Association between rs2431697 T allele on 5q33.3 and systemic lupus erythematosus: case-control study and meta-analysis.

PubMed

Tang, Zhao-Ming; Wang, Ping; Chang, Pan-Pan; Hasahya, Tony; Xing, Hui; Wang, Jin-Ping; Hu, Li-Hua

2015-11-01

rs2431697 is located on 5q33.3, between pituitary tumor-transforming gene 1 and miR-146a. Several studies have estimated the association between rs2431697 and systemic lupus erythematosus risk. However, the results were inconsistent. A case-control study was carried out to explore the association between rs2431697 and systemic lupus erythematosus risk in a central Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. Our case-control study included 322 cases and 353 controls. rs2431697 T allele was associated with increased risk of systemic lupus erythematosus (odds ratios (ORs) = 1.461, 95% confidence intervals (CI) 1.091-1.957, P = 0.011). The association was stronger between T allele and the risk of anti-double-stranded DNA (dsDNA)-positive systemic lupus erythematosus (OR = 2.510, 95% CI 1.545-4.077, P < 0.001). The meta-analyses included 8648 systemic lupus erythematosus patients and 10947 controls. rs2431697 T allele had an overall OR of 1.262 (95% CI 1.205-1.323, P < 0.001) under fixed-effects model. After stratified by ethnicity, I (2) reduced from 24.3 to 0 %. T allele had an OR of 1.213 (95% CI 1.145-1.284, P < 0.001) in European descendant and 1.365 (95% CI 1.259-1.480, P < 0.001) in Asian under fixed-effects model. Data on women were also extracted, and T allele had an OR of 1.337 (95% CI 1.162-1.539, P < 0.001) under random-effects model. The pooled ORs were not influenced by each study in sensitivity analyses. There were no publication biases observed in these analyses. The results from our case-control study and the meta-analyses indicate that rs2431697 T allele significantly associates with the increased risk of systemic lupus erythematosus.

Associations between School-Related Factors and Depressive Symptoms among Children: A Comparative Study, Finland and Norway

ERIC Educational Resources Information Center

Minkkinen, Jaana

2014-01-01

This study compares school-related associations in depressive symptoms among children aged between 9-13 years from four schools in Finland and Norway. A total of 523 pupils participated in the cross-sectional survey. The connections between depressive symptoms and school factors were analysed using hierarchical regression analyses. School…

A Multivariate Genome-Wide Association Analysis of 10 LDL Subfractions, and Their Response to Statin Treatment, in 1868 Caucasians

PubMed Central

Shim, Heejung; Chasman, Daniel I.; Smith, Joshua D.; Mora, Samia; Ridker, Paul M.; Nickerson, Deborah A.; Krauss, Ronald M.; Stephens, Matthew

2015-01-01

We conducted a genome-wide association analysis of 7 subfractions of low density lipoproteins (LDLs) and 3 subfractions of intermediate density lipoproteins (IDLs) measured by gradient gel electrophoresis, and their response to statin treatment, in 1868 individuals of European ancestry from the Pharmacogenomics and Risk of Cardiovascular Disease study. Our analyses identified four previously-implicated loci (SORT1, APOE, LPA, and CETP) as containing variants that are very strongly associated with lipoprotein subfractions (log10Bayes Factor > 15). Subsequent conditional analyses suggest that three of these (APOE, LPA and CETP) likely harbor multiple independently associated SNPs. Further, while different variants typically showed different characteristic patterns of association with combinations of subfractions, the two SNPs in CETP show strikingly similar patterns - both in our original data and in a replication cohort - consistent with a common underlying molecular mechanism. Notably, the CETP variants are very strongly associated with LDL subfractions, despite showing no association with total LDLs in our study, illustrating the potential value of the more detailed phenotypic measurements. In contrast with these strong subfraction associations, genetic association analysis of subfraction response to statins showed much weaker signals (none exceeding log10Bayes Factor of 6). However, two SNPs (in APOE and LPA) previously-reported to be associated with LDL statin response do show some modest evidence for association in our data, and the subfraction response proles at the LPA SNP are consistent with the LPA association, with response likely being due primarily to resistance of Lp(a) particles to statin therapy. An additional important feature of our analysis is that, unlike most previous analyses of multiple related phenotypes, we analyzed the subfractions jointly, rather than one at a time. Comparisons of our multivariate analyses with standard univariate analyses demonstrate that multivariate analyses can substantially increase power to detect associations. Software implementing our multivariate analysis methods is available at http://stephenslab.uchicago.edu/software.html. PMID:25898129

Financial relationships in economic analyses of targeted therapies in oncology.

PubMed

Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

2012-04-20

A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

Pubertal timing and substance use: associations between and within families across late adolescence.

PubMed

Dick, D M; Rose, R J; Viken, R J; Kaprio, J

2000-03-01

In the present study, between-family analyses of data from adolescent twin girls offer new evidence that early menarche is associated with earlier initiation and greater frequency of smoking and drinking. The role of personality factors and peer relationships in that association was investigated, and little support was found for their involvement. Novel within-family analyses replicating associations of substance use with pubertal timing in contrasts of twin sisters selected for extreme discordance for age at menarche are reported. Within-family replications demonstrated that the association of pubertal timing with substance use cannot be explained solely by between-family confounds. Within-family analyses demonstrated contextual modulation of the influence of pubertal timing: Its impact on drinking frequency is apparent only among girls in urban settings. Sibling comparisons illustrate a promising analytic tool for studying diverse developmental outcomes.

Impact of covariate models on the assessment of the air pollution-mortality association in a single- and multipollutant context.

PubMed

Sacks, Jason D; Ito, Kazuhiko; Wilson, William E; Neas, Lucas M

2012-10-01

With the advent of multicity studies, uniform statistical approaches have been developed to examine air pollution-mortality associations across cities. To assess the sensitivity of the air pollution-mortality association to different model specifications in a single and multipollutant context, the authors applied various regression models developed in previous multicity time-series studies of air pollution and mortality to data from Philadelphia, Pennsylvania (May 1992-September 1995). Single-pollutant analyses used daily cardiovascular mortality, fine particulate matter (particles with an aerodynamic diameter ≤2.5 µm; PM(2.5)), speciated PM(2.5), and gaseous pollutant data, while multipollutant analyses used source factors identified through principal component analysis. In single-pollutant analyses, risk estimates were relatively consistent across models for most PM(2.5) components and gaseous pollutants. However, risk estimates were inconsistent for ozone in all-year and warm-season analyses. Principal component analysis yielded factors with species associated with traffic, crustal material, residual oil, and coal. Risk estimates for these factors exhibited less sensitivity to alternative regression models compared with single-pollutant models. Factors associated with traffic and crustal material showed consistently positive associations in the warm season, while the coal combustion factor showed consistently positive associations in the cold season. Overall, mortality risk estimates examined using a source-oriented approach yielded more stable and precise risk estimates, compared with single-pollutant analyses.

Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides: The GenSalt Study

PubMed Central

Li, Changwei; Bazzano, Lydia A.L.; Rao, Dabeeru C.; Hixson, James E.; He, Jiang; Gu, Dongfeng; Gu, Charles C.; Shimmin, Lawrence C.; Jaquish, Cashell E.; Schwander, Karen; Liu, De-Pei; Huang, Jianfeng; Lu, Fanghong; Cao, Jie; Chong, Shen; Lu, Xiangfeng; Kelly, Tanika N.

2016-01-01

We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log-transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms (SNPs), single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single-marker analyses within each gene using the truncated product method (TPM). Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2–2q12.1 [maximum multipoint LOD score (MML) = 2.18 at 2q11.2] and 11q24.3–11q25 (MML = 2.29 at 11q25) for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 (CHMP3), ring finger protein 103 (RNF103), AF4/FMR2 family, member 3 (AFF3), and neurotrimin (NTM ) with triglycerides (P = 4 × 10−4, 1.00 × 10−5, 2.00 × 10−5, and 1.00 × 10−7, respectively). Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants (P = 1.00 × 10−7 and 8.00 × 10−5, respectively). Furthermore, NTM explained the linkage signal on chromosome 11. In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11. PMID:25819087

Dissecting the genetics of complex traits using summary association statistics.

PubMed

Pasaniuc, Bogdan; Price, Alkes L

2017-02-01

During the past decade, genome-wide association studies (GWAS) have been used to successfully identify tens of thousands of genetic variants associated with complex traits and diseases. These studies have produced extensive repositories of genetic variation and trait measurements across large numbers of individuals, providing tremendous opportunities for further analyses. However, privacy concerns and other logistical considerations often limit access to individual-level genetic data, motivating the development of methods that analyse summary association statistics. Here, we review recent progress on statistical methods that leverage summary association data to gain insights into the genetic basis of complex traits and diseases.

Association between education and future leisure-time physical inactivity: a study of Finnish twins over a 35-year follow-up.

PubMed

Piirtola, Maarit; Kaprio, Jaakko; Kujala, Urho M; Heikkilä, Kauko; Koskenvuo, Markku; Svedberg, Pia; Silventoinen, Karri; Ropponen, Annina

2016-08-04

Education is associated with health related lifestyle choices including leisure-time physical inactivity. However, the longitudinal associations between education and inactivity merit further studies. We investigated the association between education and leisure-time physical inactivity over a 35-year follow-up with four time points controlling for multiple covariates including familial confounding. This study of the population-based Finnish Twin Cohort consisted of 5254 twin individuals born in 1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data on leisure-time physical activity and multiple covariates was available from four surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The association between years of education and leisure-time physical inactivity (<1.5 metabolic equivalent hours/day) was first analysed for each survey. Then, the role of education was investigated for 15-year and 35-year inactivity periods in the longitudinal analyses. The co-twin control design was used to analyse the potential familial confounding of the effects. All analyses were conducted with and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals (CI) were calculated using logistic and conditional (fixed-effects) regression models. Each additional year of education was associated with less inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and sex-adjusted analyses. The associations of education with inactivity in the 15- and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each year of higher education was associated with a reduced likelihood of inactivity suggesting direct effect (i.e. independent from familial confounding) of education on inactivity. However, the point estimates were lower than in the individual-level analyses. Adjustment for multiple covariates did not change these associations. Higher education is associated with lower odds of leisure-time physical inactivity during the three-decade follow-up. The association was found after adjusting for several confounders, including familial factors. Hence, the results point to the conclusion that education has an independent role in the development of long-term physical inactivity and tailored efforts to promote physical activity among lower educated people would be needed throughout adulthood.

Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

PubMed

Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

2016-09-01

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

Diabetes mellitus and arthritis: is it a risk factor or comorbidity?: A systematic review and meta-analysis.

PubMed

Dong, Qing; Liu, Hua; Yang, Daren; Zhang, Yunyan

2017-05-01

Investigators have explored the association between diabetes mellitus and arthritis for a long time; however, there are uncertainties and inconsistencies among various studies. In this study, we tried to explore the relationship between diabetes mellitus and the overall risk of arthritis, as well as the potential modifiers for this relationship. We conducted a comprehensive literature search through PubMed and identified 36 eligible studies. The overall analyses, subgroup analyses, as well as sensitivity analyses, were conducted to illustrate the association between diabetes mellitus and arthritis. Study quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale. All statistical analyses were conducted using STATA SE version 13.0. In our study, 36 eligible studies were identified and involved in the meta-analysis. The overall association between diabetes mellitus and arthritis is 1.61 (95% confidence interval [CI]: 1.14-2.28, P = .007). The association exists only in nongouty arthritis, where we observed the estimated odds ratio (OR) 1.33 (95% CI: 1.05-1.67, P < .001). The opposite point estimates from different types of diabetes may indicate possible different associations for type I (OR: 0.98, 95% CI: 0.18-5.39, P = .985) or type II diabetes (OR: 1.28, 95% CI: 0.88-1.84, P = .194). Diabetes mellitus performs more likely as a comorbidity of arthritis rather than a risk factor; however, more studies will be helpful to increase the confidence of identifying the association between diabetes and arthritis.

Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

PubMed Central

Tzoulaki, Ioanna; Zgaga, Lina; Ioannidis, John P A

2014-01-01

Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Data sources Medline, Embase, and screening of citations and references. Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable. PMID:24690624

Circulating linoleic acid and alpha-linolenic acid and glucose metabolism: the Hoorn Study.

PubMed

Cabout, Mieke; Alssema, Marjan; Nijpels, Giel; Stehouwer, Coen D A; Zock, Peter L; Brouwer, Ingeborg A; Elshorbagy, Amany K; Refsum, Helga; Dekker, Jacqueline M

2017-09-01

Data on the relation between linoleic acid (LA) and alpha-linolenic acid (ALA) and type 2 diabetes mellitus (T2DM) risk are scarce and inconsistent. The aim of this study was to investigate the association of serum LA and ALA with fasting and 2 h post-load plasma glucose and glycated hemoglobin (HbA1c). This study included 667 participants from third examination (2000) of the population-based Hoorn study in which individuals with glucose intolerance were overrepresented. Fatty acid profiles in serum total lipids were measured at baseline, in 2000. Diabetes risk markers were measured at baseline and follow-up in 2008. Linear regression models were used in cross-sectional and prospective analyses. In cross-sectional analyses (n = 667), serum LA was inversely associated with plasma glucose, both in fasting conditions (B = -0.024 [-0.045, -0.002]) and 2 h after glucose tolerance test (B = -0.099 [-0.158, -0.039]), but not with HbA1c (B = 0.000 [-0.014, 0.013]), after adjustment for relevant factors. In prospective analyses (n = 257), serum LA was not associated with fasting (B = 0.003 [-0.019, 0.025]) or post-load glucose (B = -0.026 [-0.100, 0.049]). Furthermore, no significant associations were found between serum ALA and glucose metabolism in cross-sectional or prospective analyses. In this study, serum LA was inversely associated with fasting and post-load glucose in cross-sectional, but not in prospective analyses. Further studies are needed to elucidate the exact role of serum LA and ALA levels and dietary polyunsaturated fatty acids in glucose metabolism.

Big Five personality characteristics are associated with depression subtypes and symptom dimensions of depression in older adults.

PubMed

Koorevaar, A M L; Hegeman, J M; Lamers, F; Dhondt, A D F; van der Mast, R C; Stek, M L; Comijs, H C

2017-12-01

This study examined the associations of personality characteristics with both subtypes and symptom dimensions of depression in older adults. Three hundred and seventy-eight depressed older adults participated in the Netherlands Study of Depression in Older Persons. Personality characteristics were assessed by the NEO-Five Factor Inventory. Subtypes and symptom dimensions of depression were determined using the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology (IDS). Multinomial logistic regression analyses were performed to examine the associations between personality and atypical, melancholic, and unspecified subtypes of major depression. Linear regression analyses examined the associations between personality and the IDS mood, somatic, and motivation symptom dimensions. The analyses were adjusted for confounders and additionally adjusted for depression severity. Neuroticism, Extraversion, Conscientiousness, and Agreeableness were associated with specified (atypical or melancholic) major depression compared with unspecified major depression in the bivariate analyses but lost their significance after adjustments for functional limitations and severity of depression. Neuroticism was positively associated with the IDS mood and motivation symptom dimensions, also in the adjusted models. Further, Extraversion and Agreeableness were negatively associated with the IDS mood symptom dimension, and Extraversion and Conscientiousness were negatively associated with the IDS motivation symptom dimension. None was associated with the IDS somatic symptom dimension. This study demonstrated the association of personality characteristics with mood and motivational symptoms of late-life depression. The lacking ability of personality to differentiate between melancholic and atypical depression seems to be largely explained by severity of depressive symptoms. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis.

PubMed

Eze, Ikenna C; Hemkens, Lars G; Bucher, Heiner C; Hoffmann, Barbara; Schindler, Christian; Künzli, Nino; Schikowski, Tamara; Probst-Hensch, Nicole M

2015-05-01

Air pollution is hypothesized to be a risk factor for diabetes. Epidemiological evidence is inconsistent and has not been systematically evaluated. We systematically reviewed epidemiological evidence on the association between air pollution and diabetes, and synthesized results of studies on type 2 diabetes mellitus (T2DM). We systematically searched electronic literature databases (last search, 29 April 2014) for studies reporting the association between air pollution (particle concentration or traffic exposure) and diabetes (type 1, type 2, or gestational). We systematically evaluated risk of bias and role of potential confounders in all studies. We synthesized reported associations with T2DM in meta-analyses using random-effects models and conducted various sensitivity analyses. We included 13 studies (8 on T2DM, 2 on type 1, 3 on gestational diabetes), all conducted in Europe or North America. Five studies were longitudinal, 5 cross-sectional, 2 case-control, and 1 ecologic. Risk of bias, air pollution assessment, and confounder control varied across studies. Dose-response effects were not reported. Meta-analyses of 3 studies on PM2.5 (particulate matter ≤ 2.5 μm in diameter) and 4 studies on NO2 (nitrogen dioxide) showed increased risk of T2DM by 8-10% per 10-μg/m3 increase in exposure [PM2.5: 1.10 (95% CI: 1.02, 1.18); NO2: 1.08 (95% CI: 1.00, 1.17)]. Associations were stronger in females. Sensitivity analyses showed similar results. Existing evidence indicates a positive association of air pollution and T2DM risk, albeit there is high risk of bias. High-quality studies assessing dose-response effects are needed. Research should be expanded to developing countries where outdoor and indoor air pollution are high.

Testosterone replacement therapy and the heart: friend, foe or bystander?

PubMed Central

Canfield, Steven; Wang, Run

2016-01-01

The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, “beneficial (friendly use)”, “detrimental (foe)” and “no effects at all (bystander)”, based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT’s). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT’s does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not. PMID:28078222

Testosterone replacement therapy and the heart: friend, foe or bystander?

PubMed

Lopez, David S; Canfield, Steven; Wang, Run

2016-12-01

The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, "beneficial (friendly use)", "detrimental (foe)" and "no effects at all (bystander)", based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT's). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT's does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

PubMed

Gu, F; Pfeiffer, R M; Bhattacharjee, S; Han, S S; Taylor, P R; Berndt, S; Yang, H; Sigurdson, A J; Toro, J; Mirabello, L; Greene, M H; Freedman, N D; Abnet, C C; Dawsey, S M; Hu, N; Qiao, Y-L; Ding, T; Brenner, A V; Garcia-Closas, M; Hayes, R; Brinton, L A; Lissowska, J; Wentzensen, N; Kratz, C; Moore, L E; Ziegler, R G; Chow, W-H; Savage, S A; Burdette, L; Yeager, M; Chanock, S J; Chatterjee, N; Tucker, M A; Goldstein, A M; Yang, X R

2013-04-02

The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses.

PubMed

Matthews, Abigail G; Hoffman, Eric K; Zezza, Nicholas; Stiffler, Scott; Hill, Shirley Y

2007-09-01

The genes encoding the gamma-aminobutyric acid(A) (GABA(A)) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/unaffected sib pairs (all p's < .13). There was no evidence of a within-family association (all p's > .39). Comorbidity may explain why our results differ from those in the literature. The presence of primary drug dependence and/or other psychiatric disorders is minimal in our pedigrees, although several of the other previously published multiplex family analyses exhibit a greater degree of comorbidity.

Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study

PubMed Central

Bossini-Castillo, Lara; Martin, Jose Ezequiel; Broen, Jasper; Simeon, Carmen P; Beretta, Lorenzo; Gorlova, Olga Y; Vonk, Madelon C; Ortego-Centeno, Norberto; Espinosa, Gerard; Carreira, Patricia; García de la Peña, Paloma; Oreiro, Natividad; Román-Ivorra, José Andrés; Castillo, María Jesús; González-Gay, Miguel A; Sáez-Comet, Luis; Castellví, Ivan; Schuerwegh, Annemie J; Voskuyl, Alexandre E; Hoffmann-Vold, Anna-Maria; Hesselstrand, Roger; Nordin, Annika; Lunardi, Claudio; Scorza, Raffaella; van Laar, Jacob M; Shiels, Paul G; Herrick, Ariane; Worthington, Jane; Fonseca, Carmen; Denton, Christopher; Tan, Filemon K; Arnett, Frank C; Assassi, Shervin; Koeleman, Bobby P; Mayes, Maureen D; Radstake, Timothy R D J; Martin, Javier

2013-01-01

Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. Results Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 pMH=1.94×10−4, OR 1.19; rs4958881 pMH=3.26×10−5, OR 1.19; rs3792783 pMH=2.16×10−4, OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. Conclusions These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor. PMID:22896740

Comprehensive replication of the relationship between myopia-related genes and refractive errors in a large Japanese cohort.

PubMed

Yoshikawa, Munemitsu; Yamashiro, Kenji; Miyake, Masahiro; Oishi, Maho; Akagi-Kurashige, Yumiko; Kumagai, Kyoko; Nakata, Isao; Nakanishi, Hideo; Oishi, Akio; Gotoh, Norimoto; Yamada, Ryo; Matsuda, Fumihiko; Yoshimura, Nagahisa

2014-10-21

We investigated the association between refractive error in a Japanese population and myopia-related genes identified in two recent large-scale genome-wide association studies. Single-nucleotide polymorphisms (SNPs) in 51 genes that were reported by the Consortium for Refractive Error and Myopia and/or the 23andMe database were genotyped in 3712 healthy Japanese volunteers from the Nagahama Study using HumanHap610K Quad, HumanOmni2.5M, and/or HumanExome Arrays. To evaluate the association between refractive error and recently identified myopia-related genes, we used three approaches to perform quantitative trait locus analyses of mean refractive error in both eyes of the participants: per-SNP, gene-based top-SNP, and gene-based all-SNP analyses. Association plots of successfully replicated genes also were investigated. In our per-SNP analysis, eight myopia gene associations were replicated successfully: GJD2, RASGRF1, BICC1, KCNQ5, CD55, CYP26A1, LRRC4C, and B4GALNT2.Seven additional gene associations were replicated in our gene-based analyses: GRIA4, BMP2, QKI, BMP4, SFRP1, SH3GL2, and EHBP1L1. The signal strength of the reported SNPs and their tagging SNPs increased after considering different linkage disequilibrium patterns across ethnicities. Although two previous studies suggested strong associations between PRSS56, LAMA2, TOX, and RDH5 and myopia, we could not replicate these results. Our results confirmed the significance of the myopia-related genes reported previously and suggested that gene-based replication analyses are more effective than per-SNP analyses. Our comparison with two previous studies suggested that BMP3 SNPs cause myopia primarily in Caucasian populations, while they may exhibit protective effects in Asian populations. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Caffeine, cognitive failures and health in a non-working community sample.

PubMed

Smith, Andrew P

2009-01-01

Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Secondary analyses of a large epidemiological database (N = 3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17-92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140 mg/day, range 0-1800 mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression.

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

PubMed

Ekoru, Kenneth; Young, Elizabeth H; Dillon, David G; Gurdasani, Deepti; Stehouwer, Nathan; Faurholt-Jepsen, Daniel; Levitt, Naomi S; Crowther, Nigel J; Nyirenda, Moffat; Njelekela, Marina A; Ramaiya, Kaushik; Nyan, Ousman; Adewole, Olanisun O; Anastos, Kathryn; Compostella, Caterina; Dave, Joel A; Fourie, Carla M; Friis, Henrik; Kruger, Iolanthe M; Longenecker, Chris T; Maher, Dermot P; Mutimura, Eugene; Ndhlovu, Chiratidzo E; Praygod, George; Pefura Yone, Eric W; Pujades-Rodriguez, Mar; Range, Nyagosya; Sani, Mahmoud U; Sanusi, Muhammad; Schutte, Aletta E; Sliwa, Karen; Tien, Phyllis C; Vorster, Este H; Walsh, Corinna; Gareta, Dickman; Mashili, Fredirick; Sobngwi, Eugene; Adebamowo, Clement; Kamali, Anatoli; Seeley, Janet; Smeeth, Liam; Pillay, Deenan; Motala, Ayesha A; Kaleebu, Pontiano; Sandhu, Manjinder S

2018-01-01

Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I 2 =45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Alcohol intake and gastric cancer: Meta-analyses of published data versus individual participant data pooled analyses (StoP Project).

PubMed

Ferro, Ana; Morais, Samantha; Rota, Matteo; Pelucchi, Claudio; Bertuccio, Paola; Bonzi, Rossella; Galeone, Carlotta; Zhang, Zuo-Feng; Matsuo, Keitaro; Ito, Hidemi; Hu, Jinfu; Johnson, Kenneth C; Yu, Guo-Pei; Palli, Domenico; Ferraroni, Monica; Muscat, Joshua; Malekzadeh, Reza; Ye, Weimin; Song, Huan; Zaridze, David; Maximovitch, Dmitry; Fernández de Larrea, Nerea; Kogevinas, Manolis; Vioque, Jesus; Navarrete-Muñoz, Eva M; Pakseresht, Mohammadreza; Pourfarzi, Farhad; Wolk, Alicja; Orsini, Nicola; Bellavia, Andrea; Håkansson, Niclas; Mu, Lina; Pastorino, Roberta; Kurtz, Robert C; Derakhshan, Mohammad H; Lagiou, Areti; Lagiou, Pagona; Boffetta, Paolo; Boccia, Stefania; Negri, Eva; La Vecchia, Carlo; Peleteiro, Bárbara; Lunet, Nuno

2018-05-01

Individual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer. We compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies. A total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07-1.36) vs. 1.10 (0.99-1.23)] and more heterogeneous (I 2 : 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias. Meta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Residential exposure to traffic noise and leisure-time sports - A population-based study.

PubMed

Roswall, Nina; Ammitzbøll, Gunn; Christensen, Jeppe Schultz; Raaschou-Nielsen, Ole; Jensen, Steen Solvang; Tjønneland, Anne; Sørensen, Mette

2017-08-01

Traffic levels have been found a significant environmental predictor for physical inactivity. A recent study suggested that traffic noise annoyance was associated with lower physical activity. We investigated associations between modelled residential traffic noise and leisure-time sports. In the Diet, Cancer and Health cohort, we performed cross-sectional analyses using data from the baseline questionnaire (1993-97), and longitudinal analyses of change between baseline and follow-up (2000-02). People reported participation (yes/no) and hours of leisure-time sport, from which we calculated MET hrs/week. Present and historical addresses from 1987 to 2002 were found in national registries, and traffic noise was modelled 1 and 5 years before enrolment, and from baseline to follow-up. Analyses were performed using logistic and linear regression. Traffic noise exposure 5 years before baseline was associated with higher prevalence odds ratio of non-participation in leisure-time sports; significantly for road traffic noise (odds ratio (OR): 1.10; 95% confidence interval (CI): 1.07-1.13) and borderline for railway noise (OR: 1.03; 95% CI: 0.99-1.07), per 10dB. In longitudinal analyses, a 10dB higher road traffic noise was associated with a higher prevalence odds ratio of ceasing (OR: 1.12; 95% CI: 1.07-1.18) and a lower prevalence odds ratio of initiating (OR: 0.92; 95% CI: 0.87-0.96) leisure-time sports. Exposure to railway noise was negatively associated with baseline MET hrs/week, whereas no association was found in longitudinal analyses, or for road traffic noise. The study suggests that long-term exposure to residential road traffic noise is negatively associated with leisure-time sports. Results for railway noise were less consistent. Copyright © 2017 Elsevier GmbH. All rights reserved.

Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review.

PubMed

Harris, Holly R; Terry, Kathryn L

2016-01-01

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with an estimated prevalence of 4-21% in reproductive aged women. The altered metabolic and hormonal environment among women with PCOS may increase their risk of some types of cancer. We performed a comprehensive review of the literature using numerous search terms for all studies examining the associations between polycystic ovary syndrome and related characteristics and cancer published in English through October 2016. This review summarizes the epidemiological findings on the associations between PCOS and endometrial, ovarian, and breast cancers and discusses the methodological issues, complexities, and underlying mechanisms of these associations. We identified 11 individual studies and 3 meta-analyses on the associations between PCOS and endometrial cancer, 8 studies and 1 meta-analysis for ovarian cancer, and 10 studies and 1 meta-analysis for breast cancer. Multiple studies reported that women with PCOS were at a higher risk for endometrial cancer; however, many did not take into account body mass index (BMI), a strong and well-established risk factor for endometrial cancer. The association with ovarian cancer was less clear, but a potentially increased risk of the borderline serous subtype was reported by two studies. No consistent association between PCOS risk and breast cancer was observed. The associations between PCOS and endometrial, ovarian, and breast cancer are complex, with the need to consider many methodological issues in future analyses. Larger well-designed studies, or pooled analyses, may help clarify these complex associations.

Meta-analyses of HFE variants in coronary heart disease.

PubMed

Lian, Jiangfang; Xu, Limin; Huang, Yi; Le, Yanping; Jiang, Danjie; Yang, Xi; Xu, Weifeng; Huang, Xiaoyan; Dong, Changzheng; Ye, Meng; Zhou, Jianqing; Duan, Shiwei

2013-09-15

HFE gene variants can cause hereditary hemochromatosis (HH) that often comes along with an increased risk of coronary heart disease (CHD). The goal of our study is to assess the contribution of four HFE gene variants to the risk of CHD. We conducted four meta-analyses of the studies examining the association between four HFE gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. Meta-analyses showed that HFE rs1799945-G allele was associated with a 6% increased risk of CHD (P=0.02, odds ratio (OR)=1.06, 95% confidence interval (CI)=1.01-1.11). However, no association between the other three HFE gene variants (rs1800562, rs1800730, and rs9366637) and CHD risk was observed by the meta-analyses (all P values>0.05). In addition, the results of our case-control study indicated that rs1800562 and rs1800730 were monomorphic, and that rs1799945 and rs9366637 were not associated with CHD in Han Chinese. Our meta-analysis suggested that a significant association existed between rs1799945 mutation and CHD, although this mutation was rare in Han Chinese. Copyright © 2013 Elsevier B.V. All rights reserved.

Biomass fuel use for household cooking in Swaziland: is there an association with anaemia and stunting in children aged 6-36 months?

PubMed

Machisa, Mercilene; Wichmann, Janine; Nyasulu, Peter S

2013-09-01

This study is the second to investigate the association between the use of biomass fuels (BMF) for household cooking and anaemia and stunting in children. Such fuels include coal, charcoal, wood, dung and crop residues. Data from the 2006-2007 Swaziland Demographic and Health Survey (a cross-sectional study design) were analysed. Childhood stunting was ascertained through age and height, and anaemia through haemoglobin measurement. The association between BMF use and health outcomes was determined in multinomial logistic regression analyses. Various confounders were considered in the analyses. A total of 1150 children aged 6-36 months were included in the statistical analyses, of these 596 (51.8%) and 317 (27.6%) were anaemic and stunted, respectively. BMF use was not significantly associated with childhood anaemia in univariate analysis. Independent risk factors for childhood anaemia were child's age, history of childhood diarrhoea and mother's anaemia status. No statistically significant association was observed between BMF use and childhood stunting, after adjusting for child's gender, age, birth weight and preceding birth interval. This study identified the need to prioritize childhood anaemia and stunting as health outcomes and the introduction of public health interventions in Swaziland. Further research is needed globally on the potential effects of BMF use on childhood anaemia and stunting.

The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses

PubMed Central

Ren, Meng; Li, Na; Wang, Zhan; Liu, Yisi; Chen, Xi; Chu, Yuanyuan; Li, Xiangyu; Zhu, Zhongmin; Tian, Liqiao; Xiang, Hao

2017-01-01

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified–case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m3 increment in SO2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case–crossover analysis displayed greater variation than that from the time-series analysis. PMID:28084399

The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses.

PubMed

Ren, Meng; Li, Na; Wang, Zhan; Liu, Yisi; Chen, Xi; Chu, Yuanyuan; Li, Xiangyu; Zhu, Zhongmin; Tian, Liqiao; Xiang, Hao

2017-01-13

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m 3 increment in SO 2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO 2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.

The short-term effects of air pollutants on respiratory disease mortality in Wuhan, China: comparison of time-series and case-crossover analyses

NASA Astrophysics Data System (ADS)

Ren, Meng; Li, Na; Wang, Zhan; Liu, Yisi; Chen, Xi; Chu, Yuanyuan; Li, Xiangyu; Zhu, Zhongmin; Tian, Liqiao; Xiang, Hao

2017-01-01

Few studies have compared different methods when exploring the short-term effects of air pollutants on respiratory disease mortality in Wuhan, China. This study assesses the association between air pollutants and respiratory disease mortality with both time-series and time-stratified-case-crossover designs. The generalized additive model (GAM) and the conditional logistic regression model were used to assess the short-term effects of air pollutants on respiratory disease mortality. Stratified analyses were performed by age, sex, and diseases. A 10 μg/m3 increment in SO2 level was associated with an increase in relative risk for all respiratory disease mortality of 2.4% and 1.9% in the case-crossover and time-series analyses in single pollutant models, respectively. Strong evidence of an association between NO2 and daily respiratory disease mortality among men or people older than 65 years was found in the case-crossover study. There was a positive association between air pollutants and respiratory disease mortality in Wuhan, China. Both time-series and case-crossover analyses consistently reveal the association between three air pollutants and respiratory disease mortality. The estimates of association between air pollution and respiratory disease mortality from the case-crossover analysis displayed greater variation than that from the time-series analysis.

Chemical Warfare Study: Summary Report

DTIC Science & Technology

1985-02-01

Performed under subcontract for INSTITUTE FOR DEFENSE ANALYSES Burdeshaw Associates, Ltd. 4701 Sangamore Road Bethesda, Maryland 20816 February 1985...Associates, Ltd. 4701 Sangamore Road Bethesda, Maryland 20816 11. CONTROLUNG OFFICE NAME AND ADDRESS Office of the 0nder Secretary of Defense for...Associates, Ltd. 4701 Sangamore Road Bethesda, Maryland 20816 February 1985 IDA INSTITUTE FOR DEFENSE ANALYSES Contract MDA 903 84 C 0031 Task T-3-200 o

Quality control and conduct of genome-wide association meta-analyses.

PubMed

Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth J F

2014-05-01

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

Quality control and conduct of genome-wide association meta-analyses

PubMed Central

Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Mägi, Reedik; Ferreira, Teresa; Fall, Tove; Graff, Mariaelisa; Justice, Anne E; Luan, Jian'an; Gustafsson, Stefan; Randall, Joshua C; Vedantam, Sailaja; Workalemahu, Tsegaselassie; Kilpeläinen, Tuomas O; Scherag, André; Esko, Tonu; Kutalik, Zoltán; Heid, Iris M; Loos, Ruth JF

2014-01-01

Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for [1] organizational aspects of GWAMAs, and for [2] QC at the study file level, the meta-level across studies, and the meta-analysis output level. Real–world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for use of a powerful and flexible software package called EasyQC. For consortia of comparable size to the GIANT consortium, the present protocol takes a minimum of about 10 months to complete. PMID:24762786

Systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men.

