.10-1.47], including individual thyroid disease: thyroid cancer (OR: 1.89; 95% CI: 1.22-2.95), hypothyroidism (OR: 1.64; 95% CI: 1.23-2.18) and thyroiditis (OR: 1.48; 95% CI: 1.00-2.19). We showed that physicians had a significantly higher risk for thyroid diseases than the general population. This reminds us to pay more attention to thyroid diseases in physicians. Further studies about the underlying mechanisms are warranted. © The Author 2016. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  12. Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population.

    PubMed

    Li, Libo; Lan, Xiaolin

    2016-12-01

    To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case-control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test. Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27-71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20-3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58-18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma. For Chinese population, HBV, HCV or HBV/HCV double infection can

  13. Eating Behaviour in the General Population: An Analysis of the Factor Structure of the German Version of the Three-Factor-Eating-Questionnaire (TFEQ) and Its Association with the Body Mass Index

    PubMed Central

    Löffler, Antje; Luck, Tobias; Then, Francisca S.; Sikorski, Claudia; Kovacs, Peter; Böttcher, Yvonne; Breitfeld, Jana; Tönjes, Anke; Horstmann, Annette; Löffler, Markus; Engel, Christoph; Thiery, Joachim; Villringer, Arno; Stumvoll, Michael; Riedel-Heller, Steffi G.

    2015-01-01

    The Three-Factor-Eating-Questionnaire (TFEQ) is an established instrument to assess eating behaviour. Analysis of the TFEQ-factor structure was based on selected, convenient and clinical samples so far. Aims of this study were (I) to analyse the factor structure of the German version of the TFEQ and (II)—based on the refined factor structure—to examine the association between eating behaviour and the body mass index (BMI) in a general population sample of 3,144 middle-aged and older participants (40–79 years) of the ongoing population based cohort study of the Leipzig Research Center for Civilization Diseases (LIFE Health Study). The factor structure was examined in a split-half analysis with both explorative and confirmatory factor analysis. Associations between TFEQ-scores and BMI values were tested with multiple regression analyses controlled for age, gender, and education. We found a three factor solution for the TFEQ with an ‘uncontrolled eating’, a ‘cognitive restraint’ and an ‘emotional eating’ domain including 29 of the original 51 TFEQ-items. Scores of the ‘uncontrolled eating domain’ showed the strongest correlation with BMI values (partial r = 0.26). Subjects with scores above the median in both ‘uncontrolled eating’ and ‘emotional eating’ showed the highest BMI values (mean = 29.41 kg/m²), subjects with scores below the median in all three domains showed the lowest BMI values (mean = 25.68 kg/m²; F = 72.074, p<0.001). Our findings suggest that the TFEQ is suitable to identify subjects with specific patterns of eating behaviour that are associated with higher BMI values. Such information may help health care professionals to develop and implement more tailored interventions for overweight and obese individuals. PMID:26230264

  14. Biases and regularities of grapheme-colour associations in Japanese nonsynaesthetic population.

    PubMed

    Nagai, Jun-ichi; Yokosawa, Kazuhiko; Asano, Michiko

    2016-01-01

    Associations between graphemes and colours in a nonsynaesthetic Japanese population were investigated. Participants chose the most suitable colour from 11 basic colour terms for each of 40 graphemes from the four categories of graphemes used in the Japanese language (kana characters, English alphabet letters, and Arabic and kanji numerals). This test was repeated after a three-week interval. In their responses, which were not as temporally consistent as those of grapheme-colour synaesthetes, participants showed biases and regularities that were comparable to those of synaesthetes reported in past studies. Although it has been believed that only synaesthetes, and not nonsynaesthetes, tended to associate graphemes with colours based on grapheme frequency, Berlin and Kay's colour typology, and colour word frequency, participants in this study tended in part to associate graphemes with colours based on the above factors. Moreover, participants that were nonsynaesthetes tended to associate different graphemes that shared sounds and/or meanings (e.g., Arabic and kanji numerals representing the same number) with the same colours, which was analogous to the findings in Japanese synaesthetes. These results support the view that grapheme-colour synaesthesia might have its origins in cross-modal association processes that are shared with the general population.

  15. The association between Internet addiction and personality disorders in a general population-based sample.

    PubMed

    Zadra, Sina; Bischof, Gallus; Besser, Bettina; Bischof, Anja; Meyer, Christian; John, Ulrich; Rumpf, Hans-Jürgen

    2016-12-01

    Background and aims Data on Internet addiction (IA) and its association with personality disorder are rare. Previous studies are largely restricted to clinical samples and insufficient measurement of IA. Methods Cross-sectional analysis data are based on a German sub-sample (n = 168; 86 males; 71 meeting criteria for IA) with increased levels of excessive Internet use derived from a general population sample (n = 15,023). IA was assessed with a comprehensive standardized interview using the structure of the Composite International Diagnostic Interview and the criteria of Internet Gaming Disorder as suggested in DSM-5. Impulsivity, attention deficit hyperactivity disorder, and self-esteem were assessed with the widely used questionnaires. Results Participants with IA showed higher frequencies of personality disorders (29.6%) compared to those without IA (9.3%; p < .001). In males with IA, Cluster C personality disorders were more prevalent than among non-addicted males. Compared to participants who had IA only, lower rates of remission of IA were found among participants with IA and additional cluster B personality disorder. Personality disorders were significantly associated with IA in multivariate analysis. Comorbidity of IA and personality disorders must be considered in prevention and treatment.