PubMed

Cartwright, Rufus; Mangera, Altaf; Tikkinen, Kari A O; Rajan, Prabhakar; Pesonen, Jori; Kirby, Anna C; Thiagamoorthy, Ganesh; Ambrose, Chris; Gonzalez-Maffe, Juan; Bennett, Phillip R; Palmer, Tom; Walley, Andrew; Järvelin, Marjo-Riitta; Khullar, Vik; Chapple, Chris

2014-10-01

Although family studies have shown that male lower urinary tract symptoms (LUTS) are highly heritable, no systematic review exists of genetic polymorphisms tested for association with LUTS. To systematically review and meta-analyze studies assessing candidate polymorphisms/genes tested for an association with LUTS, and to assess the strength, consistency, and potential for bias among pooled associations. A systematic search of the PubMed and HuGE databases as well as abstracts of major urologic meetings was performed through to January 2013. Case-control studies reporting genetic associations in men with LUTS were included. Reviewers independently and in duplicate screened titles, abstracts, and full texts to determine eligibility, abstracted data, and assessed the credibility of pooled associations according to the interim Venice criteria. Authors were contacted for clarifications if needed. Meta-analyses were performed for variants assessed in more than two studies. We identified 74 eligible studies containing data on 70 different genes. A total of 35 meta-analyses were performed with statistical significance in five (ACE, ELAC2, GSTM1, TERT, and VDR). The heterogeneity was high in three of these meta-analyses. The rs731236 variant of the vitamin D receptor had a protective effect for LUTS (odds ratio: 0.64; 95% confidence interval, 0.49-0.83) with moderate heterogeneity (I(2)=27.2%). No evidence for publication bias was identified. Limitations include wide-ranging phenotype definitions for LUTS and limited power in most meta-analyses to detect smaller effect sizes. Few putative genetic risk variants have been reliably replicated across populations. We found consistent evidence of a reduced risk of LUTS associated with the common rs731236 variant of the vitamin D receptor gene in our meta-analyses. Combining the results from all previous studies of genetic variants that may cause urinary symptoms in men, we found significant variants in five genes. Only one, a variant of the vitamin D receptor, was consistently protective across different populations. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

permGPU: Using graphics processing units in RNA microarray association studies.

PubMed

Shterev, Ivo D; Jung, Sin-Ho; George, Stephen L; Owzar, Kouros

2010-06-16

Many analyses of microarray association studies involve permutation, bootstrap resampling and cross-validation, that are ideally formulated as embarrassingly parallel computing problems. Given that these analyses are computationally intensive, scalable approaches that can take advantage of multi-core processor systems need to be developed. We have developed a CUDA based implementation, permGPU, that employs graphics processing units in microarray association studies. We illustrate the performance and applicability of permGPU within the context of permutation resampling for a number of test statistics. An extensive simulation study demonstrates a dramatic increase in performance when using permGPU on an NVIDIA GTX 280 card compared to an optimized C/C++ solution running on a conventional Linux server. permGPU is available as an open-source stand-alone application and as an extension package for the R statistical environment. It provides a dramatic increase in performance for permutation resampling analysis in the context of microarray association studies. The current version offers six test statistics for carrying out permutation resampling analyses for binary, quantitative and censored time-to-event traits.

LOD score exclusion analyses for candidate genes using random population samples.

PubMed

Deng, H W; Li, J; Recker, R R

2001-05-01

While extensive analyses have been conducted to test for, no formal analyses have been conducted to test against, the importance of candidate genes with random population samples. We develop a LOD score approach for exclusion analyses of candidate genes with random population samples. Under this approach, specific genetic effects and inheritance models at candidate genes can be analysed and if a LOD score is < or = - 2.0, the locus can be excluded from having an effect larger than that specified. Computer simulations show that, with sample sizes often employed in association studies, this approach has high power to exclude a gene from having moderate genetic effects. In contrast to regular association analyses, population admixture will not affect the robustness of our analyses; in fact, it renders our analyses more conservative and thus any significant exclusion result is robust. Our exclusion analysis complements association analysis for candidate genes in random population samples and is parallel to the exclusion mapping analyses that may be conducted in linkage analyses with pedigrees or relative pairs. The usefulness of the approach is demonstrated by an application to test the importance of vitamin D receptor and estrogen receptor genes underlying the differential risk to osteoporotic fractures.

Associations between residential traffic noise exposure and smoking habits and alcohol consumption-A population-based study.

PubMed

Roswall, Nina; Christensen, Jeppe Schultz; Bidstrup, Pernille Envold; Raaschou-Nielsen, Ole; Jensen, Steen Solvang; Tjønneland, Anne; Sørensen, Mette

2018-05-01

Traffic noise stresses and disturbs sleep. It has been associated with various diseases, and has recently also been associated with lifestyle. Hence, the association between traffic noise and disease could partly operate via a pathway of lifestyle habits, including smoking and alcohol intake. We investigated associations between modelled residential traffic noise and smoking habits and alcohol consumption. In a cohort of 57,053 participants, we performed cross-sectional analyses using data from a baseline questionnaire (1993-97), and longitudinal analyses of change between baseline and follow-up (2000-02). Smoking status (never, former, current) and intensity (tobacco, g/day) and alcohol consumption (g/day) was self-reported at baseline and follow-up. Address history from 1987-2002 for all participants were found in national registries, and road traffic and railway noise was modelled 1 and 5 years before enrolment, and from baseline to follow-up. Analyses were performed using logistic and linear regression, and adjusted for demographics, socioeconomic variables, leisure-time sports, and noise from the opposite source (road/railway). Road traffic noise exposure 5 years before baseline was positively associated with alcohol consumption (adjusted difference per 10 dB: 1.38 g/day, 95% confidence interval (CI): 1.10-1.65), smoking intensity (adjusted difference per 10 dB: 0.40 g/day, 95% CI: 0.19-0.61), and odds for being a current vs. never/former smoker at baseline (odds ratio (OR): 1.14; 95% CI: 1.10-1.17). In longitudinal analyses, we found no association between road traffic noise and change in smoking and alcohol habits. Railway noise was not associated with smoking habits and alcohol consumption, neither in cross-sectional nor in longitudinal analyses. The study suggests that long-term exposure to residential road traffic is associated with smoking habits and alcohol consumption, albeit only in cross-sectional, but not in longitudinal analyses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Type D personality and health status in cardiovascular disease populations: a meta-analysis of prospective studies.

PubMed

Versteeg, Henneke; Spek, Viola; Pedersen, Susanne S; Denollet, Johan

2012-12-01

Knowledge of the factors associated with individual differences in patient-reported outcomes is essential to identify high-risk patients and improve secondary prevention. In this meta-analysis, we examined the association between Type D personality and the individual differences in patient-reported physical and mental health status among cardiovascular patients. A computerized search of the literature through PUBMED and PsychINFO (from 1995 to May 2011) was performed and prospective studies were selected that analysed the association between Type D personality and health status in cardiovascular patients. Two separate meta-analyses were performed for the association of Type D personality with physical and mental health status, respectively. Of all identified studies, ten studies met the selection criteria. The meta-analyses showed that Type D was associated with a two-fold increased odds for impaired physical health status (3035 patients, OR 1.94, 95% CI 1.49-2.52) and a 2.5-fold increased odds for impaired mental health status (2213 patients, OR 2.55, 95% CI 1.57-4.16). There was no significant heterogeneity between the studies on physical health status (Q = 12.78; p = 0.17; I(2 )= 29.59), but there was between those on mental health status (Q = 21.91; p = 0.003; I(2 )= 68.04). Subgroup analyses showed that the association between Type D and mental health status decreased yet remained significant when adjusting for baseline health status. Type D personality was shown to be an independent correlate of impaired patient-reported physical and mental health status in various cardiovascular patient groups. Clinicians should be aware of the association between chronic psychological distress and poor patient-reported outcomes.

Association study of 21 circadian genes with bipolar I disorder, schizoaffective disorder, and schizophrenia

PubMed Central

Mansour, Hader A; Talkowski, Michael E; Wood, Joel; Chowdari, Kodavali V; McClain, Lora; Prasad, Konasale; Montrose, Debra; Fagiolini, Andrea; Friedman, Edward S; Allen, Michael H; Bowden, Charles L; Calabrese, Joseph; El-Mallakh, Rif S; Escamilla, Michael; Faraone, Stephen V; Fossey, Mark D; Gyulai, Laszlo; Loftis, Jennifer M; Hauser, Peter; Ketter, Terence A; Marangell, Lauren B; Miklowitz, David J; Nierenberg, Andrew A; Patel, Jayendra; Sachs, Gary S; Sklar, Pamela; Smoller, Jordan W; Laird, Nan; Keshavan, Matcheri; Thase, Michael E; Axelson, David; Birmaher, Boris; Lewis, David; Monk, Tim; Frank, Ellen; Kupfer, David J; Devlin, Bernie; Nimgaonkar, Vishwajit L

2012-01-01

Objective Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders. Methods We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS). Results Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL. Conclusions Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results. PMID:19839995

Beyond the usual suspects: a multidimensional genetic exploration of infant attachment disorganization and security.

PubMed

Pappa, Irene; Szekely, Eszter; Mileva-Seitz, Viara R; Luijk, Maartje P C M; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-01-01

Although the environmental influences on infant attachment disorganization and security are well-studied, little is known about their heritability. Candidate gene studies have shown small, often non-replicable effects. In this study, we gathered the largest sample (N = 657) of ethnically homogenous, 14-month-old children with both observed attachment and genome-wide data. First, we used a Genome-Wide Association Study (GWAS) approach to identify single nucleotide polymorphisms (SNPs) associated with attachment disorganization and security. Second, we annotated them into genes (Versatile Gene-based Association Study) and functional pathways. Our analyses provide evidence of novel genes (HDAC1, ZNF675, BSCD1) and pathways (synaptic transmission, cation transport) associated with attachment disorganization. Similar analyses identified a novel gene (BECN1) but no distinct pathways associated with attachment security. The results of this first extensive, exploratory study on the molecular-genetic basis of infant attachment await replication in large, independent samples.

SNPassoc: an R package to perform whole genome association studies.

PubMed

González, Juan R; Armengol, Lluís; Solé, Xavier; Guinó, Elisabet; Mercader, Josep M; Estivill, Xavier; Moreno, Víctor

2007-03-01

The popularization of large-scale genotyping projects has led to the widespread adoption of genetic association studies as the tool of choice in the search for single nucleotide polymorphisms (SNPs) underlying susceptibility to complex diseases. Although the analysis of individual SNPs is a relatively trivial task, when the number is large and multiple genetic models need to be explored it becomes necessary a tool to automate the analyses. In order to address this issue, we developed SNPassoc, an R package to carry out most common analyses in whole genome association studies. These analyses include descriptive statistics and exploratory analysis of missing values, calculation of Hardy-Weinberg equilibrium, analysis of association based on generalized linear models (either for quantitative or binary traits), and analysis of multiple SNPs (haplotype and epistasis analysis). Package SNPassoc is available at CRAN from http://cran.r-project.org. A tutorial is available on Bioinformatics online and in http://davinci.crg.es/estivill_lab/snpassoc.

[The association between socioeconomic indicators andadolescents'physical activity and health-related fitness].

PubMed

Constantino-Coledam, Diogo H; Ferraiol, Philippe Fanelli; Arruda, Gustavo Aires de; Pires-Júnior, Raymundo; Teixeira, Marcio; Greca, João Paulo de Aguiar; Oliveira, Arli Ramos de

2013-01-01

This study was aimed at analysing the association between socioeconomic indicators and adolescents' physical activity and health-related fitness. The study involved 716 adolescents from both genders whose age ranged from 10 to 18 years-old (46.8% male) who answered a questionnaire for estimating their habitual physical activity, socioeconomic status; two health-related physical fitness tests were also performed. The socioeconomic indicators analysed concerned their parents' educational level and the number of bathrooms, TVs, cars, housemaids, refrigerators and freezers in their homes. A positive association was found between paternal education (PR=1.61 (range 1.27-2.10) and 1.41 (1.10-1.83)) and housemaids (PR=1.97 (1.04-3.81) and 1.92 (1.05-3.52)) with recommended physical activity and leisure time physical activity, respectively. The number of cars (PR=1.48: 1.02-2.19) and freezers (PR=1.88: 1.12-3.18) was positively associated with leisure time physical activity and the number of TVs negatively so (PR=0.75: 0.63-0.89). The number of TVs (PR=0.80: 0.67-0.96) and cars (PR=0.70: 0.55-0.89) was negatively associated with cardiorespiratory fitness whilst paternal education (PR=1.17: 1.00-1.37) and the number of bathrooms in the home (PR=1.25: 1.02-1.54) were positively associated with muscular strength. Physical activity and health-related physical fitness were associated with socioeconomic status. However, such association depended on the socioeconomic indicator being analysed. Caution should be taken when analysing studies which use different socioeconomic indicators.

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

PubMed Central

Liang, Jingjing; Le, Thu H.; Edwards, Digna R. Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Schwander, Karen; McKenzie, Colin A.; Fox, Ervin; Nalls, Michael A.; Young, J. Hunter; Lane, Jacqueline M.; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K.; Wang, Heming; Forrester, Terrence; Chu, Pei-Lun; Evans, Michele K.; Morrison, Alanna C.; Martin, Lisa W.; Wiggins, Kerri L.; Hui, Qin; Zhao, Wei; Jackson, Rebecca D.; Faul, Jessica D.; Reiner, Alex P.; Bray, Michael; Denny, Joshua C.; Mosley, Thomas H.; Palmas, Walter; Guo, Xiuqing; Polak, Joseph F.; Taylor, Ken D.; Boerwinkle, Eric; Bottinger, Erwin P.; Liu, Kiang; Risch, Neil; Hunt, Steven C.; Kooperberg, Charles; Zonderman, Alan B.; Becker, Diane M.; Cai, Jianwen; Loos, Ruth J. F.; Psaty, Bruce M.; Weir, David R.; Kardia, Sharon L. R.; Arnett, Donna K.; Won, Sungho; Edwards, Todd L.; Redline, Susan; Cooper, Richard S.; Rao, D. C.; Rotimi, Charles; Levy, Daniel; Chakravarti, Aravinda

2017-01-01

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension. PMID:28498854

Caffeine at work.

PubMed

Smith, Andrew P

2005-08-01

There is a large literature on the effects of caffeine on performance. Most of the studies have been conducted in the laboratory and further information is required on the effects of caffeine consumption on performance and safety at work. The present studies aimed to determine whether the level of caffeine consumption influenced changes in alertness and performance over the working day. Secondary analyses of a large epidemiological database were also conducted to examine associations between caffeine consumption and cognitive failures and accidents at work. In the first study 110 volunteers, all of whom were regular caffeine consumers, rated their alertness and carried out a simple reaction time task before and after work on a Monday and Friday. Caffeine consumption during the day was recorded and volunteers were sub-divided into low and high consumers on the basis of a median split (220 mg/day). The second study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. In the first analyses associations between caffeine consumption and frequency of cognitive failures were examined in a sample of 1253 white-collar workers. The second set of analyses examined associations between caffeine consumption and accidents at work in a sample of 1555 workers who were especially at risk of having an accident. The results from the first study showed that those who consumed higher levels of caffeine reported significantly greater increases in alertness over the working day and a significantly smaller slowing of reaction time. The results from the second study demonstrated significant associations between caffeine consumption and fewer cognitive failures and accidents at work. After controlling for possible confounding factors it was found that higher caffeine consumption was associated with about half the risk of frequent/very frequent cognitive failures and a similar reduction in risk for accidents at work. Overall, the results from the three analyses show that caffeine consumption may have benefits for performance and safety at work. Copyright (c) 2005 John Wiley & Sons, Ltd.

Educational inequality in cardiovascular diseases: a sibling approach.

PubMed

Søndergaard, Grethe; Dalton, Susanne Oksbjerg; Mortensen, Laust Hvas; Osler, Merete

2018-02-01

Educational inequality in diseases in the circulatory system (here termed cardiovascular disease) is well documented but may be confounded by early life factors. The aim of this observational study was to examine whether the associations between education and all cardiovascular diseases, ischaemic heart disease and stroke, respectively, were explained by family factors shared by siblings. The study population included all individuals born in Denmark between 1950 and 1979 who had at least one full sibling born in the same period. Using Cox regression, data were analysed in conventional cohort and within-sibship analyses in which the association was examined within siblings discordant on education. Assuming that attenuation of associations in the within-sibship as compared with the cohort analyses would indicate confounding from factors shared within families. A lower educational status was associated with a higher risk of cardiovascular disease, ischaemic heart disease and stroke. All associations attenuated in the within-sibship analyses, in particular in the analyses on ischaemic heart disease before age 45 years. For instance, in the cohort analyses, the hazard rate of ischaemic heart disease among women less than 45 years who had a primary school education was 94% (hazard ratio 1.94 (1.78-2.12) higher than among those with a vocational education, while it attenuated to 51% (hazard ratio 1.51 (1.34-1.71)) in the within-sibship analysis. Confounding from factors shared by siblings explained the associations between education and the cardiovascular disease outcomes but to varying degrees. This should be taken into account when planning interventions aimed at reducing educational inequalities in the development of cardiovascular disease, ischaemic heart disease and stroke.

Semantic associative relations and conceptual processing.

PubMed

Di Giacomo, Dina; De Federicis, Lucia Serenella; Pistelli, Manuela; Fiorenzi, Daniela; Passafiume, Domenico

2012-02-01

We analysed the organisation of semantic network using associative mechanisms between different types of information and studied the progression of the use of these associative relations during development. We aimed to verify the linkage of concepts with the use of semantic associative relations. The goal of this study was to analyse the cognitive ability to use associative relations between various items when describing old and/or new concepts. We examined the performance of 100 subjects between the ages of 4 and 7 years on an experimental task using five associative relations based on verbal encoding. The results showed that children are able to use the five semantic associative relations at age 4, but performance with each of the different associative relations improves at different times during development. Functional and part/whole relations develop at an early age, whereas the superordinate relations develop later. Our study clarified the characteristics of the progression of semantic associations during development as well as the roles that associative relations play in the structure and improvement of the semantic store.

The Association of Albuminuria With Tubular Reabsorption of Uric Acid: Results From a General Population Cohort

PubMed Central

Scheven, Lieneke; Joosten, Michel M.; de Jong, Paul E.; Bakker, Stephan J. L.; Gansevoort, Ron T.

2014-01-01

Background Elevated albuminuria as well as an increased serum uric acid concentration is associated with poor cardiovascular outcome. We questioned whether these 2 variables (albuminuria and serum uric concentration) may be interrelated via tubular uric acid reabsorption. Methods and Results Included were 7688 participants of the PREVEND Study, an observational, general population‐based cohort study. Linear regression analyses were used to test associations of baseline albuminuria with baseline serum uric acid concentration and tubular uric acid reabsorption (calculated as [100−fractional uric acid excretion]%). Cox regression analyses were used to study the association of baseline serum uric acid and albuminuria with incident cardiovascular morbidity and mortality. In cross‐sectional analyses, albuminuria was associated positively with serum uric acid concentration, both crude and after adjustment for potential confounders (both P<0.001). Albuminuria was found to be associated positively with tubular uric acid reabsorption, again both crude and after adjustment for potential confounders (both P<0.001). In longitudinal analyses during a median follow‐up of 10.5 years, 702 cardiovascular events occurred. After adjusting for cardiovascular risk factors, both albuminuria and serum uric acid were associated with incident cardiovascular events (Hazard Ratios 1.09 [1.03 to 1.17], P=0.01 and 1.19 [1.09 to 1.30], P<0.001, respectively). A significant interaction between these variables was present (P<0.001), consistent with high serum uric acid being less predictive for cardiovascular morbidity and mortality in the presence of high albuminuria and vice versa. Conclusions Albuminuria is strongly associated with tubular uric acid reabsorption, and consequently with serum uric acid concentration. This phenomenon may explain in part why albuminuria is associated with cardiovascular outcome. PMID:24772520

Failed reciprocity in close social relationships and health: findings from the Whitehall II study.

PubMed

Chandola, Tarani; Marmot, Michael; Siegrist, Johannes

2007-10-01

To extend the model of effort-reward imbalance at work to close and more general social relationships and test the associations with different measures of health. Lack of reciprocity at work is associated with poorer health in a number of studies. However, few studies have analysed the effect of nonreciprocity in other kinds of social relationships on health. The Whitehall II Study is an ongoing prospective study of British civil servants (n=10308 at baseline in 1985-88). Cross-sectional data from the latest phase (7, n=6944 in 2002-04) were used in the analyses. The main exposure was a questionnaire measuring nonreciprocal social relations in partnership, parent-children, and general trusting relationships. Health measures included the SF-36 mental and physical component scores, General Health Questionnaire-30 depression subscale, Jenkins' Sleep disturbance questionnaire, and the Rose Angina questionnaire. Logistic and linear regression models were analysed, adjusted for potential confounders, and mediators of the association. Lack of reciprocity is associated with all measures of poorer health. This association attenuates after adjustment for previous health and additional confounders and mediators but remains significant in a majority of models. Negative social support from a close person is independently associated with reduced health, but adjusting for this effect does not eliminate the association of nonreciprocity with poor health. The effort-reward imbalance at work model has been extended to close and more general social relationships. Lack of reciprocity in partnership, parent-children and general trusting relationships is associated with poorer health.

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

PubMed

Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

2014-06-01

One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 × 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects. The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments.

The association of serum prolactin concentration with inflammatory biomarkers - cross-sectional findings from the population-based Study of Health in Pomerania.

PubMed

Friedrich, Nele; Schneider, Harald J; Spielhagen, Christin; Markus, Marcello Ricardo Paulista; Haring, Robin; Grabe, Hans J; Buchfelder, Michael; Wallaschofski, Henri; Nauck, Matthias

2011-10-01

Prolactin (PRL) is involved in immune regulation and may contribute to an atherogenic phenotype. Previous results on the association of PRL with inflammatory biomarkers have been conflicting and limited by small patient studies. Therefore, we used data from a large population-based sample to assess the cross-sectional associations between serum PRL concentration and high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6 (IL-6), and white blood cell (WBC) count. From the population-based Study of Health in Pomerania (SHIP), a total of 3744 subjects were available for the present analyses. PRL and inflammatory biomarkers were measured. Linear and logistic regression models adjusted for age, sex, body-mass-index, total cholesterol and glucose were analysed. Multivariable linear regression models revealed a positive association of PRL with WBC. Multivariable logistic regression analyses showed a significant association of PRL with increased IL-6 in non-smokers [highest vs lowest quintile: odds ratio 1·69 (95% confidence interval 1·10-2·58), P = 0·02] and smokers [OR 2·06 (95%-CI 1·10-3·89), P = 0·02]. Similar results were found for WBC in non-smokers [highest vs lowest quintile: OR 2·09 (95%-CI 1·21-3·61), P = 0·01)] but not in smokers. Linear and logistic regression analyses revealed no significant associations of PRL with hsCRP or fibrinogen. Serum PRL concentrations are associated with inflammatory biomarkers including IL-6 and WBC, but not hsCRP or fibrinogen. The suggested role of PRL in inflammation needs further investigation in future prospective studies. © 2011 Blackwell Publishing Ltd.

Psychosocial work factors and sleep problems: findings from the French national SIP survey.

PubMed

Chazelle, Emilie; Chastang, Jean-François; Niedhammer, Isabelle

2016-04-01

This study aimed at exploring the cross-sectional and prospective associations between psychosocial work factors and sleep problems. The study population consisted of a national representative sample of the French working population (SIP survey). The sample sizes were 7506 and 3555 for the cross-sectional and prospective analyses. Sleep problems were defined by either sleep disturbances or insufficient sleep duration at least several times a week. Psychosocial work factors included classical (job strain model factors) and emergent factors (recognition, insecurity, role/ethical conflict, emotional demands, work-life imbalance, etc.). Occupational factors related to working time/hours and physical work environment were also included as well as covariates related to factors outside work. Statistical analyses were performed using weighted Poisson regression analysis. In the cross-sectional analyses, psychological demands, low social support, low recognition, emotional demands, perception of danger, work-life imbalance and night work were found to be associated with sleep problems. In the prospective analyses, psychological demands and night work were predictive of sleep problems. Using a less conservative method, more factors were found to be associated with sleep problems. Dose-response associations were observed, showing that the more frequent the exposure to these factors, the higher the risk of sleep problems. No effect of repeated exposure was found on sleep problems. Classical and emergent psychosocial work factors were associated with sleep problems. More prospective studies and prevention policies may be needed.

Quantitative assessment of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and digestive system cancer risk.

PubMed

Wang, J; Yang, S; Guo, F H; Mao, X; Zhou, H; Dong, Y Q; Wang, Z M; Luo, F

2015-11-13

The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been reported to be associated with digestive system cancer; however, the results from previous studies have been conflicting. The present study aimed to investigate the association between the ACE I/D polymorphism and the risk of digestive system cancer using a meta-analysis of previously published studies. Databases were systematically searched to identify relevant studies published prior to December 2014. We estimated the pooled OR with its 95%CI to assess the association. The meta-analysis consisted of thirteen case-control studies that included 2557 patients and 4356 healthy controls. Meta-analysis results based on all the studies showed no significant association between the ACE I/D polymorphism and the risk of digestive system cancer (DD vs II: OR = 0.85, 95%CI = 0.59-1.24; DI vs II: OR = 0.94, 95%CI = 0.78-1.15; dominant model: OR = 0.96, 95%CI = 0.81- 1.15; recessive model: OR = 1.06, 95%CI = 0.76-1.48). Subgroup analyses by race and cancer type did not detect an association between the ACE I/D polymorphism and digestive system cancer risk. However, when the analyses were restricted to smaller studies (N < 500 patients), the summary OR of DI vs II was 0.80 (95%CI = 0.66-0.97). Our analyses detected a possibility of publication bias with a misestimate of the true association by smaller studies. Overall, meta-analysis results suggest the ACE I/D polymorphism might not be associated with susceptibility to digestive system cancer. Further large and well-designed studies are needed to confirm these conclusions.

Investigation of exomic variants associated with overall survival in ovarian cancer

PubMed Central

Ann Chen, Yian; Larson, Melissa C; Fogarty, Zachary C; Earp, Madalene A; Anton-Culver, Hoda; Bandera, Elisa V; Cramer, Daniel; Doherty, Jennifer A; Goodman, Marc T; Gronwald, Jacek; Karlan, Beth Y; Kjaer, Susanne K; Levine, Douglas A; Menon, Usha; Ness, Roberta B; Pearce, Celeste L; Pejovic, Tanja; Rossing, Mary Anne; Wentzensen, Nicolas; Bean, Yukie T; Bisogna, Maria; Brinton, Louise A; Carney, Michael E; Cunningham, Julie M; Cybulski, Cezary; deFazio, Anna; Dicks, Ed M; Edwards, Robert P; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Gore, Martin; Iversen, Edwin S; Jensen, Allan; Johnatty, Sharon E; Lester, Jenny; Lin, Hui-Yi; Lissowska, Jolanta; Lubinski, Jan; Menkiszak, Janusz; Modugno, Francesmary; Moysich, Kirsten B; Orlow, Irene; Pike, Malcolm C; Ramus, Susan J; Song, Honglin; Terry, Kathryn L; Thompson, Pamela J; Tyrer, Jonathan P; van den Berg, David J; Vierkant, Robert A; Vitonis, Allison F; Walsh, Christine; Wilkens, Lynne R; Wu, Anna H; Yang, Hannah; Ziogas, Argyrios; Berchuck, Andrew; Chenevix-Trench, Georgia; Schildkraut, Joellen M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pharoah, Paul D P; Fridley, Brooke L

2016-01-01

Background While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). Methods The primary patient set (Set 1) included 14 independent EOC studies (4293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). Results No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta=1.1E-6, HRSet1=1.17, HRSet2=1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta=1.1E-6; Pcorrected=0.01). Conclusions Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. Impact This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. PMID:26747452

Association between study design and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist.

PubMed

Allareddy, Veerasathpurush; Lee, Min Kyeong; Shah, Andrea; Elangovan, Satheesh; Lin, Chin-Yu

2012-01-01

The scientific community views meta-analyses and systematic reviews, in addition to well-designed randomized controlled clinical trials, as the highest echelon in the continuum of hierarchy of evidence. The objective of this study was to examine the association between different study designs and citation counts of articles published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist. All articles, excluding editorial comments, letters to the editor, commentaries, and special articles, that were published in the American Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist during the years 2004 and 2005 were examined in this study. The number of times an article was cited in the first 24 months after its publication was computed. The PubMed database was used to index the study design of the articles. The association between study design and citation counts was examined using the Kruskal-Wallis test. A multivariable negative binomial regression model was used to examine the association between citation count and study design along with several other confounding variables. A total of 624 articles were selected for analysis. Of these, there were 25 meta-analyses or review articles, 42 randomized clinical trials, 59 clinical trials, 48 animal studies, 64 case reports, and 386 quasiexperimental/miscellaneous study designs. The mean ± SD citation count was 1.04 ± 1.46. Nearly half of the articles (n = 311) were not cited even once during the observation period. Case reports were cited less frequently than meta-analyses or reviews (incident risk ratio, 0.37; 95% confidence interval, 0.19 to 0.72; P = .003), even after adjusting for other independent variables. Among various study designs, meta-analyses and review articles are more likely to be cited in the first 24 months after publication. This study demonstrates the importance of publishing more meta-analyses and review articles for quicker dissemination of research findings.

Anthropometrics and prognosis in diffuse large B-cell lymphoma: a multicentre study of 653 patients.

PubMed

Bendtsen, Mette Dahl; Munksgaard, Peter Svenssen; Severinsen, Marianne Tang; Bekric, Eric; Brieghel, Christian; Nielsen, Kristina Buchardi; Brown, Peter de Nully; Dybkaer, Karen; Johnsen, Hans Erik; Bøgsted, Martin; El-Galaly, Tarec Christoffer

2017-04-01

The impact of body mass index (BMI) and body surface area (BSA) on survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent studies show superior outcomes for overweight and obese patients. A total of 653 R-CHOP(-like)-treated DLBCL patients were included in this retrospective cohort study. Patients, baseline clinicopathologic characteristics and treatment information were retrieved from the Danish Lymphoma Registry. Anthropometric measures were obtained from chemotherapy prescription charts. Underweight (BMI <18.5 kg/m 2 ) was associated with significantly worse progression-free survival (PFS) for male patients only in sex-stratified analyses (HR 3.92, 95% CI: 1.57-9.75, P = 0.003, for males; HR 1.65, 95% CI: 0.90-3.02, P = 0.107, for females). In multivariate analyses, underweight was associated with worse PFS for both sexes (HR 5.34, 95% CI: 2.07-13.79, P = 0.001, for males; HR 2.14, 95% CI: 1.12-4.08, P = 0.021, for females). Similar results were obtained in analyses of overall survival. In crude analyses, BSA <1.8 m 2 was associated with worse PFS for men and women (HR 1.65, 95% CI: 1.03-2.65, P = 0.039, for men; HR 1.62, 95% CI: 1.03-2.56, P = 0.037, for women). In multivariate analyses, however, these associations diminished. Our study demonstrates that underweight DLBCL patients have worse outcomes following R-CHOP as compared to normal as well as overweight patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

2,4-Dichlorophenoxyacetic acid and non-Hodgkin's lymphoma, gastric cancer, and prostate cancer: meta-analyses of the published literature.

PubMed

Goodman, Julie E; Loftus, Christine T; Zu, Ke

2015-08-01

Despite evidence from experimental studies indicating that the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), is not carcinogenic, several epidemiology studies have evaluated links between 2,4-D and cancer. Some suggest that 2,4-D is associated with non-Hodgkin's lymphoma (NHL), gastric cancer, and prostate cancer, but results have been inconsistent. We conducted meta-analyses to evaluate the weight of epidemiology evidence for these cancers. We identified articles from PubMed, Scopus, and TOXLINE databases and reference lists of review articles. We evaluated study quality and calculated summary risk estimates using random effects models. We conducted subgroup and sensitivity analyses when possible. We identified nine NHL, three gastric cancer, and two prostate cancer studies for inclusion in our meta-analyses. We found that 2,4-D was not associated with NHL (relative risk [RR] = 0.97, 95% confidence interval [CI] = 0.77-1.22, I(2) = 28.8%, Pheterogeneity = .19), and this result was generally robust to subgroup and sensitivity analyses. 2,4-D was not associated with gastric (RR = 1.14, 95% CI = 0.62-2.10, I(2) = 54.9%, Pheterogeneity = .11) or prostate cancer (RR = 1.32, 95% CI = 0.37-4.69, I(2) 87.0%, Pheterogeneity = .01). The epidemiology evidence does not support an association between 2,4-D and NHL, gastric cancer, or prostate cancer risk. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Independent associations of dairy and calcium intakes with colorectal cancers in the Adventist Health Study-2 cohort.

PubMed

Tantamango-Bartley, Yessenia; Knutsen, Synnove F; Jaceldo-Siegl, Karen; Fan, Jing; Mashchak, Andrew; Fraser, Gary E

2017-10-01

Results associating dairy and Ca intakes with colorectal cancer (CRC) risk have been mixed. Most previous analyses have suffered from confounding between dairy and Ca intakes. We examined independent associations between these variables, also dairy foods, and CRC incidence in a population with a large range of dairy intakes. Adventist Health Study-2 is a cohort study where subjects were enrolled 2002-2007. Proportional hazard regression analyses were performed to estimate hazard ratios (HR). Regression calibration was used to correct for dietary measurement error. The population lived in all states of the USA. There were 77712 analytic subjects, all of whom were Seventh-day Adventists. Much of their dietary Ca came from non-dairy sources. During a mean follow-up of 7·8 years, 380 incident colon cancer and 111 incident rectal cancer cases were observed. Comparing extreme quintiles of intake in measurement error-corrected analyses, dairy intake (HR=0·31; 95 % CI 0·09, 0·88), independent of total Ca, was inversely related with risk of rectal cancer but gave little indication of association with colon cancer. However, total Ca intake (independent of dairy) was associated with risk of colon cancer (HR=0·55; 95 % CI 0·28, 0·98) and there was little indication of association with rectal cancer. Traditional regression analyses and associations with macronutrients from dairy generally supported these results. Milk intake was also negatively associated with CRC (HR=0·63; 95 % CI 0·43, 0·89). Dairy intake may decrease the risk of rectal cancer, and Ca may reduce risk of colon cancer and CRC.

Physical Activity, Physical Fitness and Leukocyte Telomere Length: the Cardiovascular Health Study.

PubMed Central

Soares-Miranda, Luisa; Imamura, Fumiaki; Siscovick, David; Jenny, Nancy Swords; Fitzpatrick, Annette L; Mozaffarian, Dariush

2015-01-01

Introduction The influence of physical activity (PA) and physical fitness (PF) at older ages on changes in telomere length (TL), repetitive DNA sequences that may mark biologic aging, is not well-established. Few prior studies have been conducted in older adults, these were mainly cross-sectional, and few evaluated PF. Methods We investigated cross-sectional and prospective associations of PA and PF with leukocyte TL among 582 older adults (age 73±5 y at baseline) in the Cardiovascular Health Study, having serial TL measures and PA and PF assessed multiple times. Cross-sectional associations were assessed using multivariable repeated-measures regression, in which cumulatively averaged PA and PF measures were related to TL. Longitudinal analyses assessed cumulatively averaged PA and PF against later changes in TL; and changes in cumulatively averaged PA and PF against changes in TL. Results Cross-sectionally, greater walking distance and chair test performance, but not other PA and PF measures, were each associated with longer TL (p-trend=0.007, 0.04 respectively). In longitudinal analyses, no significant associations of baseline PA and PF with change in TL were observed. In contrast, changes in leisure-time activity and chair test performance were each inversely associated with changes in TL. Conclusions Cross-sectional analyses suggest that greater PA and PF are associated with longer TL. Prospective analyses show that changes in PA and PF are associated with differences in changes in TL. Even later in life, changes in certain PA and PF measures are associated with changes in TL, suggesting that leisure-time activity and fitness could reduce leukocyte telomere attrition among older adults. PMID:26083773

Women's work stress and cortisol levels: a longitudinal study of the association between the psychosocial work environment and serum cortisol.

PubMed

Evolahti, Annika; Hultcrantz, Malou; Collins, Aila

2006-11-01

The aim of the present study was to investigate whether there is an association between serum cortisol and work-related stress, as defined by the demand-control model in a longitudinal design. One hundred ten women aged 47-53 years completed a health questionnaire, including the Swedish version of the Job Content Scale, and participated in a psychological interview at baseline and in a follow-up session 2 years later. Morning blood samples were drawn for analyses of cortisol. Multiple stepwise regression analyses and logistic regression analyses showed that work demands and lack of social support were significantly associated with cortisol. The results of this study showed that negative work characteristics in terms of high demands and low social support contributed significantly to the biological stress levels in middle-aged women. Participation in the study may have served as an intervention, increasing the women's awareness and thus improving their health profiles on follow-up.

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

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

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury. These support the evidence of an association between the rs1801516 polymorphism and acute radiation injuries, encouraging further research of this topic.« less

Alcohol-related morbidity and mortality within siblings.

PubMed

Søndergaard, Grethe; Osler, Merete; Andersen, Anne-Marie Nybo; Andersen, Per Kragh; Dalton, Susanne Oksbjerg; Mortensen, Laust H

2015-03-01

To estimate the association between educational status and alcohol-related somatic and non-somatic morbidity and mortality among full siblings in comparison with non-related individuals. Cohort study. Denmark. Approximately 1.4 million full siblings born in Denmark between 1950 and 1979 were followed from age 28-58 years or censoring due to alcohol-related hospitalization and mortality. Cox regression analyses were used to estimate associations of educational status with alcohol-related outcomes. Results from cohort analyses based on non-related individuals and inter-sibling analyses were compared. A lower educational status was associated with a higher rate of alcohol-related outcomes, especially among the youngest (aged 28-37 years) and individuals born 1970-79. Compared with the cohort analyses, the associations attenuated slightly in the inter-sibling analysis. For example, in the cohort analysis, females with a basic school education born 1970-79 had an increased rate of alcohol-related non-somatic morbidity and mortality [hazard rate ratio (HR) = 4.05, 95% confidence interval (CI) = 3.27-5.02] compared to those with a vocational education. In the inter-sibling analysis, the HR attenuated (HR = 2.66, 95% CI = 1.95-3.63). For alcohol-related somatic outcomes the corresponding figures were HR = 3.47 (95% CI = 2.63-4.58) and HR = 3.36 (95% CI = 2.10-5.38), respectively. In general, the associations were stronger among females than males (aged 28-37) in the analyses of alcohol-related non-somatic outcomes. Health conditions earlier in life explained only a minor part of the associations. The association between educational status and alcohol-related somatic and non-somatic morbidity and mortality is only driven by familial factors to a small degree. © 2014 Society for the Study of Addiction.

Mixed Approach Retrospective Analyses of Suicide and Suicidal Ideation for Brand Compared with Generic Central Nervous System Drugs.

PubMed

Cheng, Ning; Rahman, Md Motiur; Alatawi, Yasser; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, C David; Hansen, Richard A

2018-04-01

Several different types of drugs acting on the central nervous system (CNS) have previously been associated with an increased risk of suicide and suicidal ideation (broadly referred to as suicide). However, a differential association between brand and generic CNS drugs and suicide has not been reported. This study compares suicide adverse event rates for brand versus generic CNS drugs using multiple sources of data. Selected examples of CNS drugs (sertraline, gabapentin, zolpidem, and methylphenidate) were evaluated via the US FDA Adverse Event Reporting System (FAERS) for a hypothesis-generating study, and then via administrative claims and electronic health record (EHR) data for a more rigorous retrospective cohort study. Disproportionality analyses with reporting odds ratios and 95% confidence intervals (CIs) were used in the FAERS analyses to quantify the association between each drug and reported suicide. For the cohort studies, Cox proportional hazards models were used, controlling for demographic and clinical characteristics as well as the background risk of suicide in the insured population. The FAERS analyses found significantly lower suicide reporting rates for brands compared with generics for all four studied products (Breslow-Day P < 0.05). In the claims- and EHR-based cohort study, the adjusted hazard ratio (HR) was statistically significant only for sertraline (HR 0.58; 95% CI 0.38-0.88). Suicide reporting rates were disproportionately larger for generic than for brand CNS drugs in FAERS and adjusted retrospective cohort analyses remained significant only for sertraline. However, even for sertraline, temporal confounding related to the close proximity of black box warnings and generic availability is possible. Additional analyses in larger data sources with additional drugs are needed.

The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies.

PubMed

Beer, Tomasz M; Miller, Kurt; Tombal, Bertrand; Cella, David; Phung, De; Holmstrom, Stefan; Ivanescu, Cristina; Skaltsa, Konstantina; Naidoo, Shevani

2017-12-01

Our exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC). HRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables. In baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78-0.84]) and 21% in PREVAIL (HR 0.79 [0.76-0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84-0.93]) and 10% (HR 0.90 [0.86-0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies. Several baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

Associations of maternal BMI and insulin resistance with the maternal metabolome and newborn outcomes.

PubMed

Sandler, Victoria; Reisetter, Anna C; Bain, James R; Muehlbauer, Michael J; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Lowe, Lynn P; Metzger, Boyd E; Newgard, Christopher B; Scholtens, Denise M; Lowe, William L

2017-03-01

Maternal obesity increases the risk for large-for-gestational-age birth and excess newborn adiposity, which are associated with adverse long-term metabolic outcomes in offspring, probably due to effects mediated through the intrauterine environment. We aimed to characterise the maternal metabolic milieu associated with maternal BMI and its relationship to newborn birthweight and adiposity. Fasting and 1 h serum samples were collected from 400 European-ancestry mothers in the Hyperglycaemia and Adverse Pregnancy Outcome Study who underwent an OGTT at ∼28 weeks gestation and whose offspring had anthropometric measurements at birth. Metabolomics assays were performed using biochemical analyses of conventional clinical metabolites, targeted MS-based measurement of amino acids and acylcarnitines and non-targeted GC/MS. Per-metabolite analyses demonstrated broad associations with maternal BMI at fasting and 1 h for lipids, amino acids and their metabolites together with carbohydrates and organic acids. Similar metabolite classes were associated with insulin resistance with unique associations including branched-chain amino acids. Pathway analyses indicated overlapping and unique associations with maternal BMI and insulin resistance. Network analyses demonstrated collective associations of maternal metabolite subnetworks with maternal BMI and newborn size and adiposity, including communities of acylcarnitines, lipids and related metabolites, and carbohydrates and organic acids. Random forest analyses demonstrated contribution of lipids and lipid-related metabolites to the association of maternal BMI with newborn outcomes. Higher maternal BMI and insulin resistance are associated with broad-based changes in maternal metabolites, with lipids and lipid-related metabolites accounting, in part, for the association of maternal BMI with newborn size at birth.

Dental occlusion and temporomandibular disorders.

PubMed

Stone, J Caitlin; Hannah, Andrew; Nagar, Nathan

2017-10-27

Data sourcesMedline, Scopus and Google Scholar.Study selectionTwo reviewers selected studies independently. English language clinical studies assessing the association between temporomandibular disorders (TMD) and features of dental occlusion were considered.Data extraction and synthesisStudy quality was assessed based on the Newcastle-Ottawa Scale (NOS) and a narrative synthesis was presented.ResultsIn all 25 studies (17 case-control, eight comparative) were included. Overall there was a high variability between occlusal features and TMD diagnosis. Findings were consistent with a lack of clinically relevant association between TMD and dental occlusion. Only two studies were associated with TMD in the majority (≥50%) of single variable analyses in patient populations. Only mediotrusive interferences are associated with TMD in the majority of multiple variable analyses.ConclusionsThe findings support the absence of a disease-specific association, there is no ground to hypothesise a major role for dental occlusion in the pathophysiology of TMDs. Dental clinicians are thus encouraged to move forward and abandon the old-fashioned gnathological paradig.

Single nucleotide polymorphism (SNP) discovery in rainbow trout using restriction site associated DNA (RAD) sequencing of doubled haploids and assessment of polymorphism in a population survey

USDA-ARS?s Scientific Manuscript database

Background: Our goal is to produce a high-throughput SNP genotyping platform for genomic analyses in rainbow trout that will enable fine mapping of QTL, whole genome association studies, genomic selection for improved aquaculture production traits, and genetic analyses of wild populations that aid ...

A Systematic Review and Meta-Analyses of the Association Between Anti-Hypertensive Classes and the Risk of Falls Among Older Adults.

PubMed

Ang, Hui Ting; Lim, Ka Keat; Kwan, Yu Heng; Tan, Pui San; Yap, Kai Zhen; Banu, Zafirah; Tan, Chuen Seng; Fong, Warren; Thumboo, Julian; Ostbye, Truls; Low, Lian Leng

2018-06-23

Falls in individuals aged ≥ 60 years may result in injury, hospitalisation or death. The role of anti-hypertensive medications in falls among older adults is unclear. The objective of this study was to assess the association of six anti-hypertensive medication classes, namely α-blockers (AB), angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), β-blockers (BB), calcium channel blockers (CCB) and diuretics, with the risk of falls, injurious falls or recurrent falls in individuals aged ≥ 60 years compared with non-users. We performed systematic searches in PubMed, EMBASE and CINAHL and included cohort, case-control and cross-sectional studies that investigated the associations between the use of anti-hypertensive medication classes and the risk of falls, injurious falls or recurrent falls in older adults (≥ 60 years) reported in English. We assessed study quality using the Newcastle-Ottawa Scale (NOS). Unadjusted and adjusted odds ratios (ORs) were pooled using random effects model. We performed meta-analyses for each anti-hypertensive medication class and each fall outcome. We also performed sensitivity analyses by pooling studies of high quality and subgroup analyses among studies with an average age of ≥ 80 years. Seventy-eight articles (where 74, 34, 27, 18, 13 and 11 of them examined diuretics, BB, CCB, ACEi, AB and ARB, respectively) met our inclusion and exclusion criteria; we pooled estimates from 60 articles. ACEi [OR 0.85, 95% confidence interval (CI) 0.81-0.89], BB (OR 0.84, 95% CI 0.76-0.93) and CCB (OR 0.81, 95% CI 0.74-0.90) use were associated with a lower risk of injurious falls than in non-users. Results in sensitivity and subgroup analyses were largely consistent. The use of ACEi, BB or CCB among older adults may be associated with a lower risk of injurious falls than non-use.

Birth weight and stuttering: Evidence from three birth cohorts.

PubMed

McAllister, Jan; Collier, Jacqueline

2014-03-01

Previous studies have produced conflicting results with regard to the association between birth weight and developmental stuttering. This study sought to determine whether birth weight was associated with childhood and/or adolescent stuttering in three British birth cohort samples. Logistic regression analyses were carried out on data from the Millenium Cohort Study (MCS), British Cohort Study (BCS70) and National Child Development Study (NCDS), whose initial cohorts comprised over 56,000 individuals. The outcome variables were parent-reported stuttering in childhood or in adolescence; the predictors, based on prior research, were birth weight, sex, multiple birth status, vocabulary score and mother's level of education. Birth weight was analysed both as a categorical variable (low birth weight, <2500g; normal range; high birth weight, ≥4000g) and as a continuous variable. Separate analyses were carried out to determine the impact of birth weight and the other predictors on stuttering during childhood (age 3, 5 and 7 and MCS, BCS70 and NCDS, respectively) or at age 16, when developmental stuttering is likely to be persistent. None of the multivariate analyses revealed an association between birth weight and parent-reported stuttering. Sex was a significant predictor of stuttering in all the analyses, with males 1.6-3.6 times more likely than females to stutter. Our results suggest that birth weight is not a clinically useful predictor of childhood or persistent stuttering. Copyright © 2013 Elsevier Inc. All rights reserved.

Personal use of hair dyes and the risk of bladder cancer: results of a meta-analysis.

PubMed Central

Huncharek, Michael; Kupelnick, Bruce

2005-01-01

OBJECTIVE: This study examined the methodology of observational studies that explored an association between personal use of hair dye products and the risk of bladder cancer. METHODS: Data were pooled from epidemiological studies using a general variance-based meta-analytic method that employed confidence intervals. The outcome of interest was a summary relative risk (RRs) reflecting the risk of bladder cancer development associated with use of hair dye products vs. non-use. Sensitivity analyses were performed to explain any observed statistical heterogeneity and to explore the influence of specific study characteristics of the summary estimate of effect. RESULTS: Initially combining homogenous data from six case-control and one cohort study yielded a non-significant RR of 1.01 (0.92, 1.11), suggesting no association between hair dye use and bladder cancer development. Sensitivity analyses examining the influence of hair dye type, color, and study design on this suspected association showed that uncontrolled confounding and design limitations contributed to a spurious non-significant summary RR. The sensitivity analyses yielded statistically significant RRs ranging from 1.22 (1.11, 1.51) to 1.50 (1.30, 1.98), indicating that personal use of hair dye products increases bladder cancer risk by 22% to 50% vs. non-use. CONCLUSION: The available epidemiological data suggest an association between personal use of hair dye products and increased risk of bladder cancer. PMID:15736329

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

PubMed Central

Christophersen, Ingrid E.; Rienstra, Michiel; Roselli, Carolina; Yin, Xiaoyan; Geelhoed, Bastiaan; Barnard, John; Lin, Honghuang; Arking, Dan E.; Smith, Albert V.; Albert, Christine M.; Chaffin, Mark; Tucker, Nathan R.; Li, Molong; Klarin, Derek; Bihlmeyer, Nathan A; Low, Siew-Kee; Weeke, Peter E.; Müller-Nurasyid, Martina; Smith, J. Gustav; Brody, Jennifer A.; Niemeijer, Maartje N.; Dörr, Marcus; Trompet, Stella; Huffman, Jennifer; Gustafsson, Stefan; Schurman, Claudia; Kleber, Marcus E.; Lyytikäinen, Leo-Pekka; Seppälä, Ilkka; Malik, Rainer; Horimoto, Andrea R. V. R.; Perez, Marco; Sinisalo, Juha; Aeschbacher, Stefanie; Thériault, Sébastien; Yao, Jie; Radmanesh, Farid; Weiss, Stefan; Teumer, Alexander; Choi, Seung Hoan; Weng, Lu-Chen; Clauss, Sebastian; Deo, Rajat; Rader, Daniel J.; Shah, Svati; Sun, Albert; Hopewell, Jemma C.; Debette, Stephanie; Chauhan, Ganesh; Yang, Qiong; Worrall, Bradford B.; Paré, Guillaume; Kamatani, Yoichiro; Hagemeijer, Yanick P.; Verweij, Niek; Siland, Joylene E.; Kubo, Michiaki; Smith, Jonathan D.; Van Wagoner, David R.; Bis, Joshua C.; Perz, Siegfried; Psaty, Bruce M.; Ridker, Paul M.; Magnani, Jared W.; Harris, Tamara B.; Launer, Lenore J.; Shoemaker, M. Benjamin; Padmanabhan, Sandosh; Haessler, Jeffrey; Bartz, Traci M.; Waldenberger, Melanie; Lichtner, Peter; Arendt, Marina; Krieger, Jose E.; Kähönen, Mika; Risch, Lorenz; Mansur, Alfredo J.; Peters, Annette; Smith, Blair H.; Lind, Lars; Scott, Stuart A.; Lu, Yingchang; Bottinger, Erwin B.; Hernesniemi, Jussi; Lindgren, Cecilia M.; Wong, Jorge; Huang, Jie; Eskola, Markku; Morris, Andrew P.; Ford, Ian; Reiner, Alex P.; Delgado, Graciela; Chen, Lin Y.; Chen, Yii-Der Ida; Sandhu, Roopinder K.; Li, Man; Boerwinkle, Eric; Eisele, Lewin; Lannfelt, Lars; Rost, Natalia; Anderson, Christopher D.; Taylor, Kent D.; Campbell, Archie; Magnusson, Patrik K.; Porteous, David; Hocking, Lynne J.; Vlachopoulou, Efthymia; Pedersen, Nancy L.; Nikus, Kjell; Orho-Melander, Marju; Hamsten, Anders; Heeringa, Jan; Denny, Joshua C.; Kriebel, Jennifer; Darbar, Dawood; Newton-Cheh, Christopher; Shaffer, Christian; Macfarlane, Peter W.; Heilmann, Stefanie; Almgren, Peter; Huang, Paul L.; Sotoodehnia, Nona; Soliman, Elsayed Z.; Uitterlinden, Andre G.; Hofman, Albert; Franco, Oscar H.; Völker, Uwe; Jöckel, Karl-Heinz; Sinner, Moritz F.; Lin, Henry J.; Guo, Xiuqing; Dichgans, Martin; Ingelsson, Erik; Kooperberg, Charles; Melander, Olle; Loos, Ruth J. F.; Laurikka, Jari; Conen, David; Rosand, Jonathan; van der Harst, Pim; Lokki, Marja-Liisa; Kathiresan, Sekar; Pereira, Alexandre; Jukema, J. Wouter; Hayward, Caroline; Rotter, Jerome I.; März, Winfried; Lehtimäki, Terho; Stricker, Bruno H.; Chung, Mina K.; Felix, Stephan B.; Gudnason, Vilmundur; Alonso, Alvaro; Roden, Dan M.; Kääb, Stefan; Chasman, Daniel I.; Heckbert, Susan R.; Benjamin, Emelia J.; Tanaka, Toshihiro; Lunetta, Kathryn L.; Lubitz, Steven A.; Ellinor, Patrick T.

2017-01-01

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death.1,2 Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups.3–7 To further define the genetic basis of atrial fibrillation, we performed large-scale, multi-racial meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 18,398 individuals with atrial fibrillation and 91,536 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,806 cases and 132,612 referents. We identified 12 novel genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate new potential targets for drug discovery.8 PMID:28416818

Health care help seeking behaviour among prisoners in Norway.

PubMed

Nesset, Merete Berg; Rustad, Ase-Bente; Kjelsberg, Ellen; Almvik, Roger; Bjørngaard, Johan Håkon

2011-11-04

Prisoners are associated with high health care needs compared with the general population. This study aims to investigate prisoners' use of health service. A cross-sectional study of 29 prisons in central and southern parts of Norway. A questionnaire was distributed to 1, 454 prisoners (90% response rate). Multilevel analyses were employed to analyse help seeking behaviour among the prisoners. Help seeking was substantially associated with sleep problems and drug problems. There was also a tendency for closed prisons as well as high staffing levels of healthcare professionals to be associated with elevated health care use. This study suggests that sleep problems and drug use are most frequently associated with health service use. The differences in health care use between prisons suggest that the implementation of prison health care standards should be addressed.

XPAT: a toolkit to conduct cross-platform association studies with heterogeneous sequencing datasets.

PubMed

Yu, Yao; Hu, Hao; Bohlender, Ryan J; Hu, Fulan; Chen, Jiun-Sheng; Holt, Carson; Fowler, Jerry; Guthery, Stephen L; Scheet, Paul; Hildebrandt, Michelle A T; Yandell, Mark; Huff, Chad D

2018-04-06

High-throughput sequencing data are increasingly being made available to the research community for secondary analyses, providing new opportunities for large-scale association studies. However, heterogeneity in target capture and sequencing technologies often introduce strong technological stratification biases that overwhelm subtle signals of association in studies of complex traits. Here, we introduce the Cross-Platform Association Toolkit, XPAT, which provides a suite of tools designed to support and conduct large-scale association studies with heterogeneous sequencing datasets. XPAT includes tools to support cross-platform aware variant calling, quality control filtering, gene-based association testing and rare variant effect size estimation. To evaluate the performance of XPAT, we conducted case-control association studies for three diseases, including 783 breast cancer cases, 272 ovarian cancer cases, 205 Crohn disease cases and 3507 shared controls (including 1722 females) using sequencing data from multiple sources. XPAT greatly reduced Type I error inflation in the case-control analyses, while replicating many previously identified disease-gene associations. We also show that association tests conducted with XPAT using cross-platform data have comparable performance to tests using matched platform data. XPAT enables new association studies that combine existing sequencing datasets to identify genetic loci associated with common diseases and other complex traits.

Association between Ambient Air Pollution and Diabetes Mellitus in Europe and North America: Systematic Review and Meta-Analysis

PubMed Central

Eze, Ikenna C.; Hemkens, Lars G.; Bucher, Heiner C.; Hoffmann, Barbara; Schindler, Christian; Künzli, Nino; Schikowski, Tamara

2015-01-01

Background Air pollution is hypothesized to be a risk factor for diabetes. Epidemiological evidence is inconsistent and has not been systematically evaluated. Objectives We systematically reviewed epidemiological evidence on the association between air pollution and diabetes, and synthesized results of studies on type 2 diabetes mellitus (T2DM). Methods We systematically searched electronic literature databases (last search, 29 April 2014) for studies reporting the association between air pollution (particle concentration or traffic exposure) and diabetes (type 1, type 2, or gestational). We systematically evaluated risk of bias and role of potential confounders in all studies. We synthesized reported associations with T2DM in meta-analyses using random-effects models and conducted various sensitivity analyses. Results We included 13 studies (8 on T2DM, 2 on type 1, 3 on gestational diabetes), all conducted in Europe or North America. Five studies were longitudinal, 5 cross-sectional, 2 case–control, and 1 ecologic. Risk of bias, air pollution assessment, and confounder control varied across studies. Dose–response effects were not reported. Meta-analyses of 3 studies on PM2.5 (particulate matter ≤ 2.5 μm in diameter) and 4 studies on NO2 (nitrogen dioxide) showed increased risk of T2DM by 8–10% per 10-μg/m3 increase in exposure [PM2.5: 1.10 (95% CI: 1.02, 1.18); NO2: 1.08 (95% CI: 1.00, 1.17)]. Associations were stronger in females. Sensitivity analyses showed similar results. Conclusion Existing evidence indicates a positive association of air pollution and T2DM risk, albeit there is high risk of bias. High-quality studies assessing dose–response effects are needed. Research should be expanded to developing countries where outdoor and indoor air pollution are high. Citation Eze IC, Hemkens LG, Bucher HC, Hoffmann B, Schindler C, Künzli N, Schilowski T, Probst-Hensch NM. 2015. Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis. Environ Health Perspect 123:381–389; http://dx.doi.org/10.1289/ehp.1307823 PMID:25625876

Do smoking and fruit and vegetable intake mediate the association between socio-economic status and plasma carotenoids?

PubMed

Kvaavik, Elisabeth; Totland, Torunn H; Bastani, Nasser; Kjøllesdal, Marte K; Tell, Grethe S; Andersen, Lene F

2014-08-01

The aim was to study whether the association between educational attainment and antioxidant status is mediated by smoking and fruit and vegetable intake. Cross-sectional analyses of the Oslo Youth Study 2006 wave were carried out. Information about education, smoking habits and diet was collected by questionnaire for 261 subjects (142 women and 119 men aged 38-42 years). Blood samples, height and weight measurements were taken by the participants' General Practitioner. Blood were analysed for plasma carotenoids. Linear regression analyses were used to examine whether smoking and fruit and vegetable intake mediate the association between education and plasma carotenoids. Educational level was positively associated with β-cryptoxanthin, α-carotene and lutein/zeaxanthin, but not with total carotenoids, β-carotene or lycopene. Education was negatively associated with smoking and positively associated with fruit and vegetable intake. Smoking was negatively associated with β-cryptoxanthin, and fruit and vegetable intake was positively associated with β-cryptoxanthin (adjusted for educational level). Moreover, cigarette consumption mediated the association between education and β-cryptoxanthin by 37%, while fruit and vegetable intake mediated this association by 18%. The total mediation effect was 55%. Smoking seemed to be more important as a mediator between education and plasma levels of β-cryptoxanthin than the intake of fruit and vegetables, but more studies are needed to establish the relative importance of smoking and diet as mediators of the association between education and antioxidant status. © The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Meta-Analyses of Genome-Wide Association Data Hold New Promise for Addiction Genetics.

PubMed

Agrawal, Arpana; Edenberg, Howard J; Gelernter, Joel

2016-09-01

Meta-analyses of genome-wide association study data have begun to lead to promising new discoveries for behavioral and psychiatrically relevant phenotypes (e.g., schizophrenia, educational attainment). We outline how this methodology can similarly lead to novel discoveries in genomic studies of substance use disorders, and discuss challenges that will need to be overcome to accomplish this goal. We illustrate our approach with the work of the newly established Substance Use Disorders workgroup of the Psychiatric Genomics Consortium.

Genome-wide Association Studies for Female Fertility Traits in Chinese and Nordic Holsteins.

PubMed

Liu, Aoxing; Wang, Yachun; Sahana, Goutam; Zhang, Qin; Liu, Lin; Lund, Mogens Sandø; Su, Guosheng

2017-08-16

Reduced female fertility could cause considerable economic loss and has become a worldwide problem in the modern dairy industry. The objective of this study was to detect quantitative trait loci (QTL) for female fertility traits in Chinese and Nordic Holsteins using various strategies. First, single-trait association analyses were performed for female fertility traits in Chinese and Nordic Holsteins. Second, the SNPs with P-value < 0.005 discovered in Chinese Holsteins were validated in Nordic Holsteins. Third, the summary statistics from single-trait association analyses were combined into meta-analyses to: (1) identify common QTL for multiple fertility traits within each Holstein population; (2) detect SNPs which were associated with a female fertility trait across two Holstein populations. A large numbers of QTL were discovered or confirmed for female fertility traits. The QTL segregating at 31.4~34.1 Mb on BTA13, 48.3~51.9 Mb on BTA23 and 34.0~37.6 Mb on BTA28 shared between Chinese and Nordic Holsteins were further ascertained using a validation approach and meta-analyses. Furthermore, multiple novel variants identified in Chinese Holsteins were validated with Nordic data as well as meta-analyses. The genes IL6R, SLC39A12, CACNB2, ZEB1, ZMIZ1 and FAM213A were concluded to be strong candidate genes for female fertility in Holsteins.

Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity.

PubMed

Revelas, Mary; Thalamuthu, Anbupalam; Oldmeadow, Christopher; Evans, Tiffany-Jane; Armstrong, Nicola J; Kwok, John B; Brodaty, Henry; Schofield, Peter R; Scott, Rodney J; Sachdev, Perminder S; Attia, John R; Mather, Karen A

2018-06-08

Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses. Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts. Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males). In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. Copyright © 2018. Published by Elsevier B.V.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population

PubMed Central

Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei

2016-01-01

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327

Gender Moderates the Association of Depressive Symptoms to Sexual Risk Behavior Among HIV-Positive African-American Outpatients.

PubMed

Babowitch, Jacklyn D; Vanable, Peter A; Carey, Michael P

2018-05-01

Previous research has reported an association between depressive symptoms and sexual risk behavior. The purpose of this study was to explore whether gender moderates this association in a sample of HIV-positive African-Americans. Participants (N = 93) self-reported depressive symptoms (Center for Epidemiological Studies-Depression Scale; CES-D), and sexual risk behavior for the past 4 months. Analyses revealed that the depressive symptoms-by-gender interaction was associated with condomless sex and substance use proximal to sex. When analyses were stratified by gender, depressive symptoms were associated with condomless sex and frequency of substance use only for women. We conclude that depressive symptoms may be a more powerful sexual risk factor among women relative to men.

Sleep disruption, chronotype, shift work, and prostate cancer risk and mortality: a 30-year prospective cohort study of Finnish twins.

PubMed

Dickerman, Barbra A; Markt, Sarah C; Koskenvuo, Markku; Hublin, Christer; Pukkala, Eero; Mucci, Lorelei A; Kaprio, Jaakko

2016-11-01

Sleep disruption and shift work have been associated with cancer risk, but epidemiologic evidence for prostate cancer remains limited. We aimed to prospectively investigate the association between midlife sleep- and circadian-related parameters and later prostate cancer risk and mortality in a population-based cohort of Finnish twins. Data were drawn from the Older Finnish Twin Cohort and included 11,370 twins followed from 1981 to 2012. Over the study period, 602 incident cases of prostate cancer and 110 deaths from prostate cancer occurred. Cox regression was used to evaluate associations between midlife sleep duration, sleep quality, chronotype, and shift work with prostate cancer risk and prostate cancer-specific mortality. Within-pair co-twin analyses were employed to account for potential familial confounding. Compared to "definite morning" types, "somewhat evening" types had a significantly increased risk of prostate cancer (HR 1.3; 95 % CI 1.1, 1.6). Chronotype significantly modified the relationship between shift work and prostate cancer risk (p-interaction <0.001). We found no significant association between sleep duration, sleep quality, or shift work and prostate cancer risk in the overall analyses and no significant association between any sleep- or circadian-related parameter and risk in co-twin analyses. Neither sleep- nor circadian-related parameters were significantly associated with prostate cancer-specific mortality. The association between sleep disruption, chronotype, and shift work with prostate cancer risk and mortality has never before been studied in a prospective study of male twins. Our findings suggest that chronotype may be associated with prostate cancer risk and modify the association between shift work and prostate cancer risk. Future studies of circadian disruption and prostate cancer should account for this individual-level characteristic.

Associations Between Quality of Life and Functioning in an Assertive Community Treatment Population.

PubMed

Clausen, Hanne; Landheim, Anne; Odden, Sigrun; Heiervang, Kristin Sverdvik; Stuen, Hanne Kilen; Killaspy, Helen; Šaltytė Benth, Jurate; Ruud, Torleif

2015-11-01

Level of functioning is positively associated with subjective quality of life for people with severe mental illness, but a detailed relationship between functioning and satisfaction with various life domains is largely unknown, and this gap prompted this study. Demographic and clinical data were obtained from 149 patients engaged with 12 assertive community treatment teams in Norway. Multivariate regression analyses were used to explore associations between subjective quality of life and patient characteristics. Analyses confirmed positive associations between quality of life and age, functioning, and weekly contact with family and friends and a negative association with anxiety and depressive symptoms. Positive associations between several areas of practical and social functioning and satisfaction with related life domains also were found. Although a causal direction of the associations between functioning and life satisfaction has not been determined in this study, the positive findings might indicate that programs aiming to improve functioning could affect patients' quality of life.

Statistical Selection of Biological Models for Genome-Wide Association Analyses.

PubMed

Bi, Wenjian; Kang, Guolian; Pounds, Stanley B

2018-05-24

Genome-wide association studies have discovered many biologically important associations of genes with phenotypes. Typically, genome-wide association analyses formally test the association of each genetic feature (SNP, CNV, etc) with the phenotype of interest and summarize the results with multiplicity-adjusted p-values. However, very small p-values only provide evidence against the null hypothesis of no association without indicating which biological model best explains the observed data. Correctly identifying a specific biological model may improve the scientific interpretation and can be used to more effectively select and design a follow-up validation study. Thus, statistical methodology to identify the correct biological model for a particular genotype-phenotype association can be very useful to investigators. Here, we propose a general statistical method to summarize how accurately each of five biological models (null, additive, dominant, recessive, co-dominant) represents the data observed for each variant in a GWAS study. We show that the new method stringently controls the false discovery rate and asymptotically selects the correct biological model. Simulations of two-stage discovery-validation studies show that the new method has these properties and that its validation power is similar to or exceeds that of simple methods that use the same statistical model for all SNPs. Example analyses of three data sets also highlight these advantages of the new method. An R package is freely available at www.stjuderesearch.org/site/depts/biostats/maew. Copyright © 2018. Published by Elsevier Inc.

Associations between ABO blood groups and biochemical recurrence after radical prostatectomy.

PubMed

Ohno, Yoshio; Ohori, Makoto; Nakashima, Jun; Okubo, Hidenori; Satake, Naoya; Takizawa, Issei; Hashimoto, Takeshi; Hamada, Riu; Nakagami, Yoshihiro; Yoshioka, Kunihiko; Tachibana, Masaaki

2015-01-01

Recent studies have demonstrated associations between ABO blood groups and prognosis in various types of cancers. The aim of this study was to investigate the association between ABO blood groups and biochemical recurrence (BCR) after radical prostatectomy (RP). A total of 555 patients with prostate cancer who underwent RP were included in the study. No patients received neoadjuvant and/or adjuvant therapy. The effect of ABO blood groups on BCR was examined using univariate and multivariate analyses. During the follow-up period (mean, 52.0 months), 166 patients (29.9%) experienced BCR, with a 5-year BCR-free rate of 67.3%. Although the ABO blood group was not a significantly associated with BCR in the univariate analysis, it was an independent predictor of BCR in the multivariate analysis: blood type O patients had a significantly lower risk of BCR compared to type A patients (Hazard ratio, 0.608; 95% confidence interval, 0.410-0.902; P = 0.014). Further analyses revealed that surgical margin status confounded the assessment of the association between the ABO blood group and BCR. In the analyses of patients with a negative surgical margin, the 5-year BCR-free rate in blood type O patients was a significantly higher than that in type A patients (91.2% vs. 71.0%; P = 0.026). Blood type O is significantly associated with a decreased risk of biochemical recurrence after radical prostatectomy. Further studies are needed to clarify the nature of this association.

Intrabreed Stratification Related to Divergent Selection Regimes in Purebred Dogs May Affect the Interpretation of Genetic Association Studies

PubMed Central

Chang, Melanie L.; Yokoyama, Jennifer S.; Branson, Nick; Dyer, Donna J.; Hitte, Christophe; Overall, Karen L.

2009-01-01

Until recently, canine genetic research has not focused on population structure within breeds, which may confound the results of case–control studies by introducing spurious correlations between phenotype and genotype that reflect population history. Intrabreed structure may exist when geographical origin or divergent selection regimes influence the choices of potential mates for breeding dogs. We present evidence for intrabreed stratification from a genome-wide marker survey in a sample of unrelated dogs. We genotyped 76 Border Collies, 49 Australian Shepherds, 17 German Shepherd Dogs, and 17 Portuguese Water Dogs for our primary analyses using Affymetrix Canine v2.0 single-nucleotide polymorphism (SNP) arrays. Subsets of autosomal markers were examined using clustering algorithms to facilitate assignment of individuals to populations and estimation of the number of populations represented in the sample. SNPs passing stringent quality control filters were employed for explicitly phylogenetic analyses reconstructing relationships between individuals using maximum parsimony and Bayesian methods. We used simulation studies to explore the possible effects of intrabreed stratification on genome-wide association studies. These analyses demonstrate significant stratification in at least one of our primary breeds of interest, the Border Collie. Demographic and pedigree data suggest that this population substructure may result from geographic isolation or divergent selection regimes practiced by breeders with different breeding program goals. Simulation studies indicate that such stratification could result in false discovery rates significant enough to confound genome-wide association analyses. Intrabreed stratification should be accounted for when designing and interpreting the results of case–control association studies using purebred dogs.