  16. Prevalence of traumatic brain injury in intimate partner violence offenders compared to the general population: a meta-analysis.

    PubMed

    Farrer, Thomas J; Frost, R Brock; Hedges, Dawson W

    2012-04-01

    Intimate partner violence (IPV) is widespread. Several risk factors are associated with IPV perpetuation, including alcohol use and educational level. The aggression and violence associated with traumatic brain injury (TBI) suggest that brain trauma may also be a risk factor for IPV. To examine the association between TBI and IPV, the authors conducted a meta-analysis of peer-reviewed published studies reporting the prevalence of TBI in IPV perpetrators. The authors compared the frequency of TBI among IPV perpetuators to estimates of TBI in the general population using a single-sample test of proportions. Six studies containing a total of 222 subjects met inclusion criteria. Fifty-three percent (119) of the IPV perpetuators had a history of TBI, a prevalence significantly higher (p < .0001) than estimates of TBI in the general population. The prevalence of TBI among perpetuators of IPV appears significantly higher than the prevalence of TBI in the general population. To the extent that this association is causal, TBI may be a risk factor for interpersonal violence, although comparatively few source studies, lack of standardized information about TBI severity, and the inability to investigate potential confounding variables necessarily limit this conclusion.

  17. Saturated fat intake modulates the association between an obesity genetic risk score and body mass index in two US populations.

    PubMed

    Casas-Agustench, Patricia; Arnett, Donna K; Smith, Caren E; Lai, Chao-Qiang; Parnell, Laurence D; Borecki, Ingrid B; Frazier-Wood, Alexis C; Allison, Matthew; Chen, Yii-Der Ida; Taylor, Kent D; Rich, Stephen S; Rotter, Jerome I; Lee, Yu-Chi; Ordovás, José M

    2014-12-01

    Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and body mass index (BMI) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) population, focusing on gene-diet interactions with total fat and saturated fatty acid (SFA) intake, and to replicate findings in the Multi-Ethnic Study of Atherosclerosis (MESA) population. Cross-sectional analyses included 783 white US participants from GOLDN and 2,035 from MESA. Dietary intakes were estimated with validated food frequency questionnaires. Height and weight were measured. A weighted GRS was calculated on the basis of 63 obesity-associated variants. Multiple linear regression models adjusted by potential confounders were used to examine gene-diet interactions between dietary intake (total fat and SFA) and the obesity GRS in determining BMI. Significant interactions were found between total fat intake and the obesity GRS using these variables as continuous for BMI (P for interaction=0.010, 0.046, and 0.002 in GOLDN, MESA, and meta-analysis, respectively). These association terms were stronger when assessing interactions between SFA intake and GRS for BMI (P for interaction=0.005, 0.018, and <0.001 in GOLDN, MESA, and meta-analysis, respectively). SFA intake interacts with an obesity GRS in modulating BMI in two US populations. Although determining the causal direction requires further investigation, these findings suggest that potential dietary recommendations to reduce BMI effectively in populations with high obesity GRS would be to reduce total fat intake mainly by limiting SFAs. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights

  18. First molecular genotyping of insensitive acetylcholinesterase associated with malathion resistance in Culex quinquefasciatus Say populations in Malaysia.

    PubMed

    Low, Van Lun; Chen, Chee Dhang; Lim, Phaik Eem; Lee, Han Lim; Lim, Yvonne Ai Lian; Tan, Tiong Kai; Sofian-Azirun, Mohd

    2013-12-01

    Given that there is limited available information on the insensitive acetylcholinesterase in insect species in Malaysia, the present study aims to detect the presence of G119S mutation in the acetylcholinesterase gene of Culex quinquefasciatus from 14 residential areas across 13 states and a federal territory in Malaysia. The ace-1 sequence and PCR-RFLP test revealed the presence of glycine-serine ace-1 mutation in the wild populations of Cx. quinquefasciatus. Both direct sequencing and PCR-RFLP methods demonstrated similar results and revealed the presence of a heterozygous genotype at a very low frequency (18 out of 140 individuals), while a homozygous resistant genotype was not detected across any study site in Malaysia. In addition, statistical analysis also revealed that malathion resistance is associated with the frequency of ace-1(R) in Cx. quinquefasciatus populations. This study has demonstrated the first field-evolved instance of G119S mutation in Malaysian populations. Molecular identification of insensitive acetylcholinesterase provides significant insights into the evolution and adaptation of the Malaysian Cx. quinquefasciatus populations. © 2013 Society of Chemical Industry.