Variation in narrative identity is associated with trajectories of mental health over several years.

PubMed

Adler, Jonathan M; Turner, Ariana F; Brookshier, Kathryn M; Monahan, Casey; Walder-Biesanz, Ilana; Harmeling, Luke H; Albaugh, Michelle; McAdams, Dan P; Oltmanns, Thomas F

2015-03-01

This article presents 2 longitudinal studies designed to assess the relationship between variability in narrative identity and trajectories of mental health over several years. In Study 1, core scenes from 89 late-mid-life adults' life stories were assessed for several narrative themes. Participants' mental health and physical health were assessed concurrently with the narratives and annually for the subsequent 4 years. Concurrent analyses indicated that the themes of agency, redemption, and contamination were significantly associated with mental health. Longitudinal analyses indicated that these same 3 themes were significantly associated with participants' trajectories of mental health over the course of 4 years. Exploratory analyses indicated that narratives of challenging experiences may be central to this pattern of results. In Study 2, similar longitudinal analyses were conducted on a sample of 27 late-mid-life adults who received a major physical illness diagnosis between the baseline assessment and 6 months later and a matched sample of 27 control participants who remained healthy throughout the study. Participants' mental health and physical health were assessed every 6 months for 2 years. In this study, the themes of agency, communion, redemption, and contamination in participants' life narratives collected at baseline (before any participant became sick) were significantly associated with mental health in the group of participants who went on to receive a medical diagnosis, but not in the control group. Taken together, the results of these 2 studies indicate that the way an individual constructs personal narratives may impact his or her trajectory of mental health over time. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Variation in Narrative Identity is Associated with Trajectories of Mental Health over Several Years

PubMed Central

Adler, Jonathan M.; Turner, Ariana F.; Brookshier, Kathryn M.; Monahan, Casey; Walder-Biesanz, Ilana; Harmeling, Luke H.; Albaugh, Michelle; McAdams, Dan P.; Oltmanns, Thomas F.

2015-01-01

This paper presents two longitudinal studies designed to assess the relationship between variability in narrative identity and trajectories of mental health over several years. In Study 1, core scenes from 89 late-mid-life adults’ life stories were assessed for several narrative themes. Participants’ mental health and physical health were assessed concurrently with the narratives and once a year for the subsequent four years. Concurrent analyses indicated that the themes of agency, redemption, and contamination were significantly associated with mental (but not physical) health. Longitudinal analyses indicated that these same three themes were significantly associated with participants’ trajectories of mental health over the course of four years. Exploratory analyses indicated that narratives of challenging experiences may be central to this pattern of results. In Study 2, similar longitudinal analyses were conducted on a sample of 27 late-mid-life adults who received a major physical illness diagnosis between the baseline assessment and six months later and a matched sample of 27 control participants who remained healthy throughout the study. Participants’ mental health and physical health were assessed every six months for two years. In this tightly controlled study, the themes of agency, communion, redemption, and contamination in participants’ life narratives collected at Baseline (before any participant got sick) were significantly positively associated with mental health in the group of participants who went on to receive a medical diagnosis, but not in the control group. Taken together, the results of these two studies indicate that the way an individual constructs personal narratives may impact his or her trajectory of mental health over time. PMID:25751718

Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

PubMed Central

Lyall, Kristen; Baker, Alice; Hertz-Picciotto, Irva; Walker, Cheryl K.

2013-01-01

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided. PMID:23965925

Night shift work and breast cancer risk: what do the meta-analyses tell us?

PubMed

Pahwa, Manisha; Labrèche, France; Demers, Paul A

2018-05-22

Objectives This paper aims to compare results, assess the quality, and discuss the implications of recently published meta-analyses of night shift work and breast cancer risk. Methods A comprehensive search was conducted for meta-analyses published from 2007-2017 that included at least one pooled effect size (ES) for breast cancer associated with any night shift work exposure metric and were accompanied by a systematic literature review. Pooled ES from each meta-analysis were ascertained with a focus on ever/never exposure associations. Assessments of heterogeneity and publication bias were also extracted. The AMSTAR 2 checklist was used to evaluate quality. Results Seven meta-analyses, published from 2013-2016, collectively included 30 cohort and case-control studies spanning 1996-2016. Five meta-analyses reported pooled ES for ever/never night shift work exposure; these ranged from 0.99 [95% confidence interval (CI) 0.95-1.03, N=10 cohort studies) to 1.40 (95% CI 1.13-1.73, N=9 high quality studies). Estimates for duration, frequency, and cumulative night shift work exposure were scant and mostly not statistically significant. Meta-analyses of cohort, Asian, and more fully-adjusted studies generally resulted in lower pooled ES than case-control, European, American, or minimally-adjusted studies. Most reported statistically significant between-study heterogeneity. Publication bias was not evident in any of the meta-analyses. Only one meta-analysis was strong in critical quality domains. Conclusions Fairly consistent elevated pooled ES were found for ever/never night shift work and breast cancer risk, but results for other shift work exposure metrics were inconclusive. Future evaluations of shift work should incorporate high quality meta-analyses that better appraise individual study quality.

Re-examining the link between prenatal maternal anxiety and child emotional difficulties, using a sibling design.

PubMed

Bekkhus, Mona; Lee, Yunsung; Nordhagen, Rannveig; Magnus, Per; Samuelsen, Sven O; Borge, Anne I H

2018-02-01

Prenatal exposure to maternal anxiety has been associated with child emotional difficulties in a number of epidemiological studies. One key concern, however, is that this link is vulnerable to confounding by pleiotropic genes or environmental family factors. Data on 82 383 mothers and children from the population-based Mother and Child Cohort Study and data on 21 980 siblings were used in this study. Mothers filled out questionnaires for each unique pregnancy, for infant difficulties at 6 months and for emotional difficulties at 36 months. The link between prenatal maternal anxiety and child difficulties were examined using logistic regression analyses and multiple linear regression analyses for the full study sample and the sibling sample. In the conventional full-cohort analyses, prenatal exposure to maternal anxiety was associated with child difficulties at both 6 months [odds ratio (OR) = 2.1 (1.94-2.27)] and 36 months [OR = 2.72 (2.47-2.99)]. The findings were essentially the same whether we examined difficulties at 6 months or at 36 months. However, these associations were no longer present once we controlled for potential social and genetic confounders in the sibling comparison analyses, either at 6 months [OR = 1.32 (0.91-1.90)] or at 36 months [OR = 1.28 (0.63-2.60)]. Findings from multiple regression analyses with continuous measures were essentially the same. Our finding lends little support for there being an independent prenatal effect on child emotional difficulties; rather, our findings suggest that the link between prenatal maternal anxiety and child difficulties could be confounded by pleiotropic genes or environmental family factors. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

PubMed

Vaidya, D; Dobs, A; Gapstur, S M; Golden, S H; Cushman, M; Liu, K; Ouyang, P

2012-12-01

Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

The relationship between body mass index and uric acid: a study on Japanese adult twins.

PubMed

Tanaka, Kentaro; Ogata, Soshiro; Tanaka, Haruka; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo

2015-09-01

The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95 % confidence interval: 0.016-0.373) in men and 0.186 (95 % confidence interval: 0.071-0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95 % confidence interval: 0.072-0.594) in men and 0.314 (95 % confidence interval: 0.151-0.477) in women. The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

Psychological Well-Being and the Human Conserved Transcriptional Response to Adversity

PubMed Central

Fredrickson, Barbara L.; Grewen, Karen M.; Algoe, Sara B.; Firestine, Ann M.; Arevalo, Jesusa M. G.; Ma, Jeffrey; Cole, Steve W.

2015-01-01

Research in human social genomics has identified a conserved transcriptional response to adversity (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of Type I interferon- and antibody-related genes. This report seeks to identify the specific aspects of positive psychological well-being that oppose such effects and predict reduced CTRA gene expression. In a new confirmation study of 122 healthy adults that replicated the approach of a previously reported discovery study, mixed effect linear model analyses identified a significant inverse association between expression of CTRA indicator genes and a summary measure of eudaimonic well-being from the Mental Health Continuum – Short Form. Analyses of a 2- representation of eudaimonia converged in finding correlated psychological and social subdomains of eudaimonic well-being to be the primary carriers of CTRA associations. Hedonic well-being showed no consistent CTRA association independent of eudaimonic well-being, and summary measures integrating hedonic and eudaimonic well-being showed less stable CTRA associations than did focal measures of eudaimonia (psychological and social well-being). Similar results emerged from analyses of pooled discovery and confirmation samples (n = 198). Similar results also emerged from analyses of a second new generalization study of 107 healthy adults that included the more detailed Ryff Scales of Psychological Well-being and found this more robust measure of eudaimonic well-being to also associate with reduced CTRA gene expression. Five of the 6 major sub-domains of psychological well-being predicted reduced CTRA gene expression when analyzed separately, and 3 remained distinctively prognostic in mutually adjusted analyses. All associations were independent of demographic characteristics, health-related confounders, and RNA indicators of leukocyte subset distribution. These results identify specific sub-dimensions of eudaimonic well-being as promising targets for future interventions to mitigate CTRA gene expression, and provide no support for any independent favorable contribution from hedonic well-being. PMID:25811656

Social networks and inflammatory markers in the Framingham Heart Study.

PubMed

Loucks, Eric B; Sullivan, Lisa M; D'Agostino, Ralph B; Larson, Martin G; Berkman, Lisa F; Benjamin, Emelia J

2006-11-01

Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0.03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0.03) and were marginally to modestly associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.

A Discovery Genome-Wide Association Study of Entrepreneurship

ERIC Educational Resources Information Center

Quaye, Lydia; Nicolaou, Nicos; Shane, Scott; Mangino, Massimo

2012-01-01

To identify specific genetic variants influencing the phenotype of entrepreneurship, we conducted a genome-wide association study (GWAS) with 3,933 Caucasian females from the TwinsUK Adult Twin Registry. Following stringent genotype quality control, GWAF (genome-wide association analyses for family data) software was used to assess the association…

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies

PubMed Central

Yu, Lei; Buchman, Aron S.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

2016-01-01

Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10−8) for pathologic AD for all variants. Results: APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67–5.46, p = 1.9 × 10−13), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30–0.61, p = 3.1 × 10−6). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID:27371493

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

PubMed

Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-08-02

To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants. APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

Investigation of 2‐stage meta‐analysis methods for joint longitudinal and time‐to‐event data through simulation and real data application

PubMed Central

Tudur Smith, Catrin; Gueyffier, François; Kolamunnage‐Dona, Ruwanthi

2017-01-01

Background Joint modelling of longitudinal and time‐to‐event data is often preferred over separate longitudinal or time‐to‐event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time‐to‐event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta‐analysis of joint model estimates from multiple studies. Methods We propose a 2‐stage method for meta‐analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta‐analyses of separate longitudinal or time‐to‐event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Results Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta‐analytic setting where association exists between the longitudinal and time‐to‐event outcomes. Conclusions Where evidence of association between longitudinal and time‐to‐event outcomes exists, results from joint models over standalone analyses should be pooled in 2‐stage meta‐analyses. PMID:29250814

Loneliness in older adults is associated with diminished cortisol output.

PubMed

Schutter, N; Holwerda, T J; Stek, M L; Dekker, J J M; Rhebergen, D; Comijs, H C

2017-04-01

Loneliness in older adults has been associated with increased mortality and health problems. One of the assumed underlying mechanisms is dysregulation of the hypothalamic-pituitary-adrenocortical axis (HPA-axis). The purpose of this study was to investigate whether loneliness in older adults is associated with HPA-axis dysregulation and whether this association differs between depressed and non-depressed persons. Cross-sectional data of 426 lonely and non-lonely older adults in the Netherlands Study of Depression in Older Persons (NESDO) were used. Linear regression analyses and multinominal logistic regression analyses were performed to examine the association between loneliness and morning cortisol, cortisol awakening response, diurnal slope and dexamethasone suppression ratio. In all analyses, confounders were introduced. In order to examine whether the association between loneliness and cortisol measures is different in depressed versus non-depressed persons, an interaction term for loneliness x depression diagnosis was tested. Cortisol output in the first hour after awakening and dexamethasone suppression ratio was lower in lonely participants. There were no significant interactions between loneliness and depression diagnosis in the association with the cortisol measures. This study is the first to investigate the association between the HPA-axis and loneliness in a large group of older adults aged 60-93years. We found lower cortisol output in the first hour after awakening and lower dexamethasone suppression ratio in lonely older depressed and non-depressed adults. Whether diminished cortisol output is the underlying mechanism that leads to health problems in lonely older adults is an interesting object for further study. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigating causal associations between use of nicotine, alcohol, caffeine and cannabis: a two-sample bidirectional Mendelian randomization study.

PubMed

Verweij, Karin J H; Treur, Jorien L; Vink, Jacqueline M

2018-07-01

Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine and cannabis use. Two-sample MR was employed to estimate bidirectional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week) and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy. Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these were not supported by the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing. Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine and cannabis use. © 2018 Society for the Study of Addiction.

Empirical Evaluation of Meta-Analytic Approaches for Nutrient and Health Outcome Dose-Response Data

ERIC Educational Resources Information Center

Yu, Winifred W.; Schmid, Christopher H.; Lichtenstein, Alice H.; Lau, Joseph; Trikalinos, Thomas A.

2013-01-01

The objective of this study is to empirically compare alternative meta-analytic methods for combining dose-response data from epidemiological studies. We identified meta-analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta-analyses of odds ratios…

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses.

PubMed

Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

2016-12-01

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses

PubMed Central

Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

2016-01-01

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence. PMID:26728566

Health care help seeking behaviour among prisoners in Norway

PubMed Central

2011-01-01

Background Prisoners are associated with high health care needs compared with the general population. This study aims to investigate prisoners' use of health service. Methods A cross-sectional study of 29 prisons in central and southern parts of Norway. A questionnaire was distributed to 1, 454 prisoners (90% response rate). Multilevel analyses were employed to analyse help seeking behaviour among the prisoners. Results Help seeking was substantially associated with sleep problems and drug problems. There was also a tendency for closed prisons as well as high staffing levels of healthcare professionals to be associated with elevated health care use. Conclusions This study suggests that sleep problems and drug use are most frequently associated with health service use. The differences in health care use between prisons suggest that the implementation of prison health care standards should be addressed. PMID:22053920

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.

PubMed

Morgan, Eileen; Halliday, Sophia R; Campbell, Gemma R; Cardwell, Chris R; Patterson, Chris C

2016-02-01

The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible. A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis. In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors' adjustments for potential confounding made a substantial difference to the pooled ORs. This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Meta-analyses of four polymorphisms of lipoprotein lipase associated with the risk of Alzheimer's disease.

PubMed

Ren, Liang; Ren, Xingxing

2016-04-21

We evaluated the contributions of four polymorphisms of the lipoprotein lipase (LPL) gene to the risk of Alzheimer's disease (AD). Through a comprehensive literature search for genetic variants of LPL involved in AD association studies, we found four polymorphisms for the current meta-analyses. These polymorphisms were Asn291Ser(rs268), PvuII(rs285), HindIII(rs320) and Ser447Ter(rs328). In total, eight studies with 5064 cases and 5016 controls were retrieved for the meta-analyses of the four genetic variants. The analyses showed that Asn291Ser(rs268) (OR=2.34, 95% CI=1.05-5.25, P=0.04), HindIII(rs320) (OR=1.44, 95% CI=1.17-1.78, P=0.0006), and Ser447Ter(rs328) (OR=0.80, 95% CI=0.66-0.98, P=0.03) were significantly associated with a risk of AD. No association was found between the PvuII(rs285) polymorphism and the risk of AD. Our results showed that Asn291Ser(rs268), HindIII(rs320) and Ser447Ter(rs328) polymorphisms of LPL were associated with a risk of AD. Asn291Ser(rs268) and HindIII(rs320) were predisposing factors of AD, whereas Ser447Ter(rs328) showed a protective effect for AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

PubMed

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-09-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

PubMed Central

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-01-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

A field study of discrete emotions: athletes' cognitive appraisals during competition.

PubMed

Martinent, Guillaume; Ferrand, Claude

2015-03-01

Cognitive-motivational-relational theory (CMRT) emphasizes that cognitive appraisal components and core relational themes (in which the 6 separate appraisal judgments are brought together as 1) are the proximal determinants of athletes' emotions. This study aimed to explore appraisals associated with discrete emotions experienced by athletes during competition by adopting a naturalistic, qualitative video-assisted approach. Thirty self-confrontation interviews were conducted with 11 national table-tennis players. Qualitative inductive and deductive content analyses were conducted on the participants' transcripts. Content analyses suggested that primary and secondary appraisal components (goal relevance, goal congruence, ego involvement, blame or credit, coping potential, and future expectations) were associated with a range of positive and negative discrete emotions: self-, other-, and environmental-oriented anger, anxiety, discouragement, disappointment, disgust, joy, serenity, relief, hope, and pride. Hierarchical content analyses also provided some support for the concept of core relational themes. Findings of the present study are consistent with a CMRT approach and highlight that primary and secondary appraisals as well as core relational themes are associated with discrete emotions experienced by athletes while competing. Limitations and practical applications of this study are discussed.

Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.

PubMed

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A

2016-02-01

Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.

Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis

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

Fisk, William J.; Eliseeva, Ekaterina A.; Mendell, Mark J.

Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs)more » and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication bias was evident. Estimated attributable risk proportions ranged from 8% to 20%. Residential dampness and mold are associated with substantial and statistically significant increases in both respiratory infections and bronchitis. If these associations were confirmed as causal, effective control of dampness and mold in buildings would prevent a substantial proportion of respiratory infections.« less

Association of abdominal fat with serum amylase in an older cohort: The Baltimore Longitudinal Study of Aging.

PubMed

Dias, Jenny Pena; Schrack, Jennifer A; Shardell, Michelle D; Egan, Josephine M; Studenski, Stephanie

2016-06-01

Abdominal fat is a major determinant of metabolic diseases in older individuals. Obesity and diabetes are associated with low serum amylase (SA) levels, but the association between SA and metabolic disease is poorly understood. We investigated the association of low SA with diabetes and sex-specific associations of serum amylase with abdominal fat in older adults. In community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (778 participants, age 66.8±13.6years), we assessed abdominal fat by computed tomography and diabetes status using the American Diabetes Association criteria. Linear regression analyses assessed the cross-sectional associations between abdominal fat and SA, and logistic regression assessed the odds of diabetes, given low SA. In unadjusted analyses, individuals in the lowest SA quartile (<48μ/L) had 1.97 greater odds of diabetes, (95%CI, 1.01-3.83) than those in the highest quartile (⩾80μ/L). This association was no longer significant after adjusting for visceral adipose tissue area (VAT, dm(2)), abdominal subcutaneous adipose tissue (SAT, dm(2)) or BMI. In adjusted analyses, VAT and SAT were significantly associated with SA in both sexes. Among women, SA was more strongly associated with VAT than with SAT or BMI; VAT (β=-0.117±0.048, P<0.001), SAT (β=-0.023±0.025, P=0.346) and BMI (β=-0.0052±0.075, P=0.49). The association between SA and diabetes was explained mainly by abdominal visceral fat. In women, SA was more strongly associated with VAT than with BMI or SAT. These findings provide motivation for future mechanistic studies on SA's role in metabolic diseases. Published by Elsevier Ireland Ltd.

Association of abdominal fat with serum amylase in an older cohort: The Baltimore Longitudinal Study of Aging

PubMed Central

Dias, Jenny Pena; Schrack, Jennifer A.; Shardell, Michelle D.; Egan, Josephine M.; Studenski, Stephanie

2018-01-01

Aims Abdominal fat is a major determinant of metabolic diseases in older individuals. Obesity and diabetes are associated with low serum amylase (SA) levels, but the association between SA and metabolic disease is poorly understood. We investigated the association of low SA with diabetes and sex-specific associations of serum amylase with abdominal fat in older adults. Methods In community-dwelling volunteers from the Baltimore Longitudinal Study of Aging (778 participants, age 66.8 ± 13.6 years), we assessed abdominal fat by computed tomography and diabetes status using the American Diabetes Association criteria. Linear regression analyses assessed the cross-sectional associations between abdominal fat and SA, and logistic regression assessed the odds of diabetes, given low SA. Results In unadjusted analyses, individuals in the lowest SA quartile (<48 μ/L) had 1.97 greater odds of diabetes, (95%CI, 1.01–3.83) than those in the highest quartile (≥80 μ/L). This association was no longer significant after adjusting for visceral adipose tissue area (VAT, dm2), abdominal subcutaneous adipose tissue (SAT, dm2) or BMI. In adjusted analyses, VAT and SAT were significantly associated with SA in both sexes. Among women, SA was more strongly associated with VAT than with SAT or BMI; VAT (β = −0.117 ± 0.048, P < 0.001), SAT (β = −0.023 ± 0.025, P = 0.346) and BMI (β = −0.0052 ± 0.075, P = 0.49). Conclusions The association between SA and diabetes was explained mainly by abdominal visceral fat. In women, SA was more strongly associated with VAT than with BMI or SAT. These findings provide motivation for future mechanistic studies on SA’s role in metabolic diseases. PMID:27321338

History of kidney stones and risk of chronic kidney disease: a meta-analysis.

PubMed

Shang, Weifeng; Li, Lixi; Ren, Yali; Ge, Qiangqiang; Ku, Ming; Ge, Shuwang; Xu, Gang

2017-01-01

Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23-1.76])], with significant heterogeneity among these studies ( I 2  = 93.6%, P  < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures.

Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

PubMed Central

Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

2013-01-01

Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

Systematic Review of Health Economic Analyses of Measles and Rubella Immunization Interventions.

PubMed

Thompson, Kimberly M; Odahowski, Cassie L

2016-07-01

Economic analyses for vaccine-preventable diseases provide important insights about the value of prevention. We reviewed the literature to identify all of the peer-reviewed, published economic analyses of interventions related to measles and rubella immunization options to assess the different types of analyses performed and characterize key insights. We searched PubMed, the Science Citation Index, and references from relevant articles for studies in English and found 67 analyses that reported primary data and quantitative estimates of benefit-cost or cost-effectiveness analyses for measles and/or rubella immunization interventions. We removed studies that we characterized as cost-minimization analyses from this sample because they generally provide insights that focused on more optimal strategies to achieve the same health outcome. The 67 analyses we included demonstrate the large economic benefits associated with preventing measles and rubella infections using vaccines and the benefit of combining measles and rubella antigens into a formulation that saves the costs associated with injecting the vaccines separately. Despite the importance of population immunity and dynamic viral transmission, most of the analyses used static models to estimate cases prevented and characterize benefits, although the use of dynamic models continues to increase. Many of the analyses focused on characterizing the most significant adverse outcomes (e.g., mortality for measles, congenital rubella syndrome for rubella) and/or only direct costs, and the most complete analyses present data from high-income countries. © 2014 Society for Risk Analysis.

A meta-analysis of fear-avoidance and pain intensity: The paradox of chronic pain.

PubMed

Kroska, Emily B

2016-10-01

The fear-avoidance model of chronic pain has established avoidance as a predictor of negative outcomes in chronic pain patients. Avoidance, or deliberate attempts to suppress or prevent unwanted experiences (e.g., pain), has been studied extensively, with multiple reviews implicating this behavior as a predictor of disability, physical disuse, and depression. Despite hundreds of studies examining the associations between different components of this model (i.e., catastrophizing, fear, avoidance, depression), the association between fear-avoidance and pain intensity has remained unclear. The present study seeks to clarify this association across samples. The present analyses synthesize the literature (articles from PsycInfo, PubMed, and ProQuest) to determine if fear-avoidance and pain intensity are consistently correlated across studies, samples, and measures. Eligible studies measured pain intensity and fear-avoidance cross-sectionally in chronic pain patients. The search resulted in 118 studies eligible for inclusion. A random-effects model was used to estimate the weighted mean effect size. Comprehensive Meta-Analysis software was used for all analyses. Moderation analyses elucidate the variables that affect the strength of this association. Meta-regression and meta-ANOVA analyses were conducted to examine moderating variables. Moderator variables include demographic characteristics, pain characteristics, study characteristics, and national cultural characteristics (using Hofstede's cultural dimensions). Publication bias was examined using the funnel plot and the p-curve. Results indicate a small-to-moderate positive association between fear-avoidance and pain intensity. The results were stable across characteristics of the sample, including mean age, gender distribution, marital status, and duration of pain. Moderation analyses indicate that the measures utilized and cultural differences affect the strength of this association. Weaker effect sizes were observed for studies that utilized measures of experiential avoidance when compared to studies that utilized pain-specific fear-avoidance measures. Studies that utilized multiple measures of fear-avoidance had stronger effect sizes than studies that utilized a single measure of fear-avoidance. Three of Hofstede's cultural dimensions moderated the association, including Power Distance Index, Individualism versus Collectivism, and Indulgence versus Restraint. The present meta-analysis synthesizes the results from studies examining the association between fear-avoidance and pain intensity among individuals with chronic pain. The positive association indicates that those with increased fear-avoidance have higher pain intensity, and those with higher pain intensity have increased fear-avoidance. Findings indicate that cultural differences and measurement instruments are important to consider in understanding the variables that affect this association. The significant cultural variations may indicate that it is important to consider the function of avoidance behavior in different cultures in an effort to better understand each patient's cultural beliefs, as well as how these beliefs are related to pain and associated coping strategies. The results from the current meta-analysis can be used to inform interventions for patients with chronic pain. In particular, those with more intense pain or increased fear-avoidance should be targeted for prevention and intervention work. Within the intervention itself, avoidance should be undermined and established as an ineffective strategy to manage pain in an effort to prevent disability, depression, and physical deconditioning. Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Association of serum homocysteine with major depressive disorder: results from a large population-based study.

PubMed

Nabi, Hermann; Bochud, Murielle; Glaus, Jennifer; Lasserre, Aurélie M; Waeber, Gérard; Vollenweider, Peter; Preisig, Martin

2013-10-01

Studies on the association between homocysteine levels and depression have shown conflicting results. To examine the association between serum total homocysteine (tHcy) levels and major depressive disorder (MDD) in a large community sample with an extended age range. A total of 3392 men and women aged 35-66 years participating in the CoLaus study and its psychiatric arm (PsyCoLaus) were included in the analyses. High tHcy measured from fasting blood samples was defined as a concentration ≥15μmol/L. MDD was assessed using the semi-structured Diagnostic Interview for Genetics Studies. In multivariate analyses, elevated tHcy levels were associated with greater odds of meeting the diagnostic criteria for lifetime MDD among men (OR=1.71; 95% CI, 1.18-2.50). This was particularly the case for remitted MDD. Among women, there was no significant association between tHcy levels and MDD and the association tended to be in the opposite direction (OR=0.61; 95% CI, 0.34-1.08). In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gene-diet interaction effects on BMI levels in the Singapore Chinese population.

PubMed

Chang, Xuling; Dorajoo, Rajkumar; Sun, Ye; Han, Yi; Wang, Ling; Khor, Chiea-Chuen; Sim, Xueling; Tai, E-Shyong; Liu, Jianjun; Yuan, Jian-Min; Koh, Woon-Puay; van Dam, Rob M; Friedlander, Yechiel; Heng, Chew-Kiat

2018-02-24

Recent genome-wide association studies (GWAS) have identified 97 body-mass index (BMI) associated loci. We aimed to evaluate if dietary intake modifies BMI associations at these loci in the Singapore Chinese population. We utilized GWAS information from six data subsets from two adult Chinese population (N = 7817). Seventy-eight genotyped or imputed index BMI single nucleotide polymorphisms (SNPs) that passed quality control procedures were available in all datasets. Alternative Healthy Eating Index (AHEI)-2010 score and ten nutrient variables were evaluated. Linear regression analyses between z score transformed BMI (Z-BMI) and dietary factors were performed. Interaction analyses were performed by introducing the interaction term (diet x SNP) in the same regression model. Analysis was carried out in each cohort individually and subsequently meta-analyzed using the inverse-variance weighted method. Analyses were also evaluated with a weighted gene-risk score (wGRS) contructed by BMI index SNPs from recent large-scale GWAS studies. Nominal associations between Z-BMI and AHEI-2010 and some dietary factors were identified (P = 0.047-0.010). The BMI wGRS was robustly associated with Z-BMI (P = 1.55 × 10 - 15 ) but not with any dietary variables. Dietary variables did not significantly interact with the wGRS to modify BMI associations. When interaction analyses were repeated using individual SNPs, a significant association between cholesterol intake and rs4740619 (CCDC171) was identified (β = 0.077, adjP interaction  = 0.043). The CCDC171 gene locus may interact with cholesterol intake to increase BMI in the Singaporean Chinese population, however most known obesity risk loci were not associated with dietary intake and did not interact with diet to modify BMI levels.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials.

PubMed

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-11-09

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.

Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

PubMed Central

Sun, Xin; Briel, Matthias; Busse, Jason W; Akl, Elie A; You, John J; Mejza, Filip; Bala, Malgorzata; Diaz-Granados, Natalia; Bassler, Dirk; Mertz, Dominik; Srinathan, Sadeesh K; Vandvik, Per Olav; Malaga, German; Alshurafa, Mohamed; Dahm, Philipp; Alonso-Coello, Pablo; Heels-Ansdell, Diane M; Bhatnagar, Neera; Johnston, Bradley C; Wang, Li; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2009-01-01

Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials. PMID:19900273

"Assessing the methodological quality of systematic reviews in radiation oncology: A systematic review".

PubMed

Hasan, Haroon; Muhammed, Taaha; Yu, Jennifer; Taguchi, Kelsi; Samargandi, Osama A; Howard, A Fuchsia; Lo, Andrea C; Olson, Robert; Goddard, Karen

2017-10-01

The objective of our study was to evaluate the methodological quality of systematic reviews and meta-analyses in Radiation Oncology. A systematic literature search was conducted for all eligible systematic reviews and meta-analyses in Radiation Oncology from 1966 to 2015. Methodological characteristics were abstracted from all works that satisfied the inclusion criteria and quality was assessed using the critical appraisal tool, AMSTAR. Regression analyses were performed to determine factors associated with a higher score of quality. Following exclusion based on a priori criteria, 410 studies (157 systematic reviews and 253 meta-analyses) satisfied the inclusion criteria. Meta-analyses were found to be of fair to good quality while systematic reviews were found to be of less than fair quality. Factors associated with higher scores of quality in the multivariable analysis were including primary studies consisting of randomized control trials, performing a meta-analysis, and applying a recommended guideline related to establishing a systematic review protocol and/or reporting. Systematic reviews and meta-analyses may introduce a high risk of bias if applied to inform decision-making based on AMSTAR. We recommend that decision-makers in Radiation Oncology scrutinize the methodological quality of systematic reviews and meta-analyses prior to assessing their utility to inform evidence-based medicine and researchers adhere to methodological standards outlined in validated guidelines when embarking on a systematic review. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can Preoperative Psychological Assessment Predict Outcomes After Temporomandibular Joint Arthroscopy?

PubMed

Bouloux, Gary F; Zerweck, Ashley G; Celano, Marianne; Dai, Tian; Easley, Kirk A

2015-11-01

Psychological assessment has been used successfully to predict patient outcomes after cardiothoracic and bariatric surgery. The purpose of this study was to determine whether preoperative psychological assessment could be used to predict patient outcomes after temporomandibular joint arthroscopy. Consecutive patients with temporomandibular dysfunction (TMD) who could benefit from arthroscopy were enrolled in a prospective cohort study. All patients completed the Millon Behavior Medicine Diagnostic survey before surgery. The primary predictor variable was the preoperative psychological scores. The primary outcome variable was the difference in pain between the pre- and postoperative periods. The Spearman rank correlation coefficient and the Pearson product-moment correlation were used to determine the association between psychological factors and change in pain. Univariable and multivariable analyses were performed using a mixed-effects linear model and multiple linear regression. A P value of .05 was considered significant. Eighty-six patients were enrolled in the study. Seventy-five patients completed the study and were included in the final analyses. The mean change in visual analog scale (VAS) pain score 1 month after arthroscopy was -15.4 points (95% confidence interval, -6.0 to -24.7; P < .001). Jaw function also improved after surgery (P < .001). No association between change in VAS pain score and each of the 5 preoperative psychological factors was identified with univariable correlation analyses. Multivariable analyses identified that a greater pain decrease was associated with a longer duration of preoperative symptoms (P = .054) and lower chronic anxiety (P = .064). This study has identified a weak association between chronic anxiety and the magnitude of pain decrease after arthroscopy for TMD. Further studies are needed to clarify the role of chronic anxiety in the outcome after surgical procedures for the treatment of TMD. Copyright © 2015. Published by Elsevier Inc.

An analytic study on bounds for the associated Legendre functions. [for truncation of geopotential series in spherical harmonics in orbital analyses

NASA Technical Reports Server (NTRS)

Payne, M. H.

1973-01-01

The bounds for the normalized associated Legendre functions P sub nm were studied to provide a rational basis for the truncation of the geopotential series in spherical harmonics in various orbital analyses. The conjecture is made that the largest maximum of the normalized associated Legendre function lies in the interval which indicates the greatest integer function. A procedure is developed for verifying this conjecture. An on-line algebraic manipulator, IAM, is used to implement the procedure and the verification is carried out for all n equal to or less than 2m, for m = 1 through 6. A rigorous proof of the conjecture is not available.

Astronomy sortie mission definition study. Addendum: Follow-on analyses

NASA Technical Reports Server (NTRS)

1973-01-01

Results of design analyses, trade studies, and planning data of the Astronomy Sortie Mission Definition Study are presented. An in-depth analysis of UV instruments, nondeployed solar payload, and on-orbit access is presented. Planning data are considered, including the cost and schedules associated with the astronomy instruments and/or support hardware. Costs are presented in a parametric fashion.

Nature, Nurture, and Cancer Risks: Genetic and Nutritional Contributions to Cancer.

PubMed

Theodoratou, Evropi; Timofeeva, Maria; Li, Xue; Meng, Xiangrui; Ioannidis, John P A

2017-08-21

It is speculated that genetic variants are associated with differential responses to nutrients (known as gene-diet interactions) and that these variations may be linked to different cancer risks. In this review, we critically evaluate the evidence across 314 meta-analyses of observational studies and randomized controlled trials of dietary risk factors and the five most common cancers (breast, lung, prostate, colorectal, and stomach). We also critically evaluate the evidence across 13 meta-analyses of observational studies of gene-diet interactions for the same cancers. Convincing evidence for association was found only for the intake of alcohol and whole grains in relation to colorectal cancer risk. Three nutrient associations had highly suggestive evidence and another 15 associations had suggestive evidence. Among the examined gene-diet interactions, only one had moderately strong evidence.

No association between posture and musculoskeletal complaints in a professional bassist sample.

PubMed

Woldendorp, K H; Boonstra, A M; Tijsma, A; Arendzen, J H; Reneman, M F

2016-03-01

Professional musicians receive little attention in pain medicine despite reports of high prevalence of musculoskeletal complaints. This study aims to investigate the association between work-related postures and musculoskeletal complaints of professional bass players. Participants were 141 professional and professional student double bassists and bass guitarists. Data about self-reported functioning, general and mental health status, location and intensity of musculoskeletal complaints and psychosocial distress were collected online with self constructed and existing questionnaires. Logistic regression analyses were performed to analyse associations between work-related postural stress (including type of instrument and accompanying specific exposures) and physical complains, adjusted for potential confounders. Logistic regression analyses revealed no association between complaints and the playing position of the left shoulder area in double bassists (p = 0.30), the right wrist area in the bass guitarists (p = 0.70), the right wrist area for the German versus French bowing style (p = 0.59). All three hypotheses were rejected. This study shows that in this sample of professional bass players' long-lasting exposures to postural stress were not associated with musculoskeletal complaints. This challenges a dominant model in pain medicine to focus on ergonomic postures. © 2015 European Pain Federation - EFIC®

No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis.

PubMed

Loley, Christina; Alver, Maris; Assimes, Themistocles L; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C; Kanoni, Stavroula; Kleber, Marcus E; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S; Beutner, Frank; Bottinger, Erwin P; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B; Hall, Alistair S; Hamsten, Anders; Hazen, Stanley L; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K E; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P; Nikus, Kjell; Pedersen, Nancy; Rallidis, Loukianos; Salomaa, Veikko; Shah, Svati H; Stewart, Alexandre F R; Thompson, John R; Zalloua, Pierre A; Chambers, John C; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J; Kooner, Jaspal S; Lehtimäki, Terho; Loos, Ruth J F; März, Winfried; McPherson, Ruth; Metspalu, Andres; Reilly, Muredach P; Ripatti, Samuli; Sanghera, Dharambir K; Thiery, Joachim; Watkins, Hugh; Deloukas, Panos; Kathiresan, Sekar; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; König, Inke R

2016-10-12

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication

PubMed Central

Rijlaarsdam, Jolien; Pappa, Irene; Walton, Esther; Bakermans-Kranenburg, Marian J.; Mileva-Seitz, Viara R.; Rippe, Ralph C.A.; Roza, Sabine J.; Jaddoe, Vincent W.V.; Verhulst, Frank C.; Felix, Janine F.; Cecil, Charlotte A.M.; Relton, Caroline L.; Gaunt, Tom R.; McArdle, Wendy; Mill, Jonathan; Barker, Edward D.; Tiemeier, Henning; van IJzendoorn, Marinus H.

2016-01-01

ABSTRACT Prenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal = 1,740) revealed no epigenome-wide (meta P <1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P <1.00e-04) indicated an over-representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P <1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies. PMID:26889969

Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children.

PubMed

Gazolla, Fernanda Mussi; Neves Bordallo, Maria Alice; Madeira, Isabel Rey; de Miranda Carvalho, Cecilia Noronha; Vieira Monteiro, Alexandra Maria; Pinheiro Rodrigues, Nádia Cristina; Borges, Marcos Antonio; Collett-Solberg, Paulo Ferrez; Muniz, Bruna Moreira; de Oliveira, Cecilia Lacroix; Pinheiro, Suellen Martins; de Queiroz Ribeiro, Rebeca Mathias

2015-05-01

Early exposure to cardiovascular risk factors creates a chronic inflammatory state that could damage the endothelium followed by thickening of the carotid intima-media. To investigate the association of cardiovascular risk factors and thickening of the carotid intima. Media in prepubertal children. In this cross-sectional study, carotid intima-media thickness (cIMT) and cardiovascular risk factors were assessed in 129 prepubertal children aged from 5 to 10 year. Association was assessed by simple and multivariate logistic regression analyses. In simple logistic regression analyses, body mass index (BMI) z-score, waist circumference, and systolic blood pressure (SBP) were positively associated with increased left, right, and average cIMT, whereas diastolic blood pressure was positively associated only with increased left and average cIMT (p<0.05). In multivariate logistic regression analyses increased left cIMT was positively associated to BMI z-score and SBP, and increased average cIMT was only positively associated to SBP (p<0.05). BMI z-score and SBP were the strongest risk factors for increased cIMT.

Effects of Psychological and Social Work Factors on Self-Reported Sleep Disturbance and Difficulties Initiating Sleep.

PubMed

Vleeshouwers, Jolien; Knardahl, Stein; Christensen, Jan Olav

2016-04-01

This prospective cohort study examined previously underexplored relations between psychological/social work factors and troubled sleep in order to provide practical information about specific, modifiable factors at work. A comprehensive evaluation of a range of psychological/social work factors was obtained by several designs; i.e., cross-sectional analyses at baseline and follow-up, prospective analyses with baseline predictors (T1), prospective analyses with average exposure across waves as predictor ([T1 + T2] / 2), and prospective analyses with change in exposure from baseline to follow-up as predictor. Participants consisted of a sample of Norwegian employees from a broad spectrum of occupations, who completed a questionnaire at two points in time, approximately two years apart. Cross-sectional analyses at T1 comprised 7,459 participants, cross-sectional analyses at T2 included 6,688 participants. Prospective analyses comprised a sample 5,070 of participants who responded at both T1 and T2. Univariable and multivariable ordinal logistic regressions were performed. Thirteen psychological/social work factors and two aspects of troubled sleep, namely difficulties initiating sleep and disturbed sleep, were studied. Ordinal logistic regressions revealed statistically significant associations for all psychological and social work factors in at least one of the analyses. Psychological and social work factors predicted sleep problems in the short term as well as the long term. All work factors investigated showed statistically significant associations with both sleep items, however quantitative job demands, decision control, role conflict, and support from superior were the most robust predictors and may therefore be suitable targets of interventions aimed at improving employee sleep. © 2016 Associated Professional Sleep Societies, LLC.

The importance and pitfalls of correlational science in palliative care research.

PubMed

Klepstad, Pål; Kaasa, Stein

2012-12-01

Correlational science discovers associations between patient characteristics, symptoms and biomarkers. Correlational science using data from cross-sectional studies is the most frequently applied study design in palliative care research. The purpose of this review is to address the importance and potential pitfalls in correlational science. Associations observed in correlational science studies can be the basis for generating hypotheses that can be tested in experimental studies and are the basic data needed to develop classification systems that can predict patient outcomes. Major pitfalls in correlational science are that associations do not equate with causality and that statistical significance does not necessarily equal a correlation that is of clinical interest. Researchers should be aware of the end-points that are clinically relevant, that end-points should be defined before the start of the analyses, and that studies with several end-points should account for multiplicity. Correlational science in palliative care research can identify related clinical factors and biomarkers. Interpretation of identified associations should be done with careful consideration of the limitations underlying correlational analyses.

Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies.

PubMed

E, Meng; Yu, Sufang; Dou, Jianrui; Jin, Wu; Cai, Xiang; Mao, Yiyang; Zhu, Daojian; Yang, Rumei

2016-08-01

The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.

The impact of sleep disorders on driving safety-findings from the Second Strategic Highway Research Program naturalistic driving study.

PubMed

Liu, Shu-Yuan; Perez, Miguel A; Lau, Nathan

2018-04-01

This study investigated the association between driving safety and seven sleep disorders amongst 3541 participants of the Second Strategic Highway Research Program (SHRP 2) naturalistic driving study. SHRP 2 collected naturalistic driving data from participants between 16 and 98 years old by instrumenting participants' vehicles. The analyses used logistic regression to determine the likelihood of crash or near-crash involvement, Poisson log-linear regression to assess crash or near-crash rate, and ordinal logistic regression to assess driver maneuver appropriateness and crash or near-crash severity. These analyses did not account for any medical treatments for the sleep disorders. Females with restless legs syndrome/Willis-Ekbom disease (RLS/WED), drivers with insomnia or narcolepsy, are associated with significantly higher risk of crash or near-crash. Drivers with shift work sleep disorder (SWSD) are associated with significantly increased crash or near-crash rate. Females with RLS/WED or sleep apnea and drivers with SWSD are associated with less safe driver maneuver and drivers with periodic limb movement disorder are associated with more severe events. The four analyses provide no evidence of safety decrements associated with migraine. This study is the first examination on the association between seven sleep disorders and different measures of driving risk using large-scale naturalistic driving study data. The results corroborate much of the existing simulator and epidemiological research related to sleep-disorder patients and their driving safety, but add ecological validity to those findings. These results contribute to the empirical basis for medical professionals, policy makers, and employers in making decisions to aid individuals with sleep disorders in balancing safety and personal mobility.

77 FR 8298 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... a quantitative, comprehensive or even representative survey or study of the burdens associated with... existing registered money market fund: Documentation of credit risk analyses, and determinations regarding... for documentation of credit analyses and other determinations) = 2340 responses. (30 funds x 12...

Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

PubMed

Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

2015-04-14

As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

Childhood trauma and problem behavior: Examining the mediating roles of experiential avoidance and mindfulness processes.

PubMed

Roche, Anne I; Kroska, Emily B; Miller, Michelle L; Kroska, Sydney K; O'Hara, Michael W

2018-03-22

Childhood trauma is associated with a variety of risky, unhealthy, or problem behaviors. The current study aimed to explore experiential avoidance and mindfulness processes as mechanisms through which childhood trauma and problem behavior are linked in a college sample. The sample consisted of college-aged young adults recruited November-December, 2016 (N = 414). Participants completed self-report measures of childhood trauma, current problem behavior, experiential avoidance, and mindfulness processes. Bootstrapped mediation analyses examined the mechanistic associations of interest. Mediation analyses indicated that experiential avoidance was a significant mediator of the association between childhood trauma and problem behavior. Additionally, multiple mediation analyses indicated that specific mindfulness facets-act with awareness and nonjudgment of inner experience-significantly mediated the same association. Interventions for college students who have experienced childhood trauma might profitably target mechanisms such as avoidance and mindfulness in order to minimize engagement in problem behavior.

Red and processed meat consumption and gastric cancer risk: a systematic review and meta-analysis

PubMed Central

Zhao, Zhanwei; Yin, Zifang; Zhao, Qingchuan

2017-01-01

The associations between red and processed meat consumption and gastric cancer risk have remained inconclusive. We performed a systematic review and meta-analysis to analyze these associations. We searched PubMed and EMBASE to identify studies published from inception through October 2016. Subtype analyses of gastric cancer (gastric cardia adenocarcinoma and gastric non-cardiac adenocarcinoma) and dose-response analyses were performed. We finally selected 42 eligible studies. The summary relative risks of highest versus lowest consumption were positive for case-control studies with 1.67 (1.36-2.05) for red meat and 1.76 (1.51-2.05) for processed meat, but negative for cohort studies with 1.14 (0.97-1.34) for red meat and 1.23 (0.98-1.55) for processed meat. Subtype analyses of cohort studies suggested null results for gastric cardia adenocarcinoma (red meat, P = 0.79; processed meat, P = 0.89) and gastric non-cardiac adenocarcinoma (red meat, P = 0.12; processed meat, P = 0.12). In conclusion, the present analysis suggested null results between red and processed meat consumption and gastric cancer risk in cohort studies, although case-control studies yielded positive associations. Further well-designed prospective studies are needed to validate these findings. PMID:28430644

The transformative potential of an integrative approach to pregnancy.

PubMed

Eidem, Haley R; McGary, Kriston L; Capra, John A; Abbot, Patrick; Rokas, Antonis

2017-09-01

Complex traits typically involve diverse biological pathways and are shaped by numerous genetic and environmental factors. Pregnancy-associated traits and pathologies are further complicated by extensive communication across multiple tissues in two individuals, interactions between two genomes-maternal and fetal-that obscure causal variants and lead to genetic conflict, and rapid evolution of pregnancy-associated traits across mammals and in the human lineage. Given the multi-faceted complexity of human pregnancy, integrative approaches that synthesize diverse data types and analyses harbor tremendous promise to identify the genetic architecture and environmental influences underlying pregnancy-associated traits and pathologies. We review current research that addresses the extreme complexities of traits and pathologies associated with human pregnancy. We find that successful efforts to address the many complexities of pregnancy-associated traits and pathologies often harness the power of many and diverse types of data, including genome-wide association studies, evolutionary analyses, multi-tissue transcriptomic profiles, and environmental conditions. We propose that understanding of pregnancy and its pathologies will be accelerated by computational platforms that provide easy access to integrated data and analyses. By simplifying the integration of diverse data, such platforms will provide a comprehensive synthesis that transcends many of the inherent challenges present in studies of pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies.

PubMed

Guo, Jing; Astrup, Arne; Lovegrove, Julie A; Gijsbers, Lieke; Givens, David I; Soedamah-Muthu, Sabita S

2017-04-01

With a growing number of prospective cohort studies, an updated dose-response meta-analysis of milk and dairy products with all-cause mortality, coronary heart disease (CHD) or cardiovascular disease (CVD) have been conducted. PubMed, Embase and Scopus were searched for articles published up to September 2016. Random-effect meta-analyses with summarised dose-response data were performed for total (high-fat/low-fat) dairy, milk, fermented dairy, cheese and yogurt. Non-linear associations were investigated using the spine models and heterogeneity by subgroup analyses. A total of 29 cohort studies were available for meta-analysis, with 938,465 participants and 93,158 mortality, 28,419 CHD and 25,416 CVD cases. No associations were found for total (high-fat/low-fat) dairy, and milk with the health outcomes of mortality, CHD or CVD. Inverse associations were found between total fermented dairy (included sour milk products, cheese or yogurt; per 20 g/day) with mortality (RR 0.98, 95% CI 0.97-0.99; I 2  = 94.4%) and CVD risk (RR 0.98, 95% CI 0.97-0.99; I 2  = 87.5%). Further analyses of individual fermented dairy of cheese and yogurt showed cheese to have a 2% lower risk of CVD (RR 0.98, 95% CI 0.95-1.00; I 2  = 82.6%) per 10 g/day, but not yogurt. All of these marginally inverse associations of totally fermented dairy and cheese were attenuated in sensitivity analyses by removing one large Swedish study. This meta-analysis combining data from 29 prospective cohort studies demonstrated neutral associations between dairy products and cardiovascular and all-cause mortality. For future studies it is important to investigate in more detail how dairy products can be replaced by other foods.

Lifestyle and emotional well-being in men and women with type 2 diabetes (e-VitaDM-4; ZODIAC-48).

PubMed

Hendriks, Steven H; van Soldt, Evelien G W; van Vugt, Michael; Groenier, Klaas H; Roelofsen, Yvonne; Maas, Angela H E M; Bilo, Henk J G; Kleefstra, Nanne; van Hateren, Kornelis J J

2017-12-01

Whether lifestyle is associated with well-being in patients with type 2 diabetes (T2D) is largely unknown. Uncovering and clarifying associations between these constructs may lead to new strategies for improving both. The aim was to investigate the relationship between lifestyle and well-being, focussing on gender differences. This cross-sectional study included 1085 patients with T2D that participated in the e-Vita part of the Zwolle outpatient diabetes project integrating available care (ZODIAC) study. Patients were included from May 2012 until September 2014 from 52 general practices. Emotional well-being was assessed with the World Health Organization-5 well-being index (WHO-5). Lifestyle information on body mass index, smoking, physical activity and alcohol use was extracted from self-reported questionnaires. Multiple linear regression analyses were used. After adjustment for other lifestyle factors, physical activity, smoking and drinking 22-35 alcohol consumptions per week were associated with the WHO-5 score in men and physical activity and smoking were associated with the WHO-5 score in women. In the fully adjusted analyses for the total study population, physical activity and smoking were still associated with the WHO-5 score (b = 1.1, P < .001 and b =-3.1, P = .018, respectively). In the fully adjusted analyses stratified to gender only physical activity was associated with the WHO-5 score (in men: b =0.8, P = .006, in women: b = 1.4, P = .001). This study shows a negative, non-clinically relevant association between smoking and emotional well-being in the total population with T2D and a positive, non-clinically relevant association between physical activity and emotional well-being in both men and women with T2D.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

PubMed Central

Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

2015-01-01

BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

The built environment and physical activity levels: the Harvard Alumni Health Study.

PubMed

Lee, I-Min; Ewing, Reid; Sesso, Howard D

2009-10-01

Physical activity is associated with better health, but many individuals are insufficiently active. Modifying the built environment may be an approach capable of influencing population-wide levels of physical activity, but few data exist from longitudinal studies that can minimize bias from active people choosing activity-friendly neighborhoods. This study aims to examine cross-sectional and longitudinal associations between the built environment and physical activity on a large scale. This study examined cross-sectional associations between urban sprawl (mapping addresses to corresponding counties) and physical activity (self-reported) among men throughout the U.S. in 1993 and in 1988, and longitudinal associations between changes in exposure to urban sprawl for movers and physical activity, 1988-1993. Included were 4997 men (mean age, 70 years) in the 1993 cross-sectional study; 4918 men in the 1988 cross-sectional study; and 3448 men in the longitudinal study, 1988-1993. Data were collected prospectively in 1988 and 1993, and analyses were performed in 2007-2008. In cross-sectional analyses, less sprawl was significantly associated with more walking OR, comparing least with most sprawling areas, for meeting physical activity recommendations by walking=1.38 [95% CI=1.09, 1.76] in 1993 and 1.53 [1.19, 1.96] in 1988). Less sprawl also was associated with lower prevalence of overweight (corresponding OR=0.79 [0.64, 0.98] in 1993 and 0.81 [0.66, 1.00] in 1988). However, longitudinal analyses assessing change did not show that decreasing sprawl was associated with increased physical activity or decreased BMI. These findings suggest that the cross-sectional results may reflect self-selection, rather than indicating that the built environment--as measured by urban sprawl--increases physical activity. However, the longitudinal findings were limited by small numbers of men changing residence and associated sprawl levels.

Association between month of birth and melanoma risk: fact or fiction?

PubMed

Fiessler, Cornelia; Pfahlberg, Annette B; Keller, Andrea K; Radespiel-Tröger, Martin; Uter, Wolfgang; Gefeller, Olaf

2017-04-01

Evidence on the effect of ultraviolet radiation (UVR) exposure in infancy on melanoma risk in later life is scarce. Three recent studies suggest that people born in spring carry a higher melanoma risk. Our study aimed at verifying whether such a seasonal pattern of melanoma risk actually exists. Data from the population-based Cancer Registry Bavaria (CRB) on the birth months of 28 374 incident melanoma cases between 2002 and 2012 were analysed and compared with data from the Bavarian State Office for Statistics and Data Processing on the birth month distribution in the Bavarian population. Crude and adjusted analyses using negative binomial regression models were performed in the total study group and supplemented by several subgroup analyses. In the crude analysis, the birth months March-May were over-represented among melanoma cases. Negative binomial regression models adjusted only for sex and birth year revealed a seasonal association between melanoma risk and birth month with 13-21% higher relative incidence rates for March, April and May compared with the reference December. However, after additionally adjusting for the birth month distribution of the Bavarian population, these risk estimates decreased markedly and no association with the birth month was observed any more. Similar results emerged in all subgroup analyses. Our large registry-based study provides no evidence that people born in spring carry a higher risk for developing melanoma in later life and thus lends no support to the hypothesis of higher UVR susceptibility during the first months of life. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Association between childhood trauma and accelerated telomere erosion in adulthood: A meta-analytic study.

PubMed

Li, Zongchang; He, Ying; Wang, Dong; Tang, Jingsong; Chen, Xiaogang

2017-10-01

Childhood trauma has long-term sequelae on health status and contributes to numbers of somatic and mental disorders in later life. Findings from experimental studies in animals suggest that telomere erosion may be a mediator of this relationship. However, results from human studies are heterogeneous. To address these inconsistencies, we performed a meta-analysis regarding the association between childhood trauma and telomere length in adulthood. Articles were identified by systematically searching the Medline, EMBASE and Web of Science databases. Twenty four studies, which include twenty six sample sets and 30,919 participants, met the inclusion criteria for meta-analyses. This meta-analyses revealed that individuals experienced childhood trauma have accelerated telomere erosion in adulthood, with a small effect size (r = -0.05, 95% CI = -0.08-0.03, p < 0.001). Subgroup analyses by type of childhood trauma revealed a trend in difference between groups (Q = 5.24, p = 0.07). Analyses for individual trauma types revealed a significant association between childhood separation and telomere erosion (r = -0.09, p < 0.001), but not for physical abuse, sexual abuse and loss of a parent. This meta-analysis demonstrated a significant association between childhood trauma and accelerated telomere erosion in adulthood, and further revealed that different trauma types have various impacts on telomere. Additional research on the mechanism that links the individual types of childhood trauma with telomere is needed in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of 2-stage meta-analysis methods for joint longitudinal and time-to-event data through simulation and real data application.

PubMed

Sudell, Maria; Tudur Smith, Catrin; Gueyffier, François; Kolamunnage-Dona, Ruwanthi

2018-04-15

Joint modelling of longitudinal and time-to-event data is often preferred over separate longitudinal or time-to-event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time-to-event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta-analysis of joint model estimates from multiple studies. We propose a 2-stage method for meta-analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta-analyses of separate longitudinal or time-to-event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta-analytic setting where association exists between the longitudinal and time-to-event outcomes. Where evidence of association between longitudinal and time-to-event outcomes exists, results from joint models over standalone analyses should be pooled in 2-stage meta-analyses. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Race/Ethnicity and the Pharmacogenetics of Reported Suicidality With Efavirenz Among Clinical Trials Participants.

PubMed

Mollan, Katie R; Tierney, Camlin; Hellwege, Jacklyn N; Eron, Joseph J; Hudgens, Michael G; Gulick, Roy M; Haubrich, Richard; Sax, Paul E; Campbell, Thomas B; Daar, Eric S; Robertson, Kevin R; Ventura, Diana; Ma, Qing; Edwards, Digna R Velez; Haas, David W

2017-09-01

We examined associations between suicidality and genotypes that predict plasma efavirenz exposure among AIDS Clinical Trials Group study participants in the United States. Four clinical trials randomly assigned treatment-naive participants to efavirenz-containing regimens; suicidality was defined as reported suicidal ideation or attempted or completed suicide. Genotypes that predict plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms. Associations were evaluated with weighted Cox proportional hazards models stratified by race/ethnicity. Additional analyses adjusted for genetic ancestry and selected covariates. Among 1833 participants, suicidality was documented in 41 in exposed analyses, and 34 in on-treatment analyses. In unadjusted analyses based on 12 genotype levels, suicidality increased per level in exposed (hazard ratio, 1.11; 95% confidence interval, .96-1.27) and on-treatment 1.16; 1.01-1.34) analyses. In the on-treatment analysis, the association was strongest among white but nearly null among black participants. Considering 3 metabolizer levels (extensive, intermediate and slow), slow metabolizers were at increased risk. Results were similar after baseline covariate-adjustment for genetic ancestry, sex, age, weight, injection drug use history, and psychiatric history or recent psychoactive medication. Genotypes that predict higher plasma efavirenz exposure were associated with increased risk of suicidality. Strength of association varied by race/ethnicity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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.

Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.

PubMed

Ameling, Sabine; Kacprowski, Tim; Chilukoti, Ravi Kumar; Malsch, Carolin; Liebscher, Volkmar; Suhre, Karsten; Pietzner, Maik; Friedrich, Nele; Homuth, Georg; Hammer, Elke; Völker, Uwe

2015-10-14

Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.

Review of nutritional screening and assessment tools and clinical outcomes in heart failure.

PubMed

Lin, Hong; Zhang, Haifeng; Lin, Zheng; Li, Xinli; Kong, Xiangqin; Sun, Gouzhen

2016-09-01

Recent studies have suggested that undernutrition as defined using multidimensional nutritional evaluation tools may affect clinical outcomes in heart failure (HF). The evidence supporting this correlation is unclear. Therefore, we conducted this systematic review to critically appraise the use of multidimensional evaluation tools in the prediction of clinical outcomes in HF. We performed descriptive analyses of all identified articles involving qualitative analyses. We used STATA to conduct meta-analyses when at least three studies that tested the same type of nutritional assessment or screening tools and used the same outcome were identified. Sensitivity analyses were conducted to validate our positive results. We identified 17 articles with qualitative analyses and 11 with quantitative analysis after comprehensive literature searching and screening. We determined that the prevalence of malnutrition is high in HF (range 16-90 %), particularly in advanced and acute decompensated HF (approximate range 75-90 %). Undernutrition as identified by multidimensional evaluation tools may be significantly associated with hospitalization, length of stay and complications and is particularly strongly associated with high mortality. The meta-analysis revealed that compared with other tools, Mini Nutritional Assessment (MNA) scores were the strongest predictors of mortality in HF [HR (4.32, 95 % CI 2.30-8.11)]. Our results remained reliable after conducting sensitivity analyses. The prevalence of malnutrition is high in HF, particularly in advanced and acute decompensated HF. Moreover, undernutrition as identified by multidimensional evaluation tools is significantly associated with unfavourable prognoses and high mortality in HF.

Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies.

PubMed

Kuiper, Jisca S; Zuidersma, Marij; Zuidema, Sytse U; Burgerhof, Johannes Gm; Stolk, Ronald P; Oude Voshaar, Richard C; Smidt, Nynke

2016-08-01

Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families.

PubMed

Xu, X-H; Xiong, D-H; Liu, X-G; Guo, Y; Chen, Y; Zhao, J; Recker, R R; Deng, H-W

2010-01-01

This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of approximately 44% found in this study), but the relevant genetic study is still rather scarce. Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Significant associations with CSI were found with two SNPs (rs222029, P = 0.0019; rs222020, P = 0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males.

The association of air pollution and depressed mood in 70,928 individuals from four European cohorts.

PubMed

Zijlema, W L; Wolf, K; Emeny, R; Ladwig, K H; Peters, A; Kongsgård, H; Hveem, K; Kvaløy, K; Yli-Tuomi, T; Partonen, T; Lanki, T; Eeftens, M; de Hoogh, K; Brunekreef, B; Stolk, R P; Rosmalen, J G M

2016-03-01

Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 μg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 μg/m(3) increase in NO2). Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood. Copyright © 2015 Elsevier GmbH. All rights reserved.

Association of study quality with completeness of reporting: have completeness of reporting and quality of systematic reviews and meta-analyses in major radiology journals changed since publication of the PRISMA statement?

PubMed

Tunis, Adam S; McInnes, Matthew D F; Hanna, Ramez; Esmail, Kaisra

2013-11-01

To evaluate whether completeness of reporting of systematic reviews and meta-analyses in major radiology journals has changed since publication of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement; a secondary objective is to evaluate whether completeness of reporting (ie, PRISMA) is associated with study quality (ie, Assessing the Methodological Quality of Systematic Reviews [AMSTAR]). Systematic reviews and meta-analyses published in major radiology journals between January 2007 and December 2011 were identified by searching MEDLINE with the modified Montori method. Studies were reviewed independently by two investigators and assessed for adherence to the AMSTAR and PRISMA checklists. The average results were analyzed to assess for change in mean score before and after PRISMA publication and to assess results over time; a Pearson correlation coefficient was calculated to assess for any association between PRISMA and AMSTAR results. Included were 130 studies from 11 journals. Average PRISMA and AMSTAR results were 21.8 of 27 and 7.2 of 11, respectively. The average result was higher after publication of PRISMA, and PRISMA-reported items were 22.6 of 27 after publication of PRISMA versus 20.9 of 27 before publication of PRISMA; AMSTAR results were 7.7 of 11 after publication of PRISMA versus 6.7 of 11 before publication of PRISMA. There was a strong positive correlation (r = 0.86) between the PRISMA and AMSTAR results. There was high variability between journals. Radiology had the highest PRISMA reported items (24.7 of 27), and American Journal of Neuroradiology had the lowest (19.6 of 27). Two major areas for improvement include study protocol registration and assessment of risk of bias across studies (ie, publication bias). In major radiology journal studies, there was modest improvement in completeness of reporting of systematic reviews and meta-analyses, assessed by PRISMA, which was strongly associated with higher study quality, assessed by AMSTAR. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130273/-/DC1. RSNA, 2013

Deadlines at work and sleep quality. Cross-sectional and longitudinal findings among Danish knowledge workers.

PubMed

Rugulies, Reiner; Martin, Marie H T; Garde, Anne Helene; Persson, Roger; Albertsen, Karen

2012-03-01

Exposure to deadlines at work is increasing in several countries and may affect health. We aimed to investigate cross-sectional and longitudinal associations between frequency of difficult deadlines at work and sleep quality. Study participants were knowledge workers, drawn from a representative sample of Danish employees who responded to a baseline questionnaire in 2006 (n = 363) and a follow-up questionnaire in 2007 (n = 302). Frequency of difficult deadlines was measured by self-report and categorized into low, intermediate, and high. Sleep quality was measured with a Total Sleep Quality Score and two indexes (Awakening Index and Disturbed Sleep Index) derived from the Karolinska Sleep Questionnaire. Analyses on the association between frequency of deadlines and sleep quality scores were conducted with multiple linear regression models, adjusted for potential confounders. In addition, we used multiple logistic regression models to analyze whether frequency of deadlines at baseline predicted caseness of sleep problems at follow-up among participants free of sleep problems at baseline. Frequent deadlines were cross-sectionally and longitudinally associated with poorer sleep quality on all three sleep quality measures. Associations in the longitudinal analyses were greatly attenuated when we adjusted for baseline sleep quality. The logistic regression analyses showed that frequent deadlines at baseline were associated with elevated odds ratios for caseness of sleep problems at follow-up, however, confidence intervals were wide in these analyses. Frequent deadlines at work were associated with poorer sleep quality among Danish knowledge workers. We recommend investigating the relation between deadlines and health endpoints in large-scale epidemiologic studies. Copyright © 2011 Wiley Periodicals, Inc.

The interrelation between hypothyroidism and glaucoma: a critical review and meta-analyses.

PubMed

Thvilum, Marianne; Brandt, Frans; Brix, Thomas Heiberg; Hegedüs, Laszlo

2017-12-01

Data on the association between hypothyroidism and glaucoma are conflicting. We sought to shed light on this by conducting a critical review and meta-analyses. The meta-analyses were conducted in adherence with the widely accepted MOOSE guidelines. Using the Medical Subject Heading (MeSH) terms: hypothyroidism, myxoedema and glaucoma or intraocular pressure, case-control studies, cohort studies and cross-sectional studies were identified (PubMed) and reviewed. Using meta-analysis, the relative risk (RR) of coexistence of glaucoma and hypothyroidism was calculated. Based on the literature search, thirteen studies fulfilled the inclusion criteria and could be categorized into two groups based on the exposure. The designs of the studies varied considerably, and there was heterogeneity related to lack of power, weak phenotype classifications and length of follow-up. Eight studies had glaucoma (5757 patients) as exposure and hypothyroidism as outcome. Among these, we found a non-significantly increased risk of hypothyroidism associated with glaucoma (RR 1.65; 95% confidence interval [CI]: 0.97-2.82). Based on five studies (168 006 patients) with hypothyroidism as exposure and glaucoma as outcome, we found the risk of glaucoma to be significantly increased (RR 1.33; 95% CI: 1.13-1.58). Based on these meta-analyses, there seems to be an association between hypothyroidism and glaucoma, which does not seem to be the case between glaucoma and hypothyroidism. However, larger scale studies with better phenotype classification, longer follow-up and taking comorbidity and other biases into consideration are needed to address a potential causal relationship. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Red meat, diseases, and healthy alternatives: A critical review.

PubMed

Ekmekcioglu, Cem; Wallner, Peter; Kundi, Michael; Weisz, Ulli; Haas, Willi; Hutter, Hans-Peter

2018-01-22

Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B 12 . However, a high intake of red and processed meat is associated with an increased risk for diseases, especially type 2 diabetes and colorectal cancer, as several epidemiological studies and meta-analyses have shown. This review summarizes meta-analyses of publications studying the association between red and processed meat intake and type 2 diabetes, cardiovascular diseases, colorectal and other cancers, and all-cause mortality. Various potential mechanisms involved in the increased disease risk are discussed. Furthermore, the beneficial effects of healthy alternatives for meat, like fish, nuts, vegetables and fruits, pulses and legumes, whole grains, and dairy products are reviewed by including selected papers and recent meta-analyses.

Assessment of Alzheimer’s disease case–control associations using family-based methods

PubMed Central

Schjeide, Brit-Maren M.; McQueen, Matthew B.; Mullin, Kristina; DiVito, Jason; Hogan, Meghan F.; Parkinson, Michele; Hooli, Basavaraj; Lange, Christoph; Blacker, Deborah; Tanzi, Rudolph E.

2009-01-01

The genetics of Alzheimer’s disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case–control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes. PMID:18830724

Archival analyses of eyewitness identification test outcomes: what can they tell us about eyewitness memory?

PubMed

Horry, Ruth; Halford, Paul; Brewer, Neil; Milne, Rebecca; Bull, Ray

2014-02-01

Several archival studies of eyewitness identification have been conducted, but the results have been inconsistent and contradictory. We identify some avoidable pitfalls that have been present in previous analyses and present new data that address these pitfalls. We explored associations among various estimator variables and lineup outcomes for 833 "real life" lineups, including 588 lineups in which corroborating evidence of the suspect's guilt existed. Suspect identifications were associated with exposure duration, viewing distance, and the age of the witness. Nonidentifications were associated with the number of perpetrators. We also consider some of the inherent, unavoidable limitations with archival studies and consider what such studies can really tell researchers. We conclude that differences in sampling prohibit sensible comparisons between the results of laboratory and archival studies, and that the informational value of archival studies is actually rather limited.

CORRELATES OF RECOVERY FROM ALCOHOL DEPENDENCE: A PROSPECTIVE STUDY OVER A 3-YEAR FOLLOW-UP INTERVAL

PubMed Central

Dawson, Deborah A.; Goldstein, Risë B.; Ruan, W. June; Grant, Bridget F.

2011-01-01

Background Correlates of recovery from alcohol dependence have been identified through a variety of study designs characterized by different strengths and limitations. The goal of this study was to compare correlates of recovery based on a 3-year prospective design with those based on cross-sectional analyses of data from the same source. Methods Data from the 2001-2002 Wave 1 and 2004-2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to examine baseline characteristics associated with Wave 2 recovery from alcohol dependence, among those who classified with past-year DSM-IV alcohol dependence at Wave 1 (n=1,172). Results Abstinent recovery (AR) was significantly associated with Black/Asian/Hispanic race/ethnicity, children <1 year of age in the household at baseline, attending religious services ≥weekly at follow-up, and having initiated help seeking that comprised/included 12-step participation within <3 years prior to baseline. Nonabstinent recovery (NR) was positively associated with being never married at baseline, having job problems or being unemployed in the year preceding baseline, attending religious services

Has Adult Sleep Duration Declined Over the Last 50+ Years?