  19. Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population.

    PubMed

    Lai, Yau-Huei; Yun, Chun-Ho; Su, Cheng-Huang; Yang, Fei-Shih; Yeh, Hung-I; Hou, Charles Jia-Yin; Wu, Tung-Hsin; Cury, Ricardo C; Bezerra, Hiram G; Hung, Chung-Lieh

    2016-03-01

    Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population. © 2016 The authors.

  20. Green tea and liver cancer risk: A meta-analysis of prospective cohort studies in Asian populations.

    PubMed

    Huang, Ya-Qing; Lu, Xin; Min, Han; Wu, Qian-Qian; Shi, Xiao-Ting; Bian, Kang-Qi; Zou, Xiao-Ping

    2016-01-01

    The aim of this meta-analysis was to investigate whether an association existed between green tea consumption and the risk for liver cancer in prospective cohort studies in Asian populations. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science, and the Chinese Bio-medicine Database published before April 2015. Study-specific risk estimates for the highest versus non- or lowest and increment of daily cup of green tea consumption levels were combined based on fixed- or random-effects models. STATA 11.0 (Stata Corporation, College Station, TX, USA) software was used for statistical analysis. Nine prospective cohort articles involving 465,274 participants and 3694 cases of liver cancer from China, Japan, and Singapore were included. The summary relative risk (RR) indicated a significant association between the highest green tea consumption and reduced risk for liver cancer (summary RR, 0.88; 95% confidence interval [CI], 0.81-0.97). However, no statistically significant association was observed when analyzing daily consumption of one cup (summary RR, 0.97; 95% CI, 0.95-1.00). When stratified by sex, the protective effect of green tea consumption on risk for liver cancer was observed only in the group of women (summary RR, 0.78; 95% CI, 0.64-0.96), but not in men (summary RR, 0.89; 95% CI, 0.79-1.00). The present analysis indicated the preventive effects of green tea intake on the risk for liver cancer in female Asian populations. However, additional studies are needed to make a convincing case for this association. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Impact of obesity-related genes in Spanish population

    PubMed Central

    2013-01-01

    Background The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Results Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). Conclusion The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population. PMID:24267414

  2. Impact of obesity-related genes in Spanish population.

    PubMed

    Martínez-García, Fernando; Mansego, María L; Rojo-Martínez, Gemma; De Marco-Solar, Griselda; Morcillo, Sonsoles; Soriguer, Federico; Redón, Josep; Pineda Alonso, Monica; Martín-Escudero, Juan C; Cooper, Richard S; Chaves, Felipe J

    2013-11-23

    The objective was to investigate the association between BMI and single nucleotide polymorphisms previously identified of obesity-related genes in two Spanish populations. Forty SNPs in 23 obesity-related genes were evaluated in a rural population characterized by a high prevalence of obesity (869 subjects, mean age 46 yr, 62% women, 36% obese) and in an urban population (1425 subjects, mean age 54 yr, 50% women, 19% obese). Genotyping was assessed by using SNPlex and PLINK for the association analysis. Polymorphisms of the FTO were significantly associated with BMI, in the rural population (beta 0.87, p-value <0.001). None of the other SNPs showed significant association after Bonferroni correction in the two populations or in the pooled analysis. A weighted genetic risk score (wGRS) was constructed using the risk alleles of the Tag-SNPs with a positive Beta parameter in both populations. From the first to the fifth quintile of the score, the BMI increased 0.45 kg/m2 in Hortega and 2.0 kg/m2 in Pizarra. Overall, the obesity predictive value was low (less than 1%). The risk associated with polymorphisms is low and the overall effect on BMI or obesity prediction is minimal. A weighted genetic risk score based on genes mainly acting through central nervous system mechanisms was associated with BMI but it yields minimal clinical prediction for the obesity risk in the general population.

  3. Population subdivision and molecular sequence variation: theory and analysis of Drosophila ananassae data.

    PubMed

    Vogl, Claus; Das, Aparup; Beaumont, Mark; Mohanty, Sujata; Stephan, Wolfgang

    2003-11-01

    Population subdivision complicates analysis of molecular variation. Even if neutrality is assumed, three evolutionary forces need to be considered: migration, mutation, and drift. Simplification can be achieved by assuming that the process of migration among and drift within subpopulations is occurring fast compared to mutation and drift in the entire population. This allows a two-step approach in the analysis: (i) analysis of population subdivision and (ii) analysis of molecular variation in the migrant pool. We model population subdivision using an infinite island model, where we allow the migration/drift parameter Theta to vary among populations. Thus, central and peripheral populations can be differentiated. For inference of Theta, we use a coalescence approach, implemented via a Markov chain Monte Carlo (MCMC) integration method that allows estimation of allele frequencies in the migrant pool. The second step of this approach (analysis of molecular variation in the migrant pool) uses the estimated allele frequencies in the migrant pool for the study of molecular variation. We apply this method to a Drosophila ananassae sequence data set. We find little indication of isolation by distance, but large differences in the migration parameter among populations. The population as a whole seems to be expanding. A population from Bogor (Java, Indonesia) shows the highest variation and seems closest to the species center.