PubMed Central

Youngstedt, Shawn D.; Goff, Eric E.; Reynolds, Alex M.; Kripke, Daniel F.; Irwin, Michael R.; Bootzin, Richard R.; Khan, Nidha; Jean-Louis, Girardin

2015-01-01

Summary The common assumption that population sleep duration has declined in the past few decades has not been supported by recent reviews, which have been limited to self-reported data. The aim of this review was to assess whether there has been a reduction in objectively recorded sleep duration over the last 50+ years. The literature was searched for studies published from 1960–2013, which assessed objective sleep duration (TST) in healthy normal-sleeping adults. The search found 168 studies that met inclusion criteria, with 257 data points representing 6,052 individuals ages 18–88 years. Data were assessed by comparing the regression lines of age vs. TST in studies conducted between 1960–1989 vs. 1990–2013. Weighted regression analyses assessed the association of year of study with age-adjusted TST across all data points. Regression analyses also assessed the association of year of study with TST separately for 10-year age categories (e.g., ages 18–27 years), and separately for polysomnographic and actigraphic data, and for studies involving a fixed sleep schedule and participants’ customary sleep schedules. Analyses revealed no significant association of sleep duration with study year. The results are consistent with recent reviews of subjective data, which have challenged the notion of a modern epidemic of insufficient sleep. PMID:26478985

Association of Genetic Risk for Schizophrenia With Nonparticipation Over Time in a Population-Based Cohort Study.

PubMed

Martin, Joanna; Tilling, Kate; Hubbard, Leon; Stergiakouli, Evie; Thapar, Anita; Davey Smith, George; O'Donovan, Michael C; Zammit, Stanley

2016-06-15

Progress has recently been made in understanding the genetic basis of schizophrenia and other psychiatric disorders. Longitudinal studies are complicated by participant dropout, which could be related to the presence of psychiatric problems and associated genetic risk. We tested whether common genetic variants implicated in schizophrenia were associated with study nonparticipation among 7,867 children and 7,850 mothers from the Avon Longitudinal Study of Parents and Children (ALSPAC; 1991-2007), a longitudinal population cohort study. Higher polygenic risk scores for schizophrenia were consistently associated with noncompletion of questionnaires by study mothers and children and nonattendance at data collection throughout childhood and adolescence (ages 1-15 years). These associations persisted after adjustment for other potential correlates of nonparticipation. Results suggest that persons at higher genetic risk for schizophrenia are likely to be underrepresented in cohort studies, which will underestimate risk of this and related psychiatric, cognitive, and behavioral phenotypes in the population. Statistical power to detect associations with these phenotypes will be reduced, while analyses of schizophrenia-related phenotypes as outcomes may be biased by the nonrandom missingness of these phenotypes, even if multiple imputation is used. Similarly, in complete-case analyses, collider bias may affect associations between genetic risk and other factors associated with missingness. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Association between environmental factors including second-hand smoke and primary lung cancer in dogs.

PubMed

Zierenberg-Ripoll, A; Pollard, R E; Stewart, S L; Allstadt, S D; Barrett, L E; Gillem, J M; Skorupski, K A

2018-06-01

To estimate prevalence of exposure to environmental tobacco smoke and other environmental toxins in dogs with primary lung tumours and to analyse association between exposure and lung tumour development. In this case-control study, an owner survey was developed to collect data on patient characteristics, general health care and environmental exposures. Dogs diagnosed with primary lung carcinomas formed the Case group. Dogs diagnosed with mast cell tumours served as Control Group 1 and dogs diagnosed with neurologic disease served as Control Group 2. Associations between diagnosis of primary lung tumour and patient and environmental exposure variables were analysed using bivariate and multivariate statistical methods. A total of 1178 owner surveys were mailed and 470 surveys were returned and included in statistical analysis, including 135 Cases, 169 dogs in Control Group 1 and 166 dogs in Control Group 2. An association between exposure to second-hand smoke and prevalence of primary lung cancer was not identified in this study. Second-hand smoke is associated with primary lung cancer in people but a definitive association has not been found in dogs. The results of this study suggest that tobacco smoke exposure may not be associated with primary lung cancer development in dogs but study limitations may have precluded detection of an association. © 2017 British Small Animal Veterinary Association.

Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses.

PubMed

Qiu, Ying-Hua; Deng, Fei-Yan; Tang, Zai-Xiang; Jiang, Zhen-Huan; Lei, Shu-Feng

2015-10-01

Type 1 diabetes mellitus (type 1 DM) is an autoimmune disease. Although genome-wide association studies (GWAS) and meta-analyses have successfully identified numerous type 1 DM-associated susceptibility loci, the underlying mechanisms for these susceptibility loci are currently largely unclear. Based on publicly available datasets, we performed integrative analyses (i.e., integrated gene relationships among implicated loci, differential gene expression analysis, functional prediction and functional annotation clustering analysis) and combined with expression quantitative trait loci (eQTL) results to further explore function mechanisms underlying the associations between genetic variants and type 1 DM. Among a total of 183 type 1 DM-associated SNPs, eQTL analysis showed that 17 SNPs with cis-regulated eQTL effects on 9 genes. All the 9 eQTL genes enrich in immune-related pathways or Gene Ontology (GO) terms. Functional prediction analysis identified 5 SNPs located in transcription factor (TF) binding sites. Of the 9 eQTL genes, 6 (TAP2, HLA-DOB, HLA-DQB1, HLA-DQA1, HLA-DRB5 and CTSH) were differentially expressed in type 1 DM-associated related cells. Especially, rs3825932 in CTSH has integrative functional evidence supporting the association with type 1 DM. These findings indicated that integrative analyses can yield important functional information to link genetic variants and type 1 DM. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

77 FR 23515 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... from a quantitative, comprehensive or even representative survey or study of the burdens associated... existing registered money market fund: Documentation of credit risk analyses, and determinations regarding... for documentation of credit analyses and other determinations) = 2340 responses. (30 funds x 12...

Cross-sectional study on risk factors of HIV among female commercial sex workers in Cambodia.

PubMed Central

Ohshige, K.; Morio, S.; Mizushima, S.; Kitamura, K.; Tajima, K.; Ito, A.; Suyama, A.; Usuku, S.; Saphonn, V.; Heng, S.; Hor, L. B.; Tia, P.; Soda, K.

2000-01-01

To describe epidemiological features on HIV prevalence among female commercial sex workers (CSWs), a cross-sectional study on sexual behaviour and serological prevalence was carried out in Cambodia. The CSWs were interviewed on their demographic characters and behaviour and their blood samples were taken for testing on sexually transmitted diseases, including HIV, Chlamydia trachomatis, syphilis, and hepatitis B. Associations between risk factors and HIV seropositivity were analysed. High seroprevalence of HIV and Chlamydia trachomatis IgG antibody (CT-IgG-Ab) was shown among the CSWs (54 and 81.7%, respectively). Univariate logistic regression analyses showed an association between HIV seropositivity and age, duration of prostitution, the number of clients per day and CT-IgG-Ab. Especially, high-titre chlamydial seropositivity showed a strong significant association with HIV prevalence. In multiple logistic regression analyses, CT-IgG-Ab with higher titre was significantly independently related to HIV infection. These suggest that existence of Chlamydia trachomatis is highly related to HIV prevalence. PMID:10722142

The role of renin-angiotensin-aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Kelly, Tanika N; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R; Ricardo, Ana C; Rosas, Sylvia E; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang

2015-10-01

We conducted single-marker, gene- and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m(2)/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P < 1.00 × 10(-6)). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P < 1.00 × 10(-6)). No single-marker associations with CKD progression were observed. The current study provides strong evidence for a role of the RAAS in CKD progression. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The role of renin–angiotensin–aldosterone system genes in the progression of chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study

PubMed Central

Kelly, Tanika N.; Raj, Dominic; Rahman, Mahboob; Kretzler, Matthias; Kallem, Radhakrishna R.; Ricardo, Ana C.; Rosas, Sylvia E.; Tao, Kaixiang; Xie, Dawei; Hamm, Lotuce Lee; He, Jiang; Appel, J.; Feldman, Harold I.; Go, Alan S.; Kusek, John W.; Lash, James P.; Ojo, Akinlolu; Townsend, Raymond R.

2015-01-01

Background We conducted single-marker, gene- and pathway-based analyses to examine the association between renin–angiotensin–aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort study participants. Methods A total of 1523 white and 1490 black subjects were genotyped for 490 single nucleotide polymorphisms (SNPs) in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end-stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene- and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing. Results Among white and black participants, eGFR declined an average of 1.2 and 2.3 mL/min/1.73 m2/year, respectively, while renal events occurred in a respective 11.5 and 24.9% of participants. We identified strong gene- and pathway-based associations with CKD progression. The AGT and RENBP genes were consistently associated with risk of renal events in separate analyses of white and black participants (both P < 1.00 × 10−6). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both P < 1.00 × 10−6). No single-marker associations with CKD progression were observed. Conclusions The current study provides strong evidence for a role of the RAAS in CKD progression. PMID:25906781

Does shared family background influence the impact of educational differences on early mortality?

PubMed

Søndergaard, Grethe; Mortensen, Laust H; Nybo Andersen, Anne-Marie; Andersen, Per Kragh; Dalton, Susanne Oksbjerg; Madsen, Mia; Osler, Merete

2012-10-15

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009. The authors used Cox regression analyses to estimate hazard ratios for mortality according to educational level. Conventional cohort and intersibling analyses were carried out and conducted separately for deaths occurring before and after the age of 45 years, respectively. The cohort analyses showed an inverse association between educational status and all-cause mortality that was strongest for males, increased with younger birth cohorts, and tended to be strongest in the analyses of death before 45 years of age. The associations were attenuated slightly in the intersibling analyses and after adjustment for serious health conditions in early life. Hence, health selection and confounding by factors shared by siblings explained only a minor part of the association between educational level and all-cause mortality.

Memory management in genome-wide association studies

PubMed Central

2009-01-01

Genome-wide association is a powerful tool for the identification of genes that underlie common diseases. Genome-wide association studies generate billions of genotypes and pose significant computational challenges for most users including limited computer memory. We applied a recently developed memory management tool to two analyses of North American Rheumatoid Arthritis Consortium studies and measured the performance in terms of central processing unit and memory usage. We conclude that our memory management approach is simple, efficient, and effective for genome-wide association studies. PMID:20018047

A systematic review of the association between family meals and adolescent risk outcomes.

PubMed

Goldfarb, Samantha S; Tarver, Will L; Locher, Julie L; Preskitt, Julie; Sen, Bisakha

2015-10-01

To conduct a systematic review of the literature examining the relationship between family meals and adolescent health risk outcomes. We performed a systematic search of original empirical studies published between January 1990 and September 2013. Based on data from selected studies, we conducted logistic regression models to examine the correlates of reporting a protective association between frequent family meals and adolescent outcomes. Of the 254 analyses from 26 selected studies, most reported a significant association between family meals and the adolescent risk outcome-of-interest. However, model analyses which controlled for family connectedness variables, or used advanced empirical methods to account for family-level confounders, were less likely than unadjusted models to report significant relationships. The type of analysis conducted was significantly associated with the likelihood of finding a protective relationship between family meals and the adolescent outcome-of-interest, yet very few studies are using such methods in the literature. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation.

PubMed

Xia, Charley; Amador, Carmen; Huffman, Jennifer; Trochet, Holly; Campbell, Archie; Porteous, David; Hastie, Nicholas D; Hayward, Caroline; Vitart, Veronique; Navarro, Pau; Haley, Chris S

2016-02-01

Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors.

Is gender inequality in the domestic sphere associated with psychological distress among women and men? Results from the Northern Swedish Cohort.

PubMed

Harryson, Lisa; Novo, Mehmed; Hammarström, Anne

2012-03-01

The aim of this study was to analyse whether gender inequality in the domestic sphere was associated with psychological distress among women and men. In a cohort study, all pupils in the last year of compulsory school in a middle-sized industrial town in northern Sweden were followed until the age of 42. For this study a sample of cohabiting participants (n=372 women, 352 men) was selected. Gender inequality was measured as perceptions of gender inequality in the couple relationship, time spent on household work, responsibility for domestic work and childcare, and was analysed in relation to psychological distress, after taking possible background variables as well as earlier health status into account. In the multivariate analyses, perception of gender inequality in the couple relationship was associated with psychological distress for both women (OR 2.23, CI 1.20 to 4.18) and men (OR 3.51, CI 1.69 to 7.31). For women only, taking whole responsibility for domestic work was associated with the outcome (OR 2.17, CI 1.05 to 4.48). For men, taking less than half of the responsibility for domestic work was associated with psychological distress (OR 2.25, CI 1.24 to 3.91). Gender inequality in the domestic sphere seems to be an important determinant of psychological distress for both women and men.

Association between sleep difficulties as well as duration and hypertension: is BMI a mediator?

PubMed

Carrillo-Larco, R M; Bernabe-Ortiz, A; Sacksteder, K A; Diez-Canseco, F; Cárdenas, M K; Gilman, R H; Miranda, J J

2017-01-01

Sleep difficulties and short sleep duration have been associated with hypertension. Though body mass index (BMI) may be a mediator variable, the mediation effect has not been defined. We aimed to assess the association between sleep duration and sleep difficulties with hypertension, to determine if BMI is a mediator variable, and to quantify the mediation effect. We conducted a mediation analysis and calculated prevalence ratios with 95% confidence intervals. The exposure variables were sleep duration and sleep difficulties, and the outcome was hypertension. Sleep difficulties were statistically significantly associated with a 43% higher prevalence of hypertension in multivariable analyses; results were not statistically significant for sleep duration. In these analyses, and in sex-specific subgroup analyses, we found no strong evidence that BMI mediated the association between sleep indices and risk of hypertension. Our findings suggest that BMI does not appear to mediate the association between sleep patterns and hypertension. These results highlight the need to further study the mechanisms underlying the relationship between sleep patterns and cardiovascular risk factors.

Gender inequalities in mental wellbeing in 26 European countries: do welfare regimes matter?

PubMed

Dreger, Stefanie; Gerlinger, Thomas; Bolte, Gabriele

2016-10-01

Nature and extent of welfare regimes and social policies are important determinants of health and health inequalities. This study examines the association of gender and mental wellbeing in European countries and investigates whether type of welfare regime plays a role in this association. Data of 19 366 women and 14 338 men of the third round of the European Quality of Life Survey (2011-12) was used to analyse mental wellbeing, assessed by the World Health Organization 5-Mental Wellbeing Index. Multilevel logistic regression analyses were performed to analyse the association between gender and good mental wellbeing first at country-level, and secondly the between country variation was analysed and welfare regimes were included as explanatory variables. We observed cross-national variation in good mental wellbeing. At country levels gender inequalities in good mental wellbeing were observed in 7 out of 26 countries. In analyses considering all countries together gender inequalities in good mental wellbeing were identified independent of further individual socio-demographic variables and independent of the welfare regimes that people lived in [women vs. men: OR = 0.76; (95% CI = 0.71-0.81)]. Gender inequalities in good mental wellbeing were not modified by welfare regimes. There are cross-national differences in good mental wellbeing between European countries. Gender inequalities with a lower prevalence of good mental wellbeing among women are common in European countries. This study suggests that welfare regimes do not modify these gender inequalities in mental wellbeing. © The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Predictors of cancer fear: the association between mass media and fear of cancer among cancer diagnosed and nondiagnosed individuals.

PubMed

Nelissen, Sara; Beullens, Kathleen; Lemal, Marijke; Van den Bulck, Jan

2015-03-01

Few studies have explored the impact of mass media on fear of cancer levels. This study investigates whether television and Internet use are associated with fear of cancer, and whether this association is different for cancer diagnosed and nondiagnosed individuals. A quantitative, standardized survey was used and administered to 2008 respondents in Flanders (Belgium), of which 621 individuals were diagnosed with cancer. For statistical analyses, hierarchical regression analyses, independent samples T-tests and post hoc mediation analyses were conducted. The results indicated that cancer diagnosed individuals differed from nondiagnosed individuals in terms of perceived cancer susceptibility, perceived cancer severity, fear of cancer, and media use. Furthermore, television exposure was directly and positively related to fear of cancer, whereas Internet use was not. The relationship between television and Internet use and fear of cancer was not different for cancer diagnosed and nondiagnosed individuals. Additional post hoc mediation analyses, however, seemed to suggest that watching more television and surfing more on the Internet could both lead to having a more negative perceived health and this was in turn associated with higher fear of cancer. To help reduce the burden of fear of cancer, cancer educators and individuals working with cancer patients need to be aware of the possible negative effects media use might have on health perception and on the levels of fear of cancer.

Gene-set and multivariate genome-wide association analysis of oppositional defiant behavior subtypes in attention-deficit/hyperactivity disorder.

PubMed

Aebi, Marcel; van Donkelaar, Marjolein M J; Poelmans, Geert; Buitelaar, Jan K; Sonuga-Barke, Edmund J S; Stringaris, Argyris; Consortium, Image; Faraone, Stephen V; Franke, Barbara; Steinhausen, Hans-Christoph; van Hulzen, Kimm J E

2016-07-01

Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Gene‐set and multivariate genome‐wide association analysis of oppositional defiant behavior subtypes in attention‐deficit/hyperactivity disorder

PubMed Central

van Donkelaar, Marjolein M. J.; Poelmans, Geert; Buitelaar, Jan K.; Sonuga‐Barke, Edmund J. S.; Stringaris, Argyris; consortium, IMAGE; Faraone, Stephen V.; Franke, Barbara; Steinhausen, Hans‐Christoph; van Hulzen, Kimm J. E.

2015-01-01

Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention‐deficit‐hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5‐HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome‐wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for “parental ability to cope with disruptive behavior.” None of the hypothesis‐driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome‐wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top‐ranked genes functionally interact in a molecular landscape centered around Beta‐catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. © 2015 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:26184070

Association between adolescent marriage and intimate partner violence: a study of young adult women in Bangladesh.

PubMed

Rahman, Mosfequr; Hoque, Md Aminul; Mostofa, Md Golam; Makinoda, Satoru

2014-03-01

This study explores the association between adolescent marriage and intimate partner violence (IPV) among young adult women using 2007 Bangladesh Demographic Health Survey data. The analyses are restricted to young women 20 to 24 years old. Logistic regression analyses are constructed to estimate the odds ratios and 95% confidence intervals for the association between adolescent marriage and IPV in the past year. show that there is a strong significant relationship between adolescent marriage and experience of physical IPV in the past year among this population. Association between sexual IPV and adolescent marriage is insignificant. Adolescent marriage puts women at increased risk of physical IPV into their young adult period. Government agencies need to enforce existing law on the minimum age at marriage to reduce IPV among adolescent and young adult girls.

A population-based study of associations between current posttraumatic stress symptoms and current fatigue.

PubMed

Lerdal, Anners; Lee, Kathryn A; Rokne, Berit; Knudsen, Øistein; Wahl, Astrid K; Dahl, Alv A

2010-10-01

This study explores current experience with posttraumatic stress disorder (PTSD) symptoms and other variables (sociodemographic, mental distress, somatic morbidity, self-rated health, and quality of life [QoL]) in relation to fatigue. A representative sample of the Norwegian population (N = 3,944) was invited to participate in a mailed survey, and 1,857 (47%) returned valid responses on the questionnaire that included the Fatigue Severity Scale and the Posttraumatic Symptom Scale-10. Posttraumatic stress disorder symptoms showed a strong association with fatigue in univariate (β = .41) and multivariate analyses (β = .33). Associations between psychosocial health variables, QoL, and fatigue were confirmed. However, PTSD symptoms showed the strongest association with fatigue in the analyses. Findings need to be replicated in other population samples and in clinical samples with PTSD and fatigue.

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.

Food Polyamine and Cardiovascular Disease -An Epidemiological Study-

PubMed Central

Soda, Kuniyasu; Kano, Yoshihiko; Chiba, Fumihiro

2012-01-01

The purpose of this study was to examine the contribution of dietary polyamines toward preventing cardiovascular disease (CVD). Age-standardized mortality rates as well as other relevant information regarding individuals with CVD were gathered from the World Health Organization and the International Monetary Fund in 48 different European and other Western countries. Food supply data were collected from the database of the United Nations, and the amount of dietary polyamines was estimated by using polyamine concentrations in foods from published sources. The association between CVD mortality and the amount of polyamines was investigated by performing a series of multiple linear regression analyses. Analyses using factors known to modulate the risk of CVD including: Gross Domestic Product (GDP) (standardized regression coefficient (r) = -0.786, p < 0.001) and the amount of fruits, vegetable, nuts, and beans (r = -0.183, p = 0.001) but not including polyamines, showed negative associations with CVD, while smoking rate (r = 0.139, p = 0.041) and whole milk amount (r = 0.131, p = 0.028) showed positive associations with CVD. When the amount of polyamines was added to the analyses as a covariate, GDP (r = -0.864, p < 0.001) and polyamines (r = -0.355, p = 0.007) showed negative associations with CVD, while smoking rate (r = 0.183, p = 0.006) and whole milk (r = 0.113, p = 0.041) showed positive associations with CVD. The inverse association between dietary polyamines and CVD mortality revealed by the present study merits further evaluation. PMID:23121753

Food polyamine and cardiovascular disease--an epidemiological study.

PubMed

Soda, Kuniyasu; Kano, Yoshihiko; Chiba, Fumihiro

2012-09-28

The purpose of this study was to examine the contribution of dietary polyamines toward preventing cardiovascular disease (CVD). Age-standardized mortality rates as well as other relevant information regarding individuals with CVD were gathered from the World Health Organization and the International Monetary Fund in 48 different European and other Western countries. Food supply data were collected from the database of the United Nations, and the amount of dietary polyamines was estimated by using polyamine concentrations in foods from published sources. The association between CVD mortality and the amount of polyamines was investigated by performing a series of multiple linear regression analyses. Analyses using factors known to modulate the risk of CVD including: Gross Domestic Product (GDP) (standardized regression coefficient (r) = -0.786, p < 0.001) and the amount of fruits, vegetable, nuts, and beans (r = -0.183, p = 0.001) but not including polyamines, showed negative associations with CVD, while smoking rate (r = 0.139, p = 0.041) and whole milk amount (r = 0.131, p = 0.028) showed positive associations with CVD. When the amount of polyamines was added to the analyses as a covariate, GDP (r = -0.864, p < 0.001) and polyamines (r = -0.355, p = 0.007) showed negative associations with CVD, while smoking rate (r = 0.183, p = 0.006) and whole milk (r = 0.113, p = 0.041) showed positive associations with CVD. The inverse association between dietary polyamines and CVD mortality revealed by the present study merits further evaluation.

Is somatic comorbidity associated with more somatic symptoms, mental distress, or unhealthy lifestyle in elderly cancer survivors?

PubMed

Grov, Ellen Karine; Fosså, Sophie D; Dahl, Alv A

2009-06-01

The associations of lifestyle factors, somatic symptoms, mental distress, and somatic comorbidity in elderly cancer survivors have not been well studied. This study examines these associations among elderly cancer survivors (age >or=65 years) in a population-based sample. A cross-sectional comparative study of Norwegian elderly cancer survivors. Combining information from The Norwegian Cancer Registry, and by self-reporting, 972 elderly cancer survivors were identified, of whom 632 (65%) had somatic comorbidity and 340 did not. Elderly cancer survivors with somatic comorbidity had significantly higher BMI, more performed minimal physical activity, had more somatic symptoms, used more medication, and had more frequently seen a medical doctor than survivors without somatic comorbidity. In multivariable analyses, unhealthy lifestyle and higher somatic symptoms scores were significantly associated with cancer cases with somatic comorbidity. In univariate analyses those with somatic comorbidity were significantly older, had lower levels of education, higher proportions of BMI >or= 30, less physical activity, poorer self-rated health, higher somatic symptoms score, more mental distress, had more frequently seen a medical doctor last year, and more frequently used daily medication. Our outcome measures of lifestyle, somatic symptoms and mental distress were all significantly associated with somatic comorbidity in elderly cancer survivors, however only lifestyle and somatic symptoms were significant in multivariable analyses. In elderly cancer survivors not only cancer, but also somatic comorbidity, deserve attention. Such comorbidity is associated with unhealthy lifestyles, more somatic symptoms and mental distress which should be evaluated and eventually treated.

Vestibular vertigo is associated with abnormal sleep duration.

PubMed

Albathi, Monirah; Agrawal, Yuri

2017-01-01

Several small studies in animals and humans have suggested a relationship between vestibular function and sleep. In this study, we evaluate the association between vestibular vertigo and sleep duration in a large, representative sample of US adults. We used data from the National Health Interview Survey, which administered a Balance Supplement in 2008 in a sample of 20,950 adult respondents. We evaluated the cross-sectional association between vestibular vertigo (based on a well-validated definition) and sleep duration (defined as short <6 hours, normal 6-8 hours, and long >8 hours). We performed multiple and multinomial logistic regression analyses to estimate the odds ratio and relative risk ratio (RRR) of impaired sleep duration compared to normal sleep duration associated with vestibular vertigo. Analyses were adjusted for demographic, lifestyle and health behavior characteristics as well as relevant comorbid conditions. Thirty percent of individuals with vestibular vertigo reported abnormal sleep duration (15.5% short duration and 14.8% long duration). In adjusted analyses, individuals with vestibular vertigo had a 1.75 (95% CI 1.45-2.11) RRR of having short sleep duration compared to individuals without vestibular vertigo, and a 1.55 (95% CI 1.26-1.91) RRR of having long sleep duration compared to individuals without vestibular vertigo. This study presents epidemiologic evidence to support the association between vestibular function and sleep duration. Individuals with vestibular vertigo had a higher RRR for abnormally short or long sleep duration. Further work is needed to evaluate the causal direction(s) of this association.

What is the optimal rate of caesarean section at population level? A systematic review of ecologic studies.

PubMed

Betran, Ana Pilar; Torloni, Maria Regina; Zhang, Jun; Ye, Jiangfeng; Mikolajczyk, Rafael; Deneux-Tharaux, Catherine; Oladapo, Olufemi Taiwo; Souza, João Paulo; Tunçalp, Özge; Vogel, Joshua Peter; Gülmezoglu, Ahmet Metin

2015-06-21

In 1985, WHO stated that there was no justification for caesarean section (CS) rates higher than 10-15% at population-level. While the CS rates worldwide have continued to increase in an unprecedented manner over the subsequent three decades, concern has been raised about the validity of the 1985 landmark statement. We conducted a systematic review to identify, critically appraise and synthesize the analyses of the ecologic association between CS rates and maternal, neonatal and infant outcomes. Four electronic databases were searched for ecologic studies published between 2000 and 2014 that analysed the possible association between CS rates and maternal, neonatal or infant mortality or morbidity. Two reviewers performed study selection, data extraction and quality assessment independently. We identified 11,832 unique citations and eight studies were included in the review. Seven studies correlated CS rates with maternal mortality, five with neonatal mortality, four with infant mortality, two with LBW and one with stillbirths. Except for one, all studies were cross-sectional in design and five were global analyses of national-level CS rates versus mortality outcomes. Although the overall quality of the studies was acceptable; only two studies controlled for socio-economic factors and none controlled for clinical or demographic characteristics of the population. In unadjusted analyses, authors found a strong inverse relationship between CS rates and the mortality outcomes so that maternal, neonatal and infant mortality decrease as CS rates increase up to a certain threshold. In the eight studies included in this review, this threshold was at CS rates between 9 and 16%. However, in the two studies that adjusted for socio-economic factors, this relationship was either weakened or disappeared after controlling for these confounders. CS rates above the threshold of 9-16% were not associated with decreases in mortality outcomes regardless of adjustments. Our findings could be interpreted to mean that at CS rates below this threshold, socio-economic development may be driving the ecologic association between CS rates and mortality. On the other hand, at rates higher than this threshold, there is no association between CS and mortality outcomes regardless of adjustment. The ecological association between CS rates and relevant morbidity outcomes needs to be evaluated before drawing more definite conclusions at population level.

Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults

PubMed Central

Reijman, Sophie; Bakermans-Kranenburg, Marian J.; Hiraoka, Regina; Crouch, Julie L.; Milner, Joel S.; van IJzendoorn, Marinus H.

2016-01-01

We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner’s curse. Most studies were underpowered. Future directions for research are suggested. PMID:27462035

Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder

PubMed Central

Amare, Azmeraw T.; Schubert, Klaus Oliver; Tekola-Ayele, Fasil; Hsu, Yi-Hsiang; Sangkuhl, Katrin; Jenkins, Gregory; Whaley, Ryan M.; Barman, Poulami; Batzler, Anthony; Altman, Russ B.; Arolt, Volker; Brockmöller, Jürgen; Chen, Chia-Hui; Domschke, Katharina; Hall-Flavin, Daniel K.; Hong, Chen-Jee; Illi, Ari; Ji, Yuan; Kampman, Olli; Kinoshita, Toshihiko; Leinonen, Esa; Liou, Ying-Jay; Mushiroda, Taisei; Nonen, Shinpei; Skime, Michelle K.; Wang, Liewei; Kato, Masaki; Liu, Yu-Li; Praphanphoj, Verayuth; Stingl, Julia C.; Bobo, William V.; Tsai, Shih-Jen; Kubo, Michiaki; Klein, Teri E.; Weinshilboum, Richard M.; Biernacka, Joanna M.; Baune, Bernhard T.

2018-01-01

Studies reported a strong genetic correlation between the Big Five personality traits and major depressive disorder (MDD). Moreover, personality traits are thought to be associated with response to antidepressants treatment that might partly be mediated by genetic factors. In this study, we examined whether polygenic scores (PGSs) derived from the Big Five personality traits predict treatment response and remission in patients with MDD who were prescribed selective serotonin reuptake inhibitors (SSRIs). In addition, we performed meta-analyses of genome-wide association studies (GWASs) on these traits to identify genetic variants underpinning the cross-trait polygenic association. The PGS analysis was performed using data from two cohorts: the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS, n = 529) and the International SSRI Pharmacogenomics Consortium (ISPC, n = 865). The cross-trait GWAS meta-analyses were conducted by combining GWAS summary statistics on SSRIs treatment outcome and on the personality traits. The results showed that the PGS for openness and neuroticism were associated with SSRIs treatment outcomes at p < 0.05 across PT thresholds in both cohorts. A significant association was also found between the PGS for conscientiousness and SSRIs treatment response in the PGRN-AMPS sample. In the cross-trait GWAS meta-analyses, we identified eight loci associated with (a) SSRIs response and conscientiousness near YEATS4 gene and (b) SSRI remission and neuroticism eight loci near PRAG1, MSRA, XKR6, ELAVL2, PLXNC1, PLEKHM1, and BRUNOL4 genes. An assessment of a polygenic load for personality traits may assist in conjunction with clinical data to predict whether MDD patients might respond favorably to SSRIs. PMID:29559929

Plasma amyloid β, depression, and dementia in community-dwelling elderly.

PubMed

Direk, Nese; Schrijvers, Elisabeth M C; de Bruijn, Renée F A G; Mirza, Saira; Hofman, Albert; Ikram, M Arfan; Tiemeier, Henning

2013-04-01

Plasma amyloid β (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, a few clinical studies tested the cross-sectional association of Aβ levels with depression in elderly and showed incongruous findings. Hence, we tested the longitudinal association between Aβ levels and depressive symptoms in community-dwelling elderly. The study is embedded in a population-based cohort of 980 participants aged 60 years or older from the Rotterdam Study with Aβ levels. Participants were evaluated for depressive symptoms with the Centre for Epidemiological Studies-Depression scale at baseline and repeatedly over the mean follow-up of 11 years. We first performed cross-sectional analyses. Then, we tested the longitudinal association between Aβ levels and depressive symptoms after excluding participants with dementia during follow-up. In cross-sectional analyses, persons with high Aβ(1-40) levels had more clinically relevant depressive symptoms. However, this association was accounted for by persons with clinically relevant depressive symptoms who developed dementia within the next 11 years. In longitudinal analyses, persons with low levels of Aβ(1-40) and Aβ(1-42) without dementia had a higher risk of clinically relevant depressive symptoms during the follow-up. These findings suggest that the cross-sectional association between high plasma Aβ levels and clinically relevant depressive symptoms in the elderly is due to prodromal dementia. In contrast, the longitudinal association between low plasma Aβ levels and depressive symptoms could not be explained by dementia during follow-up suggesting that Aβ peptides may play a distinct role on depression etiology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genome Wide Association Study of Sepsis in Extremely Premature Infants

PubMed Central

Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh; Murray, Jeffrey C.; Das, Abhik; Higgins, Rosemary D.; Carlo, Waldemar A.; Bell, Edward F.; Goldberg, Ronald N.; Schibler, Kurt; Sood, Beena G.; Stevenson, David K.; Stoll, Barbara J.; Van Meurs, Krisa P.; Johnson, Karen J.; Levy, Joshua; McDonald, Scott A.; Zaterka-Baxter, Kristin M.; Kennedy, Kathleen A.; Sánchez, Pablo J.; Duara, Shahnaz; Walsh, Michele C.; Shankaran, Seetha; Wynn, James L.; Cotten, C. Michael

2017-01-01

Objective To identify genetic variants associated with sepsis (early and late-onset) using a genome wide association (GWA) analysis in a cohort of extremely premature infants. Study Design Previously generated GWA data from the Neonatal Research Network’s anonymized genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole genome amplified DNA was genotyped for 1.2 million single nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. P values and false discovery rates were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10−5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points. Results Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10−8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram positive sepsis), RALA, IMMP2L (Gram negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and Interleukin-1 associated receptor kinase 2 (p values<0.001 and FDR<20%). Conclusions No SNPs met genome-wide significance in this cohort of ELBW infants; however, areas of potential association and pathways meriting further study were identified. PMID:28283553

Discovery of novel heart rate-associated loci using the Exome Chip

PubMed Central

van den Berg, Marten E.; Warren, Helen R.; Cabrera, Claudia P.; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A.; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J.; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A.; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V.; Lyytikäinen, Leo-Pekka; Hall, Leanne M.; van Setten, Jessica; Trompet, Stella; Prins, Bram P.; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A.; Silva, Claudia T.; Alonso, Alvaro; Bis, Joshua C.; de Boer, Rudolf; de Haan, Hugoline G.; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F.; Doney, Alex S. F.; Ellinor, Patrick T.; Eppinga, Ruben N.; Felix, Stephan B.; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B.; Heckbert, Susan R.; Huang, Paul L.; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K.; Kolcic, Ivana; Launer, Lenore J.; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W.; Mangino, Massimo; Morris, Andrew D.; Mulas, Antonella; Murray, Alison D.; Nelson, Christopher P.; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J.; Poulter, Neil; Psaty, Bruce M.; Qi, Lihong; Raitakari, Olli T.; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F.; Soliman, Elsayed Z.; Spector, Timothy D.; Stanton, Alice V.; Stirrups, Kathleen E.; Taylor, Kent D.; Tobin, Martin D.; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W.; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M.; Zeggini, Eleftheria; Jukema, J. Wouter; Asselbergs, Folkert W.; Samani, Nilesh J.; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A.; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J.; Palmer, Colin N. A.; Sanna, Serena; Mook-Kanamori, Dennis O.; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I.; Dörr, Marcus; O'Donnell, Chris J.; Hayward, Caroline; Arking, Dan E.; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H.; Munroe, Patricia B.

2017-01-01

Abstract Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods. We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants. Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. PMID:28379579

Discovery of novel heart rate-associated loci using the Exome Chip.

PubMed

van den Berg, Marten E; Warren, Helen R; Cabrera, Claudia P; Verweij, Niek; Mifsud, Borbala; Haessler, Jeffrey; Bihlmeyer, Nathan A; Fu, Yi-Ping; Weiss, Stefan; Lin, Henry J; Grarup, Niels; Li-Gao, Ruifang; Pistis, Giorgio; Shah, Nabi; Brody, Jennifer A; Müller-Nurasyid, Martina; Lin, Honghuang; Mei, Hao; Smith, Albert V; Lyytikäinen, Leo-Pekka; Hall, Leanne M; van Setten, Jessica; Trompet, Stella; Prins, Bram P; Isaacs, Aaron; Radmanesh, Farid; Marten, Jonathan; Entwistle, Aiman; Kors, Jan A; Silva, Claudia T; Alonso, Alvaro; Bis, Joshua C; de Boer, Rudolf; de Haan, Hugoline G; de Mutsert, Renée; Dedoussis, George; Dominiczak, Anna F; Doney, Alex S F; Ellinor, Patrick T; Eppinga, Ruben N; Felix, Stephan B; Guo, Xiuqing; Hagemeijer, Yanick; Hansen, Torben; Harris, Tamara B; Heckbert, Susan R; Huang, Paul L; Hwang, Shih-Jen; Kähönen, Mika; Kanters, Jørgen K; Kolcic, Ivana; Launer, Lenore J; Li, Man; Yao, Jie; Linneberg, Allan; Liu, Simin; Macfarlane, Peter W; Mangino, Massimo; Morris, Andrew D; Mulas, Antonella; Murray, Alison D; Nelson, Christopher P; Orrú, Marco; Padmanabhan, Sandosh; Peters, Annette; Porteous, David J; Poulter, Neil; Psaty, Bruce M; Qi, Lihong; Raitakari, Olli T; Rivadeneira, Fernando; Roselli, Carolina; Rudan, Igor; Sattar, Naveed; Sever, Peter; Sinner, Moritz F; Soliman, Elsayed Z; Spector, Timothy D; Stanton, Alice V; Stirrups, Kathleen E; Taylor, Kent D; Tobin, Martin D; Uitterlinden, André; Vaartjes, Ilonca; Hoes, Arno W; van der Meer, Peter; Völker, Uwe; Waldenberger, Melanie; Xie, Zhijun; Zoledziewska, Magdalena; Tinker, Andrew; Polasek, Ozren; Rosand, Jonathan; Jamshidi, Yalda; van Duijn, Cornelia M; Zeggini, Eleftheria; Jukema, J Wouter; Asselbergs, Folkert W; Samani, Nilesh J; Lehtimäki, Terho; Gudnason, Vilmundur; Wilson, James; Lubitz, Steven A; Kääb, Stefan; Sotoodehnia, Nona; Caulfield, Mark J; Palmer, Colin N A; Sanna, Serena; Mook-Kanamori, Dennis O; Deloukas, Panos; Pedersen, Oluf; Rotter, Jerome I; Dörr, Marcus; O'Donnell, Chris J; Hayward, Caroline; Arking, Dan E; Kooperberg, Charles; van der Harst, Pim; Eijgelsheim, Mark; Stricker, Bruno H; Munroe, Patricia B

2017-06-15

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies. © The Author 2017. Published by Oxford University Press.

Quasi-causal associations of physical activity and neighborhood walkability with body mass index: a twin study.

PubMed

Duncan, Glen E; Cash, Stephanie Whisnant; Horn, Erin E; Turkheimer, Eric

2015-01-01

Physical activity, neighborhood walkability, and body mass index (BMI, kg/m(2)) associations were tested using quasi-experimental twin methods. We hypothesized that physical activity and walkability were independently associated with BMI within twin pairs, controlling for genetic and environmental background shared between them. Data were from 6376 (64% female; 58% identical) same-sex pairs, University of Washington Twin Registry, 2008-2013. Neighborhood walking, moderate-to-vigorous physical activity (MVPA), and BMI were self-reported. Residential address was used to calculate walkability. Phenotypic (non-genetically informed) and biometric (genetically informed) regression was employed, controlling for age, sex, and race. Walking and MVPA were associated with BMI in phenotypic analyses; associations were attenuated but significant in biometric analyses (Ps<0.05). Walkability was not associated with BMI, however, was associated with walking (but not MVPA) in both phenotypic and biometric analyses (Ps<0.05), with no attenuation accounting for shared genetic and environmental background. The association between activity and BMI is largely due to shared genetic and environmental factors, but a significant causal relationship remains accounting for shared background. Although walkability is not associated with BMI, it is associated with neighborhood walking (but not MVPA) accounting for shared background, suggesting a causal relationship between them. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationship between the built environment and physical activity levels: The Harvard Alumni Health Study

PubMed Central

Lee, I-Min; Ewing, Reid; Sesso, Howard D.

2009-01-01

Background Physical activity is associated with better health, but many individuals are insufficiently active. Modifying the built environment may be an approach capable of influencing population-wide levels of physical activity, but few data exist from longitudinal studies that can minimize bias from active persons choosing activity-friendly neighborhoods. This is the first large-scale study to examine longitudinal changes in the built environment and physical activity. Methods This study examined cross-sectional associations between urban sprawl (mapping addresses to corresponding counties) and physical activity (self-reported) among men throughout the US in 1993 and in 1988, and longitudinal associations between changes in exposure to urban sprawl for movers and physical activity, 1988-1993. Included were 4,997 men (mean age, 70 years) in the 1993 cross-sectional study; 4,918 men in the 1988 cross-sectional study; and 3,448 men in the longitudinal study, 1988-1993. Data were collected prospectively in 1988 and 1993, and analyses were performed in 2007-2008. Results In cross-sectional analyses, less sprawl was significantly associated with more walking (odds ratios (OR), comparing least with most sprawling areas, for meeting physical activity recommendations by walking = 1.38 [95% confidence interval = 1.09, 1.76] in 1993 and 1.53 [1.19, 1.96] in 1988). Less sprawl also was associated with lower prevalence of overweight (corresponding OR = 0.79 [0.64, 0.98] in 1993 and 0.81 [0.66-1.00] in 1988). However, longitudinal analyses assessing change did not show that decreasing sprawl was associated with increased physical activity or decreased body mass index. Conclusions These findings suggest that the cross-sectional results may reflect self-selection, rather than indicating that the built environment – as measured by urban sprawl – increases physical activity. However, the longitudinal findings were limited by small numbers of men changing residence and associated sprawl levels. PMID:19765500

A recessive genetic model and runs of homozygosity in major depressive disorder

PubMed Central

Power, Robert A.; Keller, Matthew C.; Ripke, Stephan; Abdellaoui, Abdel; Wray, Naomi R.; Sullivan, Patrick F; Breen, Gerome

2014-01-01

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here we undertake an analysis of ROH for MDD using the 9,238 MDD cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (p=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD. PMID:24482242

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.

PubMed

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke; Freathy, Rachel M

2018-02-15

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. © The Author(s) 2018. Published by Oxford University Press.

Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

PubMed Central

Beaumont, Robin N; Warrington, Nicole M; Cavadino, Alana; Tyrrell, Jessica; Nodzenski, Michael; Horikoshi, Momoko; Geller, Frank; Myhre, Ronny; Richmond, Rebecca C; Paternoster, Lavinia; Bradfield, Jonathan P; Kreiner-Møller, Eskil; Huikari, Ville; Metrustry, Sarah; Lunetta, Kathryn L; Painter, Jodie N; Hottenga, Jouke-Jan; Allard, Catherine; Barton, Sheila J; Espinosa, Ana; Marsh, Julie A; Potter, Catherine; Zhang, Ge; Ang, Wei; Berry, Diane J; Bouchard, Luigi; Das, Shikta; Hakonarson, Hakon; Heikkinen, Jani; Helgeland, Øyvind; Hocher, Berthold; Hofman, Albert; Inskip, Hazel M; Jones, Samuel E; Kogevinas, Manolis; Lind, Penelope A; Marullo, Letizia; Medland, Sarah E; Murray, Anna; Murray, Jeffrey C; Njølstad, Pål R; Nohr, Ellen A; Reichetzeder, Christoph; Ring, Susan M; Ruth, Katherine S; Santa-Marina, Loreto; Scholtens, Denise M; Sebert, Sylvain; Sengpiel, Verena; Tuke, Marcus A; Vaudel, Marc; Weedon, Michael N; Willemsen, Gonneke; Wood, Andrew R; Yaghootkar, Hanieh; Muglia, Louis J; Bartels, Meike; Relton, Caroline L; Pennell, Craig E; Chatzi, Leda; Estivill, Xavier; Holloway, John W; Boomsma, Dorret I; Montgomery, Grant W; Murabito, Joanne M; Spector, Tim D; Power, Christine; Järvelin, Marjo-Ritta; Bisgaard, Hans; Grant, Struan F A; Sørensen, Thorkild I A; Jaddoe, Vincent W; Jacobsson, Bo; Melbye, Mads; McCarthy, Mark I; Hattersley, Andrew T; Hayes, M Geoffrey; Frayling, Timothy M; Hivert, Marie-France; Felix, Janine F; Hyppönen, Elina; Lowe, William L; Evans, David M; Lawlor, Debbie A; Feenstra, Bjarke

2018-01-01

Abstract Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10−8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights. PMID:29309628

Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

2010-01-01

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

Validation of the Spanish Version of the Psychological Sense of School Membership (PSSM) Scale in Chilean Adolescents and Its Association with School-Related Outcomes and Substance Use

PubMed Central

Gaete, Jorge; Montero-Marin, Jesus; Rojas-Barahona, Cristian A.; Olivares, Esterbina; Araya, Ricardo

2016-01-01

School membership appears to be an important factor in explaining the relationship between students and schools, including school staff. School membership is associated with several school-related outcomes, such as academic performance and expectations. Most studies on school membership have been conducted in developed countries. The Psychological Sense of School Membership (PSSM) scale (18 items: 13 positively worded items, 5 negatively worded items) has been widely used to measure this construct, but no studies regarding its validity and reliability have been conducted in Spanish-speaking Latin American countries. This study investigates the psychometric properties, factor structure and reliability of this scale in a sample of 1250 early adolescents in Chile. Both exploratory and confirmatory factor analyses provide evidence of an excellent fit for a one-factor solution after removing the negatively worded items. The internal consistency of this new abbreviated version was 0.92. The association analyses demonstrated that high school membership was associated with better academic performance, stronger school bonding, a reduced likelihood of school misbehavior, and reduced likelihood of substance use. Analyses showed support for the reliability and validity of the PSSM among Chilean adolescents. PMID:27999554

Maternal work early in the lives of children and its distal associations with achievement and behavior problems: a meta-analysis.

PubMed

Lucas-Thompson, Rachel G; Goldberg, Wendy A; Prause, JoAnn

2010-11-01

This meta-analysis of 69 studies (1,483 effect sizes) used random effects models to examine maternal employment during infancy/early childhood in relation to 2 major domains of child functioning: achievement and behavior problems. Analyses of studies that spanned 5 decades indicated that, with a few exceptions, early employment was not significantly associated with later achievement or internalizing/externalizing behaviors. The exceptions were for teacher ratings of achievement and internalizing behaviors: Employment was associated with higher achievement and fewer internalizing behaviors. Substantial heterogeneity among the effect sizes prompted examination of moderators. Sample-level moderator analyses pointed to the importance of socioeconomic and contextual variables, with early employment most beneficial when families were challenged by single parenthood or welfare status. Maternal employment during Years 2 and 3 was associated with higher achievement. Some moderator analyses indicated negative effects of employment for middle-class and 2-parent families and for very early employment (child's first year). Associations also differed depending on whether effect sizes were adjusted for contextual variables. Only 1 study-level moderator (sex of first author) was significant after adjusting for other moderators. The small effect size and primarily nonsignificant results for main effects of early maternal employment should allay concerns about mothers working when children are young. However, negative findings associated with employment during the child's first year are compatible with calls for more generous maternal leave policies. Results highlight the importance of social context for identifying under which conditions and for which subgroups early maternal employment is associated with positive or negative child outcomes.

Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses

PubMed Central

Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

2016-01-01

Objective To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. Data sources A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Study eligibility criteria Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Outcome measures Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. Results 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. Conclusions This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living with HIV. PMID:27412106

Association of objectively measured arm inclination with shoulder pain: A 6-month follow-up prospective study of construction and health care workers.

PubMed

Koch, Markus; Lunde, Lars-Kristian; Veiersted, Kaj Bo; Knardahl, Stein

2017-01-01

The aim was to determine the association of occupational arm inclination with shoulder pain in construction and health care workers. Arm inclination relative to the vertical was measured with an accelerometer placed on the dominant upper arm for up to four full days at baseline in 62 construction workers and 63 health care workers. The pain intensity in the shoulder and mechanical and psychosocial work factors were measured by self-reports at baseline and prospectively after 6 months. The associations between exposures and shoulder pain were analyzed with multilevel mixed-effects linear regressions. For the total study population working with the dominant arm at inclinations > 30° and >120° was associated with lower levels of shoulder pain both cross-sectionally and after 6 months. Associations were attenuated when adjusting for individual and social factors, psychological state, and exposure during leisure time, especially for the high inclination levels. Analyses, only including subjects with no pain at baseline revealed no significant associations. While stratified analysis showed negative associations in the construction worker group, there were no significant association in health care workers. Compared to the number of hypotheses tested, the number of significant findings was low. Adjustment by Bonferroni-correction made almost all findings insignificant. All analyses reflected a negative association between arm inclination and shoulder pain, but few analyses showed these associations to be statistically significant. If there is a relationship between arm inclination and shoulder pain, these findings could indicate that pain-avoidance may modify how workers perform their tasks.

Association of objectively measured arm inclination with shoulder pain: A 6-month follow-up prospective study of construction and health care workers

PubMed Central

Koch, Markus; Lunde, Lars-Kristian; Veiersted, Kaj Bo; Knardahl, Stein

2017-01-01

Objectives The aim was to determine the association of occupational arm inclination with shoulder pain in construction and health care workers. Methods Arm inclination relative to the vertical was measured with an accelerometer placed on the dominant upper arm for up to four full days at baseline in 62 construction workers and 63 health care workers. The pain intensity in the shoulder and mechanical and psychosocial work factors were measured by self-reports at baseline and prospectively after 6 months. The associations between exposures and shoulder pain were analyzed with multilevel mixed-effects linear regressions. Results For the total study population working with the dominant arm at inclinations > 30° and >120° was associated with lower levels of shoulder pain both cross-sectionally and after 6 months. Associations were attenuated when adjusting for individual and social factors, psychological state, and exposure during leisure time, especially for the high inclination levels. Analyses, only including subjects with no pain at baseline revealed no significant associations. While stratified analysis showed negative associations in the construction worker group, there were no significant association in health care workers. Compared to the number of hypotheses tested, the number of significant findings was low. Adjustment by Bonferroni-correction made almost all findings insignificant. Conclusions All analyses reflected a negative association between arm inclination and shoulder pain, but few analyses showed these associations to be statistically significant. If there is a relationship between arm inclination and shoulder pain, these findings could indicate that pain-avoidance may modify how workers perform their tasks. PMID:29176761

Practicing Dentists’ Self-Efficacy and Associated Factors in Managing the Treatment of Adults with Mental and Physical Disabilities: An Exploratory Cross-Sectional Study in Riyadh, Saudi Arabia

PubMed Central

AlQahtani, Sakher; Zakaria Murshid, Ebtissam; Kassim, Saba

2017-01-01

Background: Provision of oral healthcare to adults with mental and physical disabilities (AMPD) remains a challenging area across various healthcare systems. The present study aimed to assess self-reported efficacy and investigate factors associated with self-efficacy in the management of AMPD among practicing dentists in Saudi Arabia. Methods: A pilot-tested, self-administered questionnaire was distributed to a convenience sample of 1000 dentists. Descriptive and inferential analyses were performed on the collected responses. Results: Among the respondents (54%), 43% were males. Only 14% described their self-efficacy in managing AMPD as “High”. Multivariable regression analyses revealed significant associations between “High” self-efficacy and male gender (Odd ratio (OR) = 2.39, 95% CI = 1.16–4.89), experience practicing dentistry for 11 years or more (OR = 2.19, 95% CI = 1.04–4.47), specialization in pediatric dentistry (OR = 3.98, 95% CI = 1.31–12.07), previous experience in managing AMPD (OR = 4.23, 95% CI = 1.59–11.22), and awareness of regulations for managing AMPD (OR = 2.62, 95% CI = 1.42–4.38). The interaction of gender x age was significantly associated (p = 0.028) with “High” self-efficacy. Gender-stratified analyses revealed a significant association between age and “High” self-efficacy among male dentists only. Conclusions: The findings of the present study highlight that a large percentage of dentists reported “Low/Moderate” self-efficacy in managing AMPD, particularly among female dentists. However, further studies are required to verify the factors associated with self-efficacy in the present study, and to identify other factors that may influence self-efficacy in managing AMPD. PMID:29232884

Practicing Dentists' Self-Efficacy and Associated Factors in Managing the Treatment of Adults with Mental and Physical Disabilities: An Exploratory Cross-Sectional Study in Riyadh, Saudi Arabia.

PubMed

AlQahtani, Sakher; Murshid, Ebtissam Zakaria; Fadel, Hani Talal; Kassim, Saba

2017-12-11

Background: Provision of oral healthcare to adults with mental and physical disabilities (AMPD) remains a challenging area across various healthcare systems. The present study aimed to assess self-reported efficacy and investigate factors associated with self-efficacy in the management of AMPD among practicing dentists in Saudi Arabia. Methods: A pilot-tested, self-administered questionnaire was distributed to a convenience sample of 1000 dentists. Descriptive and inferential analyses were performed on the collected responses. Results: Among the respondents (54%), 43% were males. Only 14% described their self-efficacy in managing AMPD as "High". Multivariable regression analyses revealed significant associations between "High" self-efficacy and male gender (Odd ratio (OR) = 2.39, 95% CI = 1.16-4.89), experience practicing dentistry for 11 years or more (OR = 2.19, 95% CI = 1.04-4.47), specialization in pediatric dentistry (OR = 3.98, 95% CI = 1.31-12.07), previous experience in managing AMPD (OR = 4.23, 95% CI = 1.59-11.22), and awareness of regulations for managing AMPD (OR = 2.62, 95% CI = 1.42-4.38). The interaction of gender x age was significantly associated ( p = 0.028) with "High" self-efficacy. Gender-stratified analyses revealed a significant association between age and "High" self-efficacy among male dentists only. Conclusions: The findings of the present study highlight that a large percentage of dentists reported "Low/Moderate" self-efficacy in managing AMPD, particularly among female dentists. However, further studies are required to verify the factors associated with self-efficacy in the present study, and to identify other factors that may influence self-efficacy in managing AMPD.

Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes

PubMed Central

Kennedy, Oliver J; Roderick, Paul; Fallowfield, Jonathan A; Hayes, Peter C; Parkes, Julie

2017-01-01

Objectives To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes. Design Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome. Data sources PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references. Eligibility criteria for selecting studies Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded. Results The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83, 95% confidence interval 0.83 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99). There was also an association between coffee drinking and risk of fracture in women but not in men. Conclusion Coffee consumption seems generally safe within usual levels of intake, with summary estimates indicating largest risk reduction for various health outcomes at three to four cups a day, and more likely to benefit health than harm. Robust randomised controlled trials are needed to understand whether the observed associations are causal. Importantly, outside of pregnancy, existing evidence suggests that coffee could be tested as an intervention without significant risk of causing harm. Women at increased risk of fracture should possibly be excluded. PMID:29167102

Systematic Review of the Cost and Cost-Effectiveness of Rapid Endovascular Therapy for Acute Ischemic Stroke.

PubMed

Sevick, Laura K; Ghali, Sarah; Hill, Michael D; Danthurebandara, Vishva; Lorenzetti, Diane L; Noseworthy, Tom; Spackman, Eldon; Clement, Fiona

2017-09-01

Rapid endovascular therapy (EVT) is an emerging treatment option for acute ischemic stroke. Several economic evaluations have been published examining the cost-effectiveness of EVT, and many international bodies are currently making adoption decisions. The objective of this study was to establish the cost-effectiveness of EVT for ischemic stroke patients and to synthesize all the publicly available economic literature. A systematic review of the published literature was conducted to identify economic evaluations and cost analyses of EVT for acute ischemic stroke patients. Systematic review best practices were followed, and study quality was assessed. Four-hundred sixty-three articles were identified from electronic databases. After deduplication, abstract review, and full-text review, 17 studies were included. Seven of the studies were cost analyses, and 10 were cost-effectiveness studies. Generally, the cost analyses reported on the cost of the approach/procedure or the hospitalization costs associated with EVT. All of the cost-effectiveness studies reported a cost per quality-adjusted life year as the primary outcomes. Studies varied in regards to the costs considered, the perspective adopted, and the time horizon used. All the studies reported a cost per quality-adjusted life year of <$50 000 as the primary outcome. There is a robust body of evidence for the cost and cost-effectiveness of EVT. The cost analyses suggested that although EVT was associated with higher costs, it also resulted in improved patient outcomes. From the cost-effectiveness studies, EVT seems to be good value for money when a threshold of $50 000 per quality-adjusted life year gained is adopted. © 2017 American Heart Association, Inc.

A Genetically Informed Study of the Processes Underlying the Association between Parental Marital Instability and Offspring Adjustment

ERIC Educational Resources Information Center

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Slutske, Wendy S.; Heath, Andrew C.; Madden, Pamela A.; Martin, Nicholas G.

2006-01-01

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental…

Genetic variants associated with subjective well-being, depressive symptoms and neuroticism identified through genome-wide analyses

PubMed Central

Derringer, Jaime; Gratten, Jacob; Lee, James J; Liu, Jimmy Z; de Vlaming, Ronald; Ahluwalia, Tarunveer S; Buchwald, Jadwiga; Cavadino, Alana; Frazier-Wood, Alexis C; Davies, Gail; Furlotte, Nicholas A; Garfield, Victoria; Geisel, Marie Henrike; Gonzalez, Juan R; Haitjema, Saskia; Karlsson, Robert; van der Laan, Sander W; Ladwig, Karl-Heinz; Lahti, Jari; van der Lee, Sven J; Miller, Michael B; Lind, Penelope A; Liu, Tian; Matteson, Lindsay; Mihailov, Evelin; Minica, Camelia C; Nolte, Ilja M; Mook-Kanamori, Dennis O; van der Most, Peter J; Oldmeadow, Christopher; Qian, Yong; Raitakari, Olli; Rawal, Rajesh; Realo, Anu; Rueedi, Rico; Schmidt, Börge; Smith, Albert V; Stergiakouli, Evie; Tanaka, Toshiko; Taylor, Kent; Thorleifsson, Gudmar; Wedenoja, Juho; Wellmann, Juergen; Westra, Harm-Jan; Willems, Sara M; Zhao, Wei; Amin, Najaf; Bakshi, Andrew; Bergmann, Sven; Bjornsdottir, Gyda; Boyle, Patricia A; Cherney, Samantha; Cox, Simon R; Davis, Oliver S P; Ding, Jun; Direk, Nese; Eibich, Peter; Emeny, Rebecca T; Fatemifar, Ghazaleh; Faul, Jessica D; Ferrucci, Luigi; Forstner, Andreas J; Gieger, Christian; Gupta, Richa; Harris, Tamara B; Harris, Juliette M; Holliday, Elizabeth G; Hottenga, Jouke-Jan; De Jager, Philip L; Kaakinen, Marika A; Kajantie, Eero; Karhunen, Ville; Kolcic, Ivana; Kumari, Meena; Launer, Lenore J; Franke, Lude; Li-Gao, Ruifang; Liewald, David C; Koini, Marisa; Loukola, Anu; Marques-Vidal, Pedro; Montgomery, Grant W; Mosing, Miriam A; Paternoster, Lavinia; Pattie, Alison; Petrovic, Katja E; Pulkki-Råback, Laura; Quaye, Lydia; Räikkönen, Katri; Rudan, Igor; Scott, Rodney J; Smith, Jennifer A; Sutin, Angelina R; Trzaskowski, Maciej; Vinkhuyzen, Anna E; Yu, Lei; Zabaneh, Delilah; Attia, John R; Bennett, David A; Berger, Klaus; Bertram, Lars; Boomsma, Dorret I; Snieder, Harold; Chang, Shun-Chiao; Cucca, Francesco; Deary, Ian J; van Duijn, Cornelia M; Eriksson, Johan G; Bültmann, Ute; de Geus, Eco J C; Groenen, Patrick J F; Gudnason, Vilmundur; Hansen, Torben; Hartman, Catharine A; Haworth, Claire M A; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Hyppönen, Elina; Iacono, William G; Järvelin, Marjo-Riitta; Jöckel, Karl-Heinz; Kaprio, Jaakko; Kardia, Sharon L R; Keltikangas-Järvinen, Liisa; Kraft, Peter; Kubzansky, Laura D; Lehtimäki, Terho; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; Metspalu, Andres; Mills, Melinda; de Mutsert, Renée; Oldehinkel, Albertine J; Pasterkamp, Gerard; Pedersen, Nancy L; Plomin, Robert; Polasek, Ozren; Power, Christine; Rich, Stephen S; Rosendaal, Frits R; den Ruijter, Hester M; Schlessinger, David; Schmidt, Helena; Svento, Rauli; Schmidt, Reinhold; Alizadeh, Behrooz Z; Sørensen, Thorkild I A; Spector, Tim D; Starr, John M; Stefansson, Kari; Steptoe, Andrew; Terracciano, Antonio; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tiemeier, Henning; Uitterlinden, André G; Vollenweider, Peter; Wagner, Gert G; Weir, David R; Yang, Jian; Conley, Dalton C; Smith, George Davey; Hofman, Albert; Johannesson, Magnus; Laibson, David I; Medland, Sarah E; Meyer, Michelle N; Pickrell, Joseph K; Esko, Tõnu; Krueger, Robert F; Beauchamp, Jonathan P; Koellinger, Philipp D; Benjamin, Daniel J; Bartels, Meike; Cesarini, David

2016-01-01

We conducted genome-wide association studies of three phenotypes: subjective well-being (N = 298,420), depressive symptoms (N = 161,460), and neuroticism (N = 170,910). We identified three variants associated with subjective well-being, two with depressive symptoms, and eleven with neuroticism, including two inversion polymorphisms. The two depressive symptoms loci replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings, and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal/pancreas tissues are strongly enriched for association. PMID:27089181

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry

PubMed Central

Benjamin, Emelia J.; Rice, Kenneth M.; Arking, Dan E.; Pfeufer, Arne; van Noord, Charlotte; Smith, Albert V.; Schnabel, Renate B.; Bis, Joshua C.; Boerwinkle, Eric; Sinner, Moritz F.; Dehghan, Abbas; Lubitz, Steven A.; D’Agostino, Ralph B.; Lumley, Thomas; Ehret, Georg B.; Heeringa, Jan; Aspelund, Thor; Newton-Cheh, Christopher; Larson, Martin G.; Marciante, Kristin D.; Soliman, Elsayed Z.; Rivadeneira, Fernando; Wang, Thomas J.; Eiriksdottir, Gudny; Levy, Daniel; Psaty, Bruce M.; Li, Man; Chamberlain, Alanna M.; Hofman, Albert; Vasan, Ramachandran S.; Harris, Tamara B.; Rotter, Jerome I.; Kao, W.H. Linda; Agarwal, Sunil K.; Ch. Stricker, Bruno H.; Wang, Ke; Launer, Lenore J.; Smith, Nicholas L.; Chakravarti, Aravinda; Uitterlinden, Andre G.; Wolf, Philip A; Sotoodehnia, Nona; Kottgen, Anna; van Duijn, Cornelia M.; Lunetta, Kathryn L.; Heckbert, Susan R.; Gudnason, Vilmundur; Alonso, Alvaro; Kaab, Stefan; Ellinor, Patrick T.; Witteman, Jacqueline C.

2009-01-01

We conducted meta-analyses of genome-wide association studies (GWAS) for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a novel locus for AF (ZFHX3, rs2106261, risk ratio [RR]=1.19; P=2.3×10−7), an association that was replicated in the German AF Network (odds ratio=1.44; P=1.6×10−11). Combining the discovery and replication results, rs2106261 was significantly associated with AF (RR=1.25; P=1.8×10−15). PMID:19597492

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

PubMed

Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; van Leeuwen, Flora E; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Menéndez Rodríguez, Primitiva; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A; Henderson, Brian E; Le Marchand, Loic; Kolonel, Laurence N; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M A; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E; Ørsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E; Hunter, David J; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P E A; Tollenaar, R A E M; Seynaeve, C; Dite, Gillian S; Apicella, Carmel; Hopper, John L; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D; Southey, Melissa C; Humphreys, Manjeet K; Easton, Douglas; Pharoah, Paul; Sherman, Mark E; Garcia-Closas, Montserrat

2011-02-02

Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

PubMed Central

Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

2011-01-01

Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. Conclusions This study shows that reproductive factors and BMI are most clearly associated with hormone receptor–positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology. PMID:21191117

Brief Motivational Interventions Are Associated With Reductions in Alcohol-Impaired Driving Among College Drinkers.

PubMed

Teeters, Jenni B; Borsari, Brian; Martens, Matthew P; Murphy, James G

2015-09-01

Alcohol-impaired (AI) driving among college students remains a significant public health concern and may be the single most risky drinking outcome among young adults. Brief motivational interventions (BMIs) have been shown to reduce alcohol use and problems, but their specific efficacy for decreasing AI driving among college students is unknown. The present study analyzed data from three randomized controlled trials of BMI (Murphy et al., 2010: n = 74; Borsari et al., 2012: n = 530; and Martens et al., 2013: n = 365) to evaluate whether BMIs are associated with reductions in AI driving among college student drinkers. Participants in all three studies were randomized to BMI or control conditions. Participants reported whether they had driven under the influence (yes/no) following the BMI over the follow-up period. Separate binary logistic regression analyses were conducted for each study. For Studies 1 and 2, these analyses revealed that a BMI was significantly associated with reductions in AI driving at the final (6-month and 9-month, respectively) follow-up compared with the control condition. For Study 3, analyses revealed that a single-component BMI focused on the correction of misperceptions of descriptive norms was significantly associated with reductions in AI driving compared with the control group at the final (6-month) followup, whereas a single-component BMI focused on the use of protective behavioral strategies was not. Change in drinking level did not mediate the relationship between the condition and the change in AI driving. Counselor-administered BMIs that include descriptive normative feedback are associated with significant reductions in AI driving compared with control.

Egg consumption and risk of bladder cancer: a meta-analysis.

PubMed

Li, Fei; Zhou, You; Hu, Rui-ting; Hou, Li-na; Du, Yue-Jun; Zhang, Xin-ji; Olkkonen, Vesa M; Tan, Wan-long

2013-01-01

The findings of epidemiologic studies on the association between egg consumption and bladder cancer risk remain conflicting. We conducted a meta-analysis to clarify the potential association between egg consumption and bladder cancer risk. Four cohort studies and 9 case-control studies in the PubMed database through February 2012 were identified on egg consumption and risk of bladder cancer involving 2715 cases and 184,727 participants. Random-effects models were used to calculate the summary relative risk estimates (SRRE) based on the highest compared with the lowest category of egg consumption. In addition, we performed stratified analyses and sensitivity and dose-response analyses to examine the association. Overall, no significant association was observed between egg consumption and bladder cancer (SRRE = 1.11 95% CI: 0.90-1.35). However, increased risk of bladder cancer was detected in North/South America (SRRE = 1.40 95% CI: 1.05-1.86) and, moreover, fried egg intake positively associated with bladder cancer as well (SRRE = 2.04, 95% CI: 1.41-2.95). In conclusion, our findings suggest no significant association between egg consumption and bladder cancer risk, except for a possible positive relationship with the intake of fried eggs based on the limited number of studies. Additional studies, especially large prospective cohort studies, are warranted to confirm these findings.

Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array.

PubMed

Saunders, Edward J; Dadaev, Tokhir; Leongamornlert, Daniel A; Al Olama, Ali Amin; Benlloch, Sara; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Borge G; Travis, Ruth C; Neal, David; Pasayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen N; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong Y; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Govindasami, Koveela; Muir, Ken; Easton, Douglas F; Eeles, Rosalind A; Kote-Jarai, Zsofia

2016-04-12

Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas two of B100 common, low-penetrance PrCa susceptibility variants identified so far by genome-wide association studies implicate RAD51B and RAD23B. Genotype data from the iCOGS array were imputed to the 1000 genomes phase 3 reference panel for 21 780 PrCa cases and 21 727 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. We subsequently performed single variant, gene and pathway-level analyses using 81 303 SNPs within 20 Kb of a panel of 179 DNA-repair genes. Single SNP analyses identified only the previously reported association with RAD51B. Gene-level analyses using the SKAT-C test from the SNP-set (Sequence) Kernel Association Test (SKAT) identified a significant association with PrCa for MSH5. Pathway-level analyses suggested a possible role for the translesion synthesis pathway in PrCa risk and Homologous recombination/Fanconi Anaemia pathway for PrCa aggressiveness, even though after adjustment for multiple testing these did not remain significant. MSH5 is a novel candidate gene warranting additional follow-up as a prospective PrCa-risk locus. MSH5 has previously been reported as a pleiotropic susceptibility locus for lung, colorectal and serous ovarian cancers.

No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis

PubMed Central

Loley, Christina; Alver, Maris; Assimes, Themistocles L.; Bjonnes, Andrew; Goel, Anuj; Gustafsson, Stefan; Hernesniemi, Jussi; Hopewell, Jemma C.; Kanoni, Stavroula; Kleber, Marcus E.; Lau, King Wai; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Nelson, Christopher P.; Nikpay, Majid; Qu, Liming; Salfati, Elias; Scholz, Markus; Tukiainen, Taru; Willenborg, Christina; Won, Hong-Hee; Zeng, Lingyao; Zhang, Weihua; Anand, Sonia S.; Beutner, Frank; Bottinger, Erwin P.; Clarke, Robert; Dedoussis, George; Do, Ron; Esko, Tõnu; Eskola, Markku; Farrall, Martin; Gauguier, Dominique; Giedraitis, Vilmantas; Granger, Christopher B.; Hall, Alistair S.; Hamsten, Anders; Hazen, Stanley L.; Huang, Jie; Kähönen, Mika; Kyriakou, Theodosios; Laaksonen, Reijo; Lind, Lars; Lindgren, Cecilia; Magnusson, Patrik K. E.; Marouli, Eirini; Mihailov, Evelin; Morris, Andrew P.; Nikus, Kjell; Pedersen, Nancy; Rallidis, Loukianos; Salomaa, Veikko; Shah, Svati H.; Stewart, Alexandre F. R.; Thompson, John R.; Zalloua, Pierre A.; Chambers, John C.; Collins, Rory; Ingelsson, Erik; Iribarren, Carlos; Karhunen, Pekka J.; Kooner, Jaspal S.; Lehtimäki, Terho; Loos, Ruth J. F.; März, Winfried; McPherson, Ruth; Metspalu, Andres; Reilly, Muredach P.; Ripatti, Samuli; Sanghera, Dharambir K.; Thiery, Joachim; Watkins, Hugh; Deloukas, Panos; Kathiresan, Sekar; Samani, Nilesh J.; Schunkert, Heribert; Erdmann, Jeanette; König, Inke R.