  4. Physiogenomic analysis of the Puerto Rican population.

    PubMed

    Ruaño, Gualberto; Duconge, Jorge; Windemuth, Andreas; Cadilla, Carmen L; Kocherla, Mohan; Villagra, David; Renta, Jessica; Holford, Theodore; Santiago-Borrero, Pedro J

    2009-04-01

    Admixture in the population of the island of Puerto Rico is of general interest with regards to pharmacogenetics to develop comprehensive strategies for personalized healthcare in Latin Americans. This research was aimed at determining the frequencies of SNPs in key physiological, pharmacological and biochemical genes to infer population structure and ancestry in the Puerto Rican population. A noninterventional, cross-sectional, retrospective study design was implemented following a controlled, stratified-by-region, random sampling protocol. The sample was based on birthrates in each region of the island of Puerto Rico, according to the 2004 National Birth Registry. Genomic DNA samples from 100 newborns were obtained from the Puerto Rico Newborn Screening Program in dried-blood spot cards. Genotyping using a physiogenomic array was performed for 332 SNPs from 196 cardiometabolic and neuroendocrine genes. Population structure was examined using a Bayesian clustering approach as well as by allelic dissimilarity as a measure of allele sharing. The Puerto Rican sample was found to be broadly heterogeneous. We observed three main clusters in the population, which we hypothesize to reflect the historical admixture in the Puerto Rican population from Amerindian, African and European ancestors. We present evidence for this interpretation by comparing allele frequencies for the three clusters with those for the same SNPs available from the International HapMap project for Asian, African and European populations. Our results demonstrate that population analysis can be performed with a physiogenomic array of cardiometabolic and neuroendocrine genes to facilitate the translation of genome diversity into personalized medicine.

  5. Physiogenomic analysis of the Puerto Rican population

    PubMed Central

    Ruaño, Gualberto; Duconge, Jorge; Windemuth, Andreas; Cadilla, Carmen L; Kocherla, Mohan; Villagra, David; Renta, Jessica; Holford, Theodore; Santiago-Borrero, Pedro J

    2009-01-01

    Aims Admixture in the population of the island of Puerto Rico is of general interest with regards to pharmacogenetics to develop comprehensive strategies for personalized healthcare in Latin Americans. This research was aimed at determining the frequencies of SNPs in key physiological, pharmacological and biochemical genes to infer population structure and ancestry in the Puerto Rican population. Materials & methods A noninterventional, cross-sectional, retrospective study design was implemented following a controlled, stratified-by-region, random sampling protocol. The sample was based on birthrates in each region of the island of Puerto Rico, according to the 2004 National Birth Registry. Genomic DNA samples from 100 newborns were obtained from the Puerto Rico Newborn Screening Program in dried-blood spot cards. Genotyping using a physiogenomic array was performed for 332 SNPs from 196 cardiometabolic and neuroendocrine genes. Population structure was examined using a Bayesian clustering approach as well as by allelic dissimilarity as a measure of allele sharing. Results The Puerto Rican sample was found to be broadly heterogeneous. We observed three main clusters in the population, which we hypothesize to reflect the historical admixture in the Puerto Rican population from Amerindian, African and European ancestors. We present evidence for this interpretation by comparing allele frequencies for the three clusters with those for the same SNPs available from the International HapMap project for Asian, African and European populations. Conclusion Our results demonstrate that population analysis can be performed with a physiogenomic array of cardiometabolic and neuroendocrine genes to facilitate the translation of genome diversity into personalized medicine. PMID:19374515

  6. Analysis of iris surface features in populations of diverse ancestry

    PubMed Central

    Edwards, Melissa; Cha, David; Krithika, S.; Johnson, Monique; Parra, Esteban J.

    2016-01-01

    There are many textural elements that can be found in the human eye, including Fuchs’ crypts, Wolfflin nodules, pigment spots, contraction furrows and conjunctival melanosis. Although iris surface features have been well-studied in populations of European ancestry, the worldwide distribution of these traits is poorly understood. In this paper, we develop a new method of characterizing iris features from photographs of the iris. We then apply this method to a diverse sample of East Asian, European and South Asian ancestry. All five iris features showed significant differences in frequency between the three populations, indicating that iris features are largely population dependent. Although none of the features were correlated with each other in the East and South Asian groups, Fuchs’ crypts were significantly correlated with contraction furrows and pigment spots and contraction furrows were significantly associated with pigment spots in the European group. The genetic marker SEMA3A rs10235789 was significantly associated with Fuchs’ crypt grade in the European, East Asian and South Asian samples and a borderline association between TRAF3IP1 rs3739070 and contraction furrow grade was found in the European sample. The study of iris surface features in diverse populations may provide valuable information of forensic, biomedical and ophthalmological interest. PMID:26909168

  7. The Association Between Body Mass Index and Open-angle Glaucoma in a South Korean Population-based Sample.

    PubMed

    Lin, Shuai-Chun; Pasquale, Louis R; Singh, Kuldev; Lin, Shan C

    2018-03-01

    The purpose of this article is to investigate the association between body mass index (BMI) and open-angle glaucoma (OAG) in a sample of the South Korean population. The sample consisted of a cross-sectional, population-based sample of 10,978 participants, 40 years of age and older, enrolled in the 2008 to 2011 Korean National Health and Nutrition Examination Survey. All participants had measured intraocular pressure <22 mm Hg and open anterior chamber angles. OAG was defined using disc and visual field criteria established by the International Society for Geographical and Epidemiological Ophthalmology. Multivariable analyses were performed to determine the association between BMI and OAG. These analyses were also performed in a sex-stratified and age-stratified manner. After adjusting for potential confounding variables, lower BMI (<19 kg/m) was associated with greater risk of OAG compared with normal BMI (19 to 24.9 kg/m) [odds ratio (OR), 2.28; 95% confidence interval (CI), 1.22-4.26]. In sex-stratified analyses, low BMI remained adversely related to glaucoma in women (OR, 3.45; 95% CI, 1.42-8.38) but not in men (OR, 1.72; 95% CI, 0.71-4.20). In age-stratified analyses, lower BMI was adversely related to glaucoma among subjects 40- to 49-year old (OR, 5.16; 95% CI, 1.86-14.36) but differences in glaucoma prevalence were not statistically significant between those with low versus normal BMI in other age strata. Lower BMI was associated with increased odds of OAG in a sample of the South Korean population. Multivariate analysis revealed the association to be statistically significant in women and those in the youngest age stratum.

  8. A genome-wide association study of limb bone length using a Large White × Minzhu intercross population.

    PubMed

    Zhang, Long-Chao; Li, Na; Liu, Xin; Liang, Jing; Yan, Hua; Zhao, Ke-Bin; Pu, Lei; Shi, Hui-Bi; Zhang, Yue-Bo; Wang, Li-Gang; Wang, Li-Xian

    2014-11-04

    In pig, limb bone length influences ham yield and body height to a great extent and has important economic implications for pig industry. In this study, an intercross population was constructed between the indigenous Chinese Minzhu pig breed and the western commercial Large White pig breed to examine the genetic basis for variation in limb bone length. The aim of this study was to detect potential genetic variants associated with porcine limb bone length. A total of 571 F2 individuals from a Large White and Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for femur length (FL), humerus length (HL), hipbone length (HIPL), scapula length (SL), tibia length (TL), and ulna length (UL). A genome-wide association study was performed by applying the previously reported approach of genome-wide rapid association using mixed model and regression. Statistical significance of the associations was based on Bonferroni-corrected P-values. A total of 39 significant SNPs were mapped to a 11.93 Mb long region on pig chromosome 7 (SSC7). Linkage analysis of these significant SNPs revealed three haplotype blocks of 495 kb, 376 kb and 492 kb, respectively, in the 11.93 Mb region. Annotation based on the pig reference genome identified 15 genes that were located near or contained the significant SNPs in these linkage disequilibrium intervals. Conditioned analysis revealed that four SNPs, one on SSC2 and three on SSC4, showed significant associations with SL and HL, respectively. Analysis of the 15 annotated genes that were identified in these three haplotype blocks indicated that HMGA1 and PPARD, which are expressed in limbs and influence chondrocyte cell growth and differentiation, could be considered as relevant biological candidates for limb bone length in pig, with potential applications in breeding programs. Our results may also be useful for the study of the mechanisms that underlie human limb length and body height.

  9. Identification of three novel loci of ALDH2 Gene for Serum Folate levels in a Male Chinese Population by Genome-Wide Association Study.

    PubMed

    Deng, Caiwang; Tang, Shaomei; Huang, Xiaoliang; Gao, Jiamin; Tian, Jiarong; Zhou, Xianguo; Xie, Yuanliang; Liao, Ming; Mo, Zengnan; Wang, Qiuyan

    2018-06-25

    Serum folate is important in clinical researches and DNA synthesis and methylation. Some loci and genes that are associated with folate levels had been detected by genome-wide association studies (GWAS), such as rs1801133 in MTHFR and rs1979277 in SHMT1. Nevertheless, only a small part of variants has been clearly identified for serum folate. Hence, we conducted a GWAS to discover new inherited susceptibility and gene-environment interactions on serum folate concentration. In a healthy Chinese population of 1999 men, genotyping was performed using Illumina HumanOmni1-Quad BeadChip. Serum folate levels were measured by enzyme-linked immunosorbent assay (ELISA), pathway enrichment analysis and statistical analysis were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID) and Statistic Package for Social Science (SPSS). We validated that rs1801133 in MTHFR was significantly involved in serum folate (P = 4.21 × 10 -19 ). Surprisingly, we discovered three novel loci rs3782886, rs671, and rs4646776 of ALDH2 gene were suggestively significantly associated with folate serum folate levels in the male population studied (P = 2.17 × 10 -7 , P = 3.60 × 10 -7 , P = 3.99 × 10 -7 , respectively) after adjusting for population stratification, BMI and age. Men with the AA genotype had significantly higher serum folate levels compared with men with the GG/AG genotype. But we found ALDH2 gene mutation no relation to part of environmental factors on serum folate levels. In a male Chinese population, genome-wide association study discovered that three novel SNPs rs3782886, rs671 and rs4646776 of ALDH2 gene were suggestively significantly associated with serum folate levels. Copyright © 2018. Published by Elsevier B.V.

  10. Using Christmas Bird Count data in analysis of population change

    USGS Publications Warehouse

    Sauer, J.R.; Link, W.A.

    2002-01-01

    The scientific credibility of Christmas Bird Count (CBC) results depend on the development and implementation of appropriate methods of statistical analysis. The key to any successful analysis of CBC data is to begin with a careful review of how the limitations of the data are likely to influence the results of the analysis, then to choose methods of analysis that accommodate as much as possible the limitations of the survey. For our analyses of CBC data, we develop a flexible model for effort adjustment and use information from the data to guide the selection of the best model. We include geographic structuring to accommodate the regional variation in number of samples, use a model that allows for overdispersed poisson data appropriate for counts, and employ empirical Bayes procedures to accommodate differences in quality of information in regional summaries. This generalized linear model approach is very flexible, and can be applied to a variety of studies focused on factors influencing wintering bird populations. In particular, the model can be easily modified to contain covariates, allowing for assessment of associations between CBC counts and winter weather, disturbance, and a variety of other environmental factors. These new survey analysis methods have added value in that they provide insights into changes in survey design that can enhance the value of the information. The CBC has been extremely successful as a tool for increasing public interest in birding and bird conservation. Use of the information for bird conservation creates new demands on quality of information, and it is important to maintain a dialogue between users of the information, information needs for the analyses, and survey coordinators and participants. Our work as survey analysts emphasizes the value and limitations of existing data, and provides some indications of what features of the survey could be modified to make the survey a more reliable source of bird population data. Surveys

  11. Population Viability Analysis of Riverine Fishes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bates, P.; Chandler, J.; Jager, H.I.

    Many utilities face conflkts between two goals: cost-efficient hydropower generation and protecting riverine fishes. Research to develop ecological simulation tools that can evaluate alternative mitigation strategies in terms of their benefits to fish populations is vital to informed decision-making. In this paper, we describe our approach to population viability analysis of riverine fishes in general and Snake River white sturgeon in particular. We are finding that the individual-based modeling approach used in previous in-stream flow applications is well suited to addressing questions about the viability of species of concern for several reasons. Chief among these are: (1) the abiIity tomore » represent the effects of individual variation in life history characteristics on predicted population viabili~, (2) the flexibili~ needed to quanti~ the ecological benefits of alternative flow management options by representing spatial and temporal variation in flow and temperaturty and (3) the flexibility needed to quantifi the ecological benefits of non-flow related manipulations (i.e., passage, screening and hatchery supplementation).« less

  12. Bronchiectasis-Associated Hospitalizations in Germany, 2005–2011: A Population-Based Study of Disease Burden and Trends

    PubMed Central

    Ringshausen, Felix C.; de Roux, Andrés; Pletz, Mathias W.; Hämäläinen, Nina; Welte, Tobias; Rademacher, Jessica

    2013-01-01

    Background Representative population-based data on the epidemiology of bronchiectasis in Europe are limited. The aim of the present study was to investigate the current burden and the trends of bronchiectasis-associated hospitalizations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources. Methods The nationwide diagnosis-related groups hospital statistics for the years 2005–2011 were used in order to identify hospitalizations with bronchiectasis as any hospital discharge diagnosis according to the International Classification of Diseases, 10th revision, code J47, (acquired) bronchiectasis. Poisson log-linear regression analysis was used to assess the significance of trends. In addition, the overall length of hospital stay (LOS) and the in-hospital mortality in comparison to the nationwide overall mortality due to bronchiectasis as the primary diagnosis was assessed. Results Overall, 61,838 records with bronchiectasis were extracted from more than 125 million hospitalizations. The average annual age-adjusted rate for bronchiectasis as any diagnosis was 9.4 hospitalizations per 100,000 population. Hospitalization rates increased significantly during the study period, with the highest rate of 39.4 hospitalizations per 100,000 population among men aged 75–84 years and the most pronounced average annual increases among females. Besides numerous bronchiectasis-associated conditions, chronic obstructive pulmonary disease (COPD) was most frequently found in up to 39.2% of hospitalizations with bronchiectasis as the primary diagnosis. The mean LOS was comparable to that for COPD. Overall, only 40% of bronchiectasis-associated deaths occurred inside the hospital. Conclusions The present study provides evidence of a changing epidemiology and a steadily increasing prevalence of bronchiectasis-associated hospitalizations. Moreover, it confirms the diversity of bronchiectasis-associated

  13. Transformation of a cadaver population: Analysis of a South African cadaver program, 1921-2013.

    PubMed

    Kramer, Beverley; Hutchinson, Erin F

    2015-01-01

    Anatomy has served as a cornerstone in the training of various allied and clinical disciplines and has traditionally been based on dissection of the human body. Thus, to pursue this method of teaching and learning, access to cadavers is of continuing importance. Over a significant period of time unclaimed cadavers have performed an essential role in the teaching of anatomy in South Africa and in Africa. As recent cadaver numbers were declining at the School of Anatomical Sciences, University of the Witwatersrand, Johannesburg and difficulty in procurement was being experienced, the purpose of this study was to critically evaluate the composition of our cadaver population over time so as to provide possible strategies to arrest the decline. A retrospective, quantitative analysis of cadaver records from the School of Anatomical Sciences between 1921 and 2013 was undertaken. Analysis included a comparison of Poisson counts and Fischer's exact test. A significant decrease in the number of cadavers received during the period 2000-2013 and a slow bequest program over the same period of time has led to concerns about the sustainability of teaching anatomy through dissection. Decreases in the numbers of males and cadavers of the black population group occurred between 1990 and 2013, and of bequests from 2000 to 2013. An influence on the cadaver population from a changing political climate and change in socioeconomic status of part of the population was perceived. Changes in sex and population group of the cadavers may have a long-term effect on teaching and research. © 2014 American Association of Anatomists.

  14. Identifying the association between interleukin-6 and lichen planus: A meta-analysis

    PubMed Central

    Yin, Meng; Li, Guifeng; Song, Hui; Lin, Song

    2017-01-01

    Numerous studies have examined the association between interleukin-6 and the pathogenesis of lichen planus (LP)/oral LP (OLP) in various populations; however, there is a lack of systematic analysis. The aim of the present study was to assess this association more precisely, thus a meta-analysis was performed. Case-control studies, which were published up to December 2015, were obtained from PubMed, Embase and the China National Knowledge Infrastructure databases. Data were extracted and pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Ultimately, eight studies were included, comprising 299 LP/OLP cases and 231 control subjects. Overall, the pooled MD for IL-6 was 16.24 (95% CI, 9.84–22.64; I2=99% for heterogeneity). In the subgroup analysis by ethnicity, a significant increase of the IL-6 expression level was identified among Asian individuals, but not in Caucasian individuals. Thus, IL-6 may be significant in the pathogenesis of LP. However, further studies are required to validate these associations. PMID:28529737

  15. Association Between Elder Self-Neglect and Hospice Utilization in a Community Population

    PubMed Central

    Dong, XinQi; Simon, Melissa A.

    2012-01-01

    Elder self-neglect is associated with substantial 1-year mortality. However, hospice utilization among those with self-neglect remain unclear. The objective of this study is to quantify the prospective relation between self-neglect and risk for hospice utilization in a community population of older adults. Prospective population-based study in a geographically-defined community in Chicago of older adults who participated in the Chicago Health and Aging Project. Of the 8,669 participants in the Chicago Health and Aging Project, a subset of 1,438 participants was reported to social services agency for suspected elder self-neglect. Outcome of interest was the hospice utilization obtained from the Center for Medicare and Medicaid System. Cox proportional hazard models were used to assess independent association of self-neglect with risk of hospice utilization using time-varying covariate analyses. After adjusting for potential confounding factors, elders who self-neglect was associated with increased risk for hospice utilization (HR, 2.43, 95% CI, 2.10-2.81). Greater self-neglect severity (Mild: (HR, 2.12 (1.61-2.79); Moderate: (HR, 2.36 (1.95-2.84); Severe: (HR, 4.66 (2.98-7.30)) were associated with increased risk for hospice utilization. Interaction term analyses suggest that the significant relationship between self-neglect and hospice utilization was not mediated through medical conditions, cognitive impairment and physical disability. Moreover, self-neglect was associated with shorter length of stay in hospice (PE, −0.27, SE, 0.12, p<0.02) and shorter time from hospice admission to death (PE, −0.32, SE, 0.13, p<0.01). Elder self-neglect was associated with increased risk of hospice use in this community population. Elder self-neglect is associated with shorter length of stay in hospice care and shorter time from hospice admission to death. PMID:22770866

  16. Association between insurance status and patient safety in the lumbar spine fusion population.

    PubMed

    Tanenbaum, Joseph E; Alentado, Vincent J; Miller, Jacob A; Lubelski, Daniel; Benzel, Edward C; Mroz, Thomas E

    2017-03-01

    Lumbar fusion is a common and costly procedure in the United States. Reimbursement for surgical procedures is increasingly tied to care quality and patient safety as part of value-based reimbursement programs. The incidence of adverse quality events among lumbar fusion patients is unknown using the definition of care quality (patient safety indicators [PSI]) used by the Centers for Medicare and Medicaid Services (CMS). The association between insurance status and the incidence of PSI is similarly unknown in lumbar fusion patients. This study sought to determine the incidence of PSI in patients undergoing inpatient lumbar fusion and to quantify the association between primary payer status and PSI in this population. A retrospective cohort study was carried out. The sample comprised all adult patients aged 18 years and older who were included in the Nationwide Inpatient Sample (NIS) that underwent lumbar fusion from 1998 to 2011. The incidence of one or more PSI, a validated and widely used metric of inpatient health-care quality and patient safety, was the primary outcome variable. The NIS data were examined for all cases of inpatient lumbar fusion from 1998 to 2011. The incidence of adverse patient safety events (PSI) was determined using publicly available lists of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Logistic regression models were used to determine the association between primary payer status (Medicaid and self-pay relative to private insurance) and the incidence of PSI. A total of 539,172 adult lumbar fusion procedures were recorded in the NIS from 1998 to 2011. Patients were excluded from the secondary analysis if "other" or "missing" was listed for primary insurance status. The national incidence of PSI was calculated to be 2,445 per 100,000 patient years of observation, or approximately 2.5%. In a secondary analysis, after adjusting for patient demographics and hospital characteristics, Medicaid

  17. Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population

    PubMed Central

    Friedrich, Deise C.; Santos, Sidney E. B.; Ribeiro-dos-Santos, Ândrea K. C.; Hutz, Mara H.

    2012-01-01

    Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The −13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The −13779*C,−13910*T, −13937*A, −14010*C, −14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was −13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The −13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the −13910*T allele is an oversimplification. PMID:23029545

  18. The associations of diastolic blood pressure with the risk of stroke in Western and Eastern populations.

    PubMed

    Ni Mhurchu, C; Rodgers, A; MacMahon, S

    1999-01-01

    This paper reviews evidence from two overviews of prospective, observational studies of the association of diastolic blood pressure (DBP) with the risk of stroke in populations from the US and Europe and populations from China and Japan. The Western overview included seven studies involving a total of 405,511 individuals. During a mean follow-up period of 11 years, 843 strokes were observed. The Eastern overview included 18 cohorts involving a total of 124,774 participants. During a mean follow-up duration of 9 years, 1,798 strokes were observed. The shape of the association between usual DBP and the risk of stroke was similar in Western and Eastern populations, but in Eastern populations the size of the association was about 50% steeper than that in Western populations. This may be due, at least in part, to cerebral haemorrhage comprising a greater proportion of total stroke in Eastern populations. This finding, together with the high stroke rates in many Eastern Asian populations, suggests that the potential benefits of blood pressure lowering may be greater in Eastern Asia.

  19. Association between unemployment, income, education level, population size and air pollution in Czech cities: evidence for environmental inequality? A pilot national scale analysis.

    PubMed

    Branis, Martin; Linhartova, Martina

    2012-09-01

    We analyzed differentials in exposure to SO(2), PM(10) and NO(2) among Czech urban populations categorized according to education level, unemployment rate, population size and average annual salary. Altogether 39 cities were included in the analysis. The principal component analysis revealed two factors explaining 72.8% of the data variability. The first factor explaining 44.7% of the data variability included SO(2), PM(10), low education level and high unemployment, documenting that inhabitants with unfavorable socioeconomic status mainly reside in smaller cities with higher concentration levels of combustion-related air pollutants. The second factor explaining 28.1% of the data variability included NO(2), high salary, high education level and large population, suggesting that large cities with residents with higher socioeconomic status are exposed to higher levels of traffic-related air pollution. We conclude that, after more than a decade of free-market economy, the Czech Republic, a former Soviet satellite with a centrally planned economy, displays signs of a certain kind of environmental inequality, since environmental hazards are unevenly distributed among the Czech urban populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Replication Study of Polymorphisms Associated With Brain Arteriovenous Malformation in a Population From South of Brazil

    PubMed Central

    Ludwig, Fernanda S; Matte, Ursula S; Mota, Simone; Stefani, Marco A

    2016-01-01

    Introduction The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. Methods We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). Results In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. Conclusions In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms. PMID:27026833