2016-01-01

In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD. PMID:27731410

Microwave power transmission system studies. Volume 2: Introduction, organization, environmental and spaceborne systems analyses

NASA Technical Reports Server (NTRS)

Maynard, O. E.; Brown, W. C.; Edwards, A.; Haley, J. T.; Meltz, G.; Howell, J. M.; Nathan, A.

1975-01-01

Introduction, organization, analyses, conclusions, and recommendations for each of the spaceborne subsystems are presented. Environmental effects - propagation analyses are presented with appendices covering radio wave diffraction by random ionospheric irregularities, self-focusing plasma instabilities and ohmic heating of the D-region. Analyses of dc to rf conversion subsystems and system considerations for both the amplitron and the klystron are included with appendices for the klystron covering cavity circuit calculations, output power of the solenoid-focused klystron, thermal control system, and confined flow focusing of a relativistic beam. The photovoltaic power source characteristics are discussed as they apply to interfacing with the power distribution flow paths, magnetic field interaction, dc to rf converter protection, power distribution including estimates for the power budget, weights, and costs. Analyses for the transmitting antenna consider the aperture illumination and size, with associated efficiencies and ground power distributions. Analyses of subarray types and dimensions, attitude error, flatness, phase error, subarray layout, frequency tolerance, attenuation, waveguide dimensional tolerances, mechanical including thermal considerations are included. Implications associated with transportation, assembly and packaging, attitude control and alignment are discussed. The phase front control subsystem, including both ground based pilot signal driven adaptive and ground command approaches with their associated phase errors, are analyzed.

Incidence of phlebitis and post-infusion phlebitis in hospitalised adults.

PubMed

Urbanetto, Janete de Souza; Muniz, Franciele de Oliveira Minuto; Silva, Renata Martins da; Freitas, Ana Paula Christo de; Oliveira, Ana Paula Ribeiro de; Santos, Jessica de Cassia Ramos Dos

2017-06-29

to determine the incidence of phlebitis during and after the use of peripheral intravenous catheter (PIC), and analyse the association of this complication with risk factors. cohort study with 165 adult patients admitted to a university hospital in Porto Alegre, totalling 447 accesses, from December 2014 to February 2015. Data were collected on a daily basis and analysed by means of descriptive and analytical statistics. The incidence of phlebitis during PIC was 7.15% and the incidence of post-infusion phlebitis was 22.9%. Phlebitis during catheter use was associated with the use of Amoxicillin + Clavulanic Acid. The grade of post-infusion phlebitis was associated with age and use of Amoxicillin + Clavulanic Acid, Tramadol Hydrochloride, and Amphotericin. The incidence of post-infusion phlebitis proved to be an important indicator to analyse the quality of the healthcare setting.

Integrative analysis of micro-RNA, gene expression, and survival of glioblastoma multiforme.

PubMed

Huang, Yen-Tsung; Hsu, Thomas; Kelsey, Karl T; Lin, Chien-Ling

2015-02-01

Glioblastoma multiforme (GBM), the most common type of malignant brain tumor, is highly fatal. Limited understanding of its rapid progression necessitates additional approaches that integrate what is known about the genomics of this cancer. Using a discovery set (n = 348) and a validation set (n = 174) of GBM patients, we performed genome-wide analyses that integrated mRNA and micro-RNA expression data from GBM as well as associated survival information, assessing coordinated variability in each as this reflects their known mechanistic functions. Cox proportional hazards models were used for the survival analyses, and nonparametric permutation tests were performed for the micro-RNAs to investigate the association between the number of associated genes and its prognostication. We also utilized mediation analyses for micro-RNA-gene pairs to identify their mediation effects. Genome-wide analyses revealed a novel pattern: micro-RNAs related to more gene expressions are more likely to be associated with GBM survival (P = 4.8 × 10(-5)). Genome-wide mediation analyses for the 32,660 micro-RNA-gene pairs with strong association (false discovery rate [FDR] < 0.01%) identified 51 validated pairs with significant mediation effect. Of the 51 pairs, miR-223 had 16 mediation genes. These 16 mediation genes of miR-223 were also highly associated with various other micro-RNAs and mediated their prognostic effects as well. We further constructed a gene signature using the 16 genes, which was highly associated with GBM survival in both the discovery and validation sets (P = 9.8 × 10(-6)). This comprehensive study discovered mediation effects of micro-RNA to gene expression and GBM survival and provided a new analytic framework for integrative genomics. © 2014 WILEY PERIODICALS, INC.

Head circumference at birth and childhood developmental disorders in a nationwide cohort in Denmark.

PubMed

Aagaard, Kristina; Bach, Cathrine Carlsen; Henriksen, Tine Brink; Larsen, René Tidemand; Matthiesen, Niels Bjerregård

2018-06-08

Early markers of Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) may improve the understanding and early recognition of these disorders. We aimed to estimate the association between head circumference at birth, a measure of cerebral size at birth, and the risk of ADHD and ASD. We present a register-based cohort study of all Danish singletons born alive between 1997 and 2013. Cox proportional hazards regression was used for the statistical analyses. Sibling-matched analyses were performed to account for unmeasured confounding shared by siblings. The analyses included 986 909 new-borns. Compared to normocephalic children, microcephaly was associated with an increased risk of ADHD (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.12, 1.32). Macrocephaly was associated with a decreased risk of ADHD (HR 0.90, 95% CI 0.82, 0.99). Neither microcephaly nor macrocephaly were associated with ASD (HR 1.06, 95% CI 0.94, 1.19 and 1.03, 95% CI 0.90, 1.19). The largest difference was found within the normocephalic children. A head circumference at the lower limit of normocephaly compared to a head circumference at the upper limit was associated with an increased risk of ADHD (HR 1.52, 95% CI 1.43, 1.63). The sibling analyses confirmed the increased risk of ADHD with decreasing head circumference in the normocephalic children. No other clear associations were present in the sibling analyses. Within normocephalic children, smaller head circumference at birth was associated with a higher risk of ADHD. Restricted foetal brain growth may be a risk factor for the development of ADHD but not ASD. © 2018 John Wiley & Sons Ltd.

Metagenomic analyses of bacteria on human hairs: a qualitative assessment for applications in forensic science.

PubMed

Tridico, Silvana R; Murray, Dáithí C; Addison, Jayne; Kirkbride, Kenneth P; Bunce, Michael

2014-01-01

Mammalian hairs are one of the most ubiquitous types of trace evidence collected in the course of forensic investigations. However, hairs that are naturally shed or that lack roots are problematic substrates for DNA profiling; these hair types often contain insufficient nuclear DNA to yield short tandem repeat (STR) profiles. Whilst there have been a number of initial investigations evaluating the value of metagenomics analyses for forensic applications (e.g. examination of computer keyboards), there have been no metagenomic evaluations of human hairs-a substrate commonly encountered during forensic practice. This present study attempts to address this forensic capability gap, by conducting a qualitative assessment into the applicability of metagenomic analyses of human scalp and pubic hair. Forty-two DNA extracts obtained from human scalp and pubic hairs generated a total of 79,766 reads, yielding 39,814 reads post control and abundance filtering. The results revealed the presence of unique combinations of microbial taxa that can enable discrimination between individuals and signature taxa indigenous to female pubic hairs. Microbial data from a single co-habiting couple added an extra dimension to the study by suggesting that metagenomic analyses might be of evidentiary value in sexual assault cases when other associative evidence is not present. Of all the data generated in this study, the next-generation sequencing (NGS) data generated from pubic hair held the most potential for forensic applications. Metagenomic analyses of human hairs may provide independent data to augment other forensic results and possibly provide association between victims of sexual assault and offender when other associative evidence is absent. Based on results garnered in the present study, we believe that with further development, bacterial profiling of hair will become a valuable addition to the forensic toolkit.

Is bilingualism associated with a lower risk of dementia in community-living older adults? Cross-sectional and prospective analyses.

PubMed

Yeung, Caleb M; St John, Philip D; Menec, Verena; Tyas, Suzanne L

2014-01-01

The aim of this study was to determine whether bilingualism is associated with dementia in cross-sectional or prospective analyses of older adults. In 1991, 1616 community-living older adults were assessed and were followed 5 years later. Measures included age, sex, education, subjective memory loss (SML), and the modified Mini-mental State Examination (3MS). Dementia was determined by clinical examination in those who scored below the cut point on the 3MS. Language status was categorized based upon self-report into 3 groups: English as a first language (monolingual English, bilingual English) and English as a Second Language (ESL). The ESL category had lower education, lower 3MS scores, more SML, and were more likely to be diagnosed with cognitive impairment, no dementia at both time 1 and time 2 compared with those speaking English as a first language. There was no association between being bilingual (ESL and bilingual English vs. monolingual) and having dementia at time 1 in bivariate or multivariate analyses. In those who were cognitively intact at time 1, there was no association between being bilingual and having dementia at time 2 in bivariate or multivariate analyses. We did not find any association between speaking >1 language and dementia.

Nurse staffing and patient outcomes in Belgian acute hospitals: cross-sectional analysis of administrative data.

PubMed

Van den Heede, Koen; Sermeus, Walter; Diya, Luwis; Clarke, Sean P; Lesaffre, Emmanuel; Vleugels, Arthur; Aiken, Linda H

2009-07-01

Studies have linked nurse staffing levels (number and skill mix) to several nurse-sensitive patient outcomes. However, evidence from European countries has been limited. This study examines the association between nurse staffing levels (i.e. acuity-adjusted Nursing Hours per Patient Day, the proportion of registered nurses with a Bachelor's degree) and 10 different patient outcomes potentially sensitive to nursing care. DESIGN-SETTING-PARTICIPANTS: Cross-sectional analyses of linked data from the Belgian Nursing Minimum Dataset (general acute care and intensive care nursing units: n=1403) and Belgian Hospital Discharge Dataset (general, orthopedic and vascular surgery patients: n=260,923) of the year 2003 from all acute hospitals (n=115). Logistic regression analyses, estimated by using a Generalized Estimation Equation Model, were used to study the association between nurse staffing and patient outcomes. The mean acuity-adjusted Nursing Hours per Patient Day in Belgian hospitals was 2.62 (S.D.=0.29). The variability in patient outcome rates between hospitals is considerable. The inter-quartile ranges for the 10 patient outcomes go from 0.35 for Deep Venous Thrombosis to 3.77 for failure-to-rescue. No significant association was found between the acuity-adjusted Nursing Hours per Patient Day, proportion of registered nurses with a Bachelor's degree and the selected patient outcomes. The absence of associations between hospital-level nurse staffing measures and patient outcomes should not be inferred as implying that nurse staffing does not have an impact on patient outcomes in Belgian hospitals. To better understand the dynamics of the nurse staffing and patient outcomes relationship in acute hospitals, further analyses (i.e. nursing unit level analyses) of these and other outcomes are recommended, in addition to inclusion of other study variables, including data about nursing practice environments in hospitals.

Metabolic Networks and Metabolites Underlie Associations Between Maternal Glucose During Pregnancy and Newborn Size at Birth

PubMed Central

Bain, James R.; Reisetter, Anna C.; Muehlbauer, Michael J.; Nodzenski, Michael; Stevens, Robert D.; Ilkayeva, Olga; Lowe, Lynn P.; Metzger, Boyd E.; Newgard, Christopher B.; Lowe, William L.

2016-01-01

Maternal metabolites and metabolic networks underlying associations between maternal glucose during pregnancy and newborn birth weight and adiposity demand fuller characterization. We performed targeted and nontargeted gas chromatography/mass spectrometry metabolomics on maternal serum collected at fasting and 1 h following glucose beverage consumption during an oral glucose tolerance test (OGTT) for 400 northern European mothers at ∼28 weeks' gestation in the Hyperglycemia and Adverse Pregnancy Outcome Study. Amino acids, fatty acids, acylcarnitines, and products of lipid metabolism decreased and triglycerides increased during the OGTT. Analyses of individual metabolites indicated limited maternal glucose associations at fasting, but broader associations, including amino acids, fatty acids, carbohydrates, and lipids, were found at 1 h. Network analyses modeling metabolite correlations provided context for individual metabolite associations and elucidated collective associations of multiple classes of metabolic fuels with newborn size and adiposity, including acylcarnitines, fatty acids, carbohydrates, and organic acids. Random forest analyses indicated an improved ability to predict newborn size outcomes by using maternal metabolomics data beyond traditional risk factors, including maternal glucose. Broad-scale association of fuel metabolites with maternal glucose is evident during pregnancy, with unique maternal metabolites potentially contributing specifically to newborn birth weight and adiposity. PMID:27207545

Factors associated with seasonal influenza vaccination in pregnant women.

PubMed

Henninger, Michelle L; Irving, Stephanie A; Thompson, Mark; Avalos, Lyndsay Ammon; Ball, Sarah W; Shifflett, Pat; Naleway, Allison L

2015-05-01

This observational study followed a cohort of pregnant women during the 2010-2011 influenza season to determine factors associated with vaccination. Participants were 1105 pregnant women who completed a survey assessing health beliefs related to vaccination upon enrollment and were then followed to determine vaccination status by the end of the 2010-2011 influenza season. We conducted univariate and multivariate analyses to explore factors associated with vaccination status and a factor analysis of survey items to identify health beliefs associated with vaccination. Sixty-three percent (n=701) of the participants were vaccinated. In the univariate analyses, multiple factors were associated with vaccination status, including maternal age, race, marital status, educational level, and gravidity. Factor analysis identified two health belief factors associated with vaccination: participant's positive views (factor 1) and negative views (factor 2) of influenza vaccination. In a multivariate logistic regression model, factor 1 was associated with increased likelihood of vaccination (adjusted odds ratio [aOR]=2.18; 95% confidence interval [CI]=1.72-2.78), whereas factor 2 was associated with decreased likelihood of vaccination (aOR=0.36; 95% CI=0.28-0.46). After controlling for the two health belief factors in multivariate analyses, demographic factors significant in univariate analyses were no longer significant. Women who received a provider recommendation were about three times more likely to be vaccinated (aOR=3.14; 95% CI=1.99-4.96). Pregnant women's health beliefs about vaccination appear to be more important than demographic and maternal factors previously associated with vaccination status. Provider recommendation remains one of the most critical factors influencing vaccination during pregnancy.

Maternal Smoking and the Risk of Cancer in Early Life - A Meta-Analysis.

PubMed

Rumrich, Isabell Katharina; Viluksela, Matti; Vähäkangas, Kirsi; Gissler, Mika; Surcel, Heljä-Marja; Hänninen, Otto

2016-01-01

In spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases. The aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations. In a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated. Smoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02-1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05-1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring. According to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies.

Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families

PubMed Central

Xu, X.-H.; Xiong, D.-H.; Liu, X.-G.; Guo, Y.; Chen, Y.; Zhao, J.; Recker, R. R.; Deng, H.-W.

2010-01-01

Summary This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. Introduction CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of ~44% found in this study), but the relevant genetic study is still rather scarce. Methods Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Results Significant associations with CSI were found with two SNPs (rs222029, P=0.0019; rs222020, P=0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Conclusions Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males. PMID:19543766

Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus

PubMed Central

Horne, Hisani N.; Chung, Charles C.; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Hopper, John L.; Southey, Melissa C.; Schmidt, Marjanka K.; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A.; Beckmann, Matthias W.; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J.; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L.; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K.; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V.; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H.; ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J.; Vachon, Celine; Giles, Graham G.; Milne, Roger L.; Haiman, Christopher A.; Marchand, Loic Le; Goldberg, Mark S.; Teo, Soo H.; Taib, Nur A. M.; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L.; Knight, Julia A.; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W. M.; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S.; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D. P.

2016-01-01

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799–121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000–120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08–1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive. PMID:27556229

Fine-Mapping of the 1p11.2 Breast Cancer Susceptibility Locus.

PubMed

Horne, Hisani N; Chung, Charles C; Zhang, Han; Yu, Kai; Prokunina-Olsson, Ludmila; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Fletcher, Olivia; Johnson, Nichola; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Benitez, Javier; González-Neira, Anna; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Khan, Sofia; Matsuo, Keitaro; Iwata, Hiroji; Dörk, Thilo; Bogdanova, Natalia V; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Chenevix-Trench, Georgia; Wu, Anna H; Ven den Berg, David; Smeets, Ann; Zhao, Hui; Chang-Claude, Jenny; Rudolph, Anja; Radice, Paolo; Barile, Monica; Couch, Fergus J; Vachon, Celine; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Marchand, Loic Le; Goldberg, Mark S; Teo, Soo H; Taib, Nur A M; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Shrubsole, Martha; Winqvist, Robert; Jukkola-Vuorinen, Arja; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; García-Closas, Montserrat; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; Martens, John W M; Li, Jingmei; Lu, Wei; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Shah, Mitul; Luccarini, Craig; Baynes, Caroline; Harrington, Patricia; Kang, Daehee; Choi, Ji-Yeob; Hartman, Mikael; Chia, Kee Seng; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Sangrajrang, Suleeporn; Brennan, Paul; Slager, Susan; Yannoukakos, Drakoulis; Shen, Chen-Yang; Hou, Ming-Feng; Swerdlow, Anthony; Orr, Nick; Simard, Jacques; Hall, Per; Pharoah, Paul D P; Easton, Douglas F; Chanock, Stephen J; Dunning, Alison M; Figueroa, Jonine D

2016-01-01

The Cancer Genetic Markers of Susceptibility genome-wide association study (GWAS) originally identified a single nucleotide polymorphism (SNP) rs11249433 at 1p11.2 associated with breast cancer risk. To fine-map this locus, we genotyped 92 SNPs in a 900kb region (120,505,799-121,481,132) flanking rs11249433 in 45,276 breast cancer cases and 48,998 controls of European, Asian and African ancestry from 50 studies in the Breast Cancer Association Consortium. Genotyping was done using iCOGS, a custom-built array. Due to the complicated nature of the region on chr1p11.2: 120,300,000-120,505,798, that lies near the centromere and contains seven duplicated genomic segments, we restricted analyses to 429 SNPs excluding the duplicated regions (42 genotyped and 387 imputed). Per-allelic associations with breast cancer risk were estimated using logistic regression models adjusting for study and ancestry-specific principal components. The strongest association observed was with the original identified index SNP rs11249433 (minor allele frequency (MAF) 0.402; per-allele odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.08-1.13, P = 1.49 x 10-21). The association for rs11249433 was limited to ER-positive breast cancers (test for heterogeneity P≤8.41 x 10-5). Additional analyses by other tumor characteristics showed stronger associations with moderately/well differentiated tumors and tumors of lobular histology. Although no significant eQTL associations were observed, in silico analyses showed that rs11249433 was located in a region that is likely a weak enhancer/promoter. Fine-mapping analysis of the 1p11.2 breast cancer susceptibility locus confirms this region to be limited to risk to cancers that are ER-positive.

Segregation of anterior temporal regions critical for retrieving names of unique and nonunique entities reflects underlying long-range connectivity

PubMed Central

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2015-01-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. PMID:26707082

Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption.

PubMed

Bergen, Andrew W; Michel, Martha; Nishita, Denise; Krasnow, Ruth; Javitz, Harold S; Conneely, Karen N; Lessov-Schlaggar, Christina N; Hops, Hyman; Zhu, Andy Z X; Baurley, James W; McClure, Jennifer B; Hall, Sharon M; Baker, Timothy B; Conti, David V; Benowitz, Neal L; Lerman, Caryn; Tyndale, Rachel F; Swan, Gary E

2015-01-01

The Nicotine Metabolite Ratio (NMR, ratio of trans-3'-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 PACT=4.1E-7, rs4803381 PACT=4.5E-5, rs1137115, PACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis.

Sex Hormones and Sleep in Men and Women From the General Population: A Cross-Sectional Observational Study.

PubMed

Kische, Hanna; Ewert, Ralf; Fietze, Ingo; Gross, Stefan; Wallaschofski, Henri; Völzke, Henry; Dörr, Marcus; Nauck, Matthias; Obst, Anne; Stubbe, Beate; Penzel, Thomas; Haring, Robin

2016-11-01

Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46-0.83), free T, and SHBG with AHI were rendered nonsignificant after multivariable adjustment. In multivariable analyses, ASD was associated with Epworth Sleepiness Scale (β-coefficient per SD increase in ASD: -0.71; 95% CI: -1.18 to -0.25). In women, multivariable analyses showed positive associations of dehydroepiandrosterone-sulphate with wake after sleep onset (β-coefficient: .16; 95% CI 0.03-0.28) and of E2 and E2 to TT ratio with Epworth Sleepiness Scale. Additionally, free T and SHBG were associated with AHI in multivariable models among premenopausal women. The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness. However, multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.

Genome-wide association and network analysis of lung function in the Framingham Heart Study.

PubMed

Liao, Shu-Yi; Lin, Xihong; Christiani, David C

2014-09-01

Single nucleotide polymorphisms have been found to be associated with pulmonary function using genome-wide association studies. However, lung function is a complex trait that is likely to be influenced by multiple gene-gene interactions besides individual genes. Our goal is to build a cellular network to explore the relationship between pulmonary function and genotypes by combining SNP level and network analyses using longitudinal lung function data from the Framingham Heart Study. We analyzed 2,698 genotyped participants from the Offspring cohort that had an average of 3.35 spirometry measurements per person for a mean length of 13 years. Repeated forced expiratory volume in one second (FEV1 ) and the ratio of FEV1 to forced vital capacity (FVC) were used as outcomes. Data were analyzed using linear-mixed models for the association between lung function and alleles by accounting for the correlation among repeated measures over time within the same subject and within-family correlation. Network analyses were performed using dmGWAS and validated with data from the Third Generation cohort. Analyses identified SMAD3, TGFBR2, CD44, CTGF, VCAN, CTNNB1, SCGB1A1, PDE4D, NRG1, EPHB1, and LYN as contributors to pulmonary function. Most of these genes were novel that were not found previously using solely SNP-level analysis. These novel genes are involving the transforming growth factor beta (TGFB)-SMAD pathway, Wnt/beta-catenin pathway, etc. Therefore, combining SNP-level and network analyses using longitudinal lung function data is a useful alternative strategy to identify risk genes. © 2014 WILEY PERIODICALS, INC.

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis

PubMed Central

Smith, J. Gustav; Almgren, Peter; Engström, Gunnar; Hedblad, Bo; Platonov, Pyotr G.; Newton-Cheh, Christopher; Melander, Olle

2013-01-01

Objectives Genome-wide association studies have recently identified genetic polymorphisms associated with common, etiologically complex diseases, for which direct-to-consumer genetic testing with provision of absolute genetic risk estimates is marketed by commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates but the robustness of such estimates across populations and study designs has not been studied. Design A systematic literature review with meta-analysis and assessment of between-study heterogeneity was performed for single nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. Results Data from 18 samples of European ancestry (n=12,100 cases; 115,702 controls) were identified for the SNP on chromosome 4q25 (rs220733), 16 samples (n=12,694 cases; 132,602 controls) for the SNP on 16q22 (rs2106261) and 4 samples (n=5,272 cases; 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the discovery studies were identified for SNPs on 1q21 and in GJA5 and IL6R, why no meta-analyses were performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs from genome-wide studies on 4q25 (OR 1.67, 95% CI=1.50–1.86, p=2×10−21) and 16q22 (OR 1.21, 95% CI=1.13–1.29, p=1×10−8), but not the SNP in KCNH2 from candidate gene studies (p=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I2=0.50–0.78, p<0.05), but not across prospective cohort studies (I2=0.39, p=0.15). Both polymorphisms were robustly associated with AF for each study design individually (p<0.05). Conclusions In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates. PMID:22690879

Analysis of audiometric notch as a noise-induced hearing loss phenotype in US youth: data from the National Health And Nutrition Examination Survey, 2005-2010.

PubMed

Bhatt, Ishan S; Guthrie, O'neil

2017-06-01

Bilateral audiometric notch (BN) at 4000-6000 Hz was identified as a noise-induced hearing loss (NIHL) phenotype for genetic association analysis in college-aged musicians. This study analysed BN in a sample of US youth. Prevalence of the BN within the study sample was determined and logistic-regression analyses were performed to identify audiologic and other demographic factors associated with BN. Computer-simulated "flat" audiograms were used to estimate potential influence of false-positive rates in estimating the prevalence of the BN. 2348 participants (12-19 years) following the inclusion criteria were selected from the National Health and Nutrition Examination Survey data (2005-2010). The prevalence of BN was 16.6%. Almost 55.6% of the participants showed notch in at least one ear. Noise exposure, gender, ethnicity and age showed significant relationship with the BN. Computer simulation revealed that 5.5% of simulated participants with "flat" audiograms showed BN. Association of noise exposure with BN suggests that it is a useful NIHL phenotype for genetic association analyses. However, further research is necessary to reduce false-positive rates in notch identification.

Body Mass Index (BMI) Is Associated with Microalbuminuria in Chinese Hypertensive Patients

PubMed Central

Liu, Xinyu; Liu, Yu; Chen, Youming; Li, Yongqiang; Shao, Xiaofei; Liang, Yan; Li, Bin; Holthöfer, Harry; Zhang, Guanjing; Zou, Hequn

2015-01-01

There is no general consensus on possible factors associated with microalbuminuria in hypertensive patients nor any reported study about this issue in Chinese patients. To examine this issues, 944 hypertensive patients were enrolled in a study based on a cross-sectional survey conducted in Southern China. Multivariate regression analyses were performed to identify the factors related with the presence of microalbuminuria and urinary excretion of albumin. The prevalence of microalbuminuria in hypertensive and non-diabetic hypertensive patients were 17.16% and 15.25%, respectively. Body mass index (BMI), but not waist circumference (WC), were independently associated with microalbuminuria and the values of urinary albumin to creatinine ratio (ACR) based on multiple regression analyses, even after excluding diabetic patients and patients taking inhibitors of the renin-angiotensin system from the analyses. Furthermore, patients with obesity (BMI ≥28) had higher levels of ACR, compared with those with normal weight (BMI <24 kg/m2) and overweight (24 kg/m2≤ BMI < 28). In conclusion, BMI, as a modifiable factor, is closely associated with microalbuminuria among Chinese hypertensive patients, which may provide a basis for future development of intervention approaches for these patients. PMID:25674785

Distinct Functional Networks Associated with Improvement of Affective Symptoms and Cognitive Function During Citalopram Treatment in Geriatric Depression

PubMed Central

Diaconescu, Andreea Oliviana; Kramer, Elisse; Hermann, Carol; Ma, Yilong; Dhawan, Vijay; Chaly, Thomas; Eidelberg, David; McIntosh, Anthony Randal; Smith, Gwenn S.

2010-01-01

Variability in the affective and cognitive symptom response to antidepressant treatment has been observed in geriatric depression. The underlying neural circuitry is poorly understood. The current study evaluated the cerebral glucose metabolic effects of citalopram treatment and applied multivariate, functional connectivity analyses to identify brain networks associated with improvements in affective symptoms and cognitive function. Sixteen geriatric depressed patients underwent resting Positron Emission Tomography (PET) studies of cerebral glucose metabolism and assessment of affective symptoms and cognitive function before and after eight weeks of selective serotonin reuptake inhibitor treatment (citalopram). Voxel-wise analyses of the normalized glucose metabolic data showed decreased cerebral metabolism during citalopram treatment in the anterior cingulate gyrus, middle temporal gyrus, precuneus, amygdala, and parahippocampal gyrus. Increased metabolism was observed in the putamen, occipital cortex and cerebellum. Functional connectivity analyses revealed two networks which were uniquely associated with improvement of affective symptoms and cognitive function during treatment. A subcortical-limbic-frontal network was associated with improvement in affect (depression and anxiety), while a medial temporal-parietal-frontal network was associated with improvement in cognition (immediate verbal learning/memory and verbal fluency). The regions that comprise the cognitive network overlap with the regions that are affected in Alzheimer’s dementia. Thus, alterations in specific brain networks associated with improvement of affective symptoms and cognitive function are observed during citalopram treatment in geriatric depression. PMID:20886575

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

PubMed

Laursen, S B; Leontiadis, G I; Stanley, A J; Hallas, J; Schaffalitzky de Muckadell, O B

2017-08-01

Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding. © 2017 John Wiley & Sons Ltd.

[Association between radiation from mobile phones and tumour risk in adults].

PubMed

Bielsa-Fernández, Patricia; Rodríguez-Martín, Beatriz

To synthesize and analyse systematic reviews, case-control studies, cohort studies and meta-analysis that investigate the association between exposure to radiofrequency from mobile phones and the appearance of tumours in adults. A systematic search was conducted in Scopus, Web of Science, The Cochrane Library, Medline and Cinahl of articles published in English and Spanish between January 2005 and February 2016 that analyse the risk of tumour associated with exposure to radiofrequency from mobile phones in adults. The recommendations of the PRISMA Declaration were followed, and the quality of the articles was analysed with the AMSTAR tool and the Newcastle-Ottawa Scale. 1034 studies were found, fourteen of which were included. Most studies agree that it is not possible to determine a relationship in the short term, although long-term (over 10 years) radiofrequency emitted by mobile phones can cause tumour effects, with an increased risk by ipsilateral exposure and latency. Although radiofrequency from mobile phones has tumour effects on humans, the available scientific evidence is not robust. More rigorous follow-up studies with larger sample sizes and broader periods are necessary to learn more about the long-term effects. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Thai Adolescent Survivors 1 Year after the 2004 Tsunami: A Mixed Methods Study

ERIC Educational Resources Information Center

Tuicomepee, Arunya; Romano, John L.

2008-01-01

This study examined the impact of the 2004 Asian tsunami on 400 Thai adolescents 1 year after the disaster. Quantitative analyses showed that youth behavior problems were positively associated with tsunami experiences and negatively associated with positive family functioning. Tsunami exposure, school connectedness, religious beliefs and…

Survey of New Horizons International Music Association Musicians

ERIC Educational Resources Information Center

Coffman, Don

2009-01-01

This study analysed survey responses from 1652 New Horizons International Music Association (NHIMA) musicians in the United States and Canada to better understand older adults' experiences in making music. The purpose of this study was threefold: (a) ascertain the extent of NHIMA musicians' musical backgrounds and their current involvement in…

Association of HLA-DQA1 and -DQB1 alleles with type I diabetes in Arabs: a meta-analyses.

PubMed

Hamzeh, A R; Nair, P; Al-Khaja, N; Al Ali, M T

2015-07-01

This study aimed at assessing the nature and significance of associations between various alleles of HLA-DQA1, HLA-DQB1, and type I diabetes (T1D) in Arab populations. Evidence from literature (published before 20 April 2015) was amassed and analysed through multiple meta-analyses, which yielded effect summary odds ratios and 95% confidence intervals for 24 alleles and 4 haplotypes. A total of 1273 cases and 1747 controls from 16 studies were analysed. High levels of significance were obtained to support higher T1D risk when harbouring DQA1*03:01. The alleles DQB1*02:01 and *03:02 and the haplotypes DR3 and DR4 were significant risk factors, albeit with high publication heterogeneity. The protective effects of DQA1*01:01, DQB1*05:03, *06:02, *06:03, and *06:04 were robustly suggested by all indicators of meta-analyses. The haplotypes DR7 and DR11 were strongly suggested to be protective in Arabs. A relatively small number of studies have emerged from Arab countries, mostly with inadequate power on an individual basis. This study fills the gap by providing significant size effect of human leukocyte antigen (HLA) alleles and completes the continuum of global ethnic differences in this context. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between Elder Abuse and Metabolic Syndromes: Findings from the Chicago Health and Aging Project.

PubMed

Dong, XinQi; Simon, Melissa

2015-01-01

Elder abuse and metabolic syndromes are both important public health issues and are associated with increased morbidity and mortality. This study aimed to examine the associations between elder abuse and risk for metabolic syndromes. The Chicago Health and Aging Project (CHAP) cohort is a population-based study (n = 4,586). We identified 676 participants with some form of elder abuse reported to a social services agency. The primary independent variable was elder abuse reported to a social services agency. Outcomes were metabolic syndrome as categorized by World Health Organization (WHO), American Heart Association (AHA) and International Diabetes Federation (IDF) criteria. Bivariate and logistic regression analyses were used to assess the association between elder abuse and different definitions of metabolic syndromes. In the bivariate analyses, elder abuse victims were more likely than those without elder abuse to have metabolic syndromes [22.4 vs. 10.7% (WHO), 50.7 vs. 40.0% (AHA) and 47.7 vs. 33.5% (IDF)]. After adjusting for potential confounding factors, elder abuse was associated with an increased risk for metabolic syndromes according to WHO [OR, 3.95 (2.86-5.47)], AHA [OR, 2.03 (1.56-2.64)] and IDF [OR, 2.55 (1.97-3.29)] criteria. Interaction term analyses indicate that the association between elder abuse and metabolic syndromes may be moderated by sociodemographic characteristics but not by health-related or psychosocial factors. Elder abuse is associated with an increased risk for metabolic syndromes. Research is needed to examine the association between elder abuse and cardiovascular disease.

Association Between Elder Abuse and Metabolic Syndromes: Findings from the Chicago Health and Aging Project

PubMed Central

Dong, XinQi; Simon, Melissa

2014-01-01

Background Elder abuse and metabolic syndromes are both important public health issues and are associated with increased morbidity and mortality. This study aimed to examine the associations between elder abuse and risk for metabolic syndromes. Methods Chicago Health and Aging Project (CHAP) cohort is a population-based study (N=4,586). We identified 676 participants with some form of elder abuse reported to a social services agency. The primary independent variable was elder abuse reported to a social services agency. Outcomes were metabolic syndrome as categorized by World Health Organization (WHO), American Heart Association (AHA) and International Diabetes Federation (IDF) criteria. Bivariate and logistic regression analyses were used to assess the association between elder abuse and different definitions of metabolic syndromes. Results In the bivariate analyses, elder abuse victims were more likely than those without elder abuse to have metabolic syndromes (22.4% vs. 10.7% [WHO], 50.7% vs. 40.0% [AHA], and 47.7% vs. 33.5% [IDF]). After adjusting for potential confounding factors, elder abuse was associated with increased risk for metabolic syndromes according to WHO (OR, 3.95 (2.86-5.47), AHA (OR, 2.03 (1.56-2.64) and IDF (OR, 2.55 (1.97-3.29) criteria. Interaction term analyses indicate that the association between elder abuse and metabolic syndromes may be moderated by sociodemographic characteristics, but not by health related or psychosocial factors. Conclusion Elder abuse is associated with increased risk for metabolic syndromes. Research is needed to examine the association between elder abuse and cardiovascular disease. PMID:25471532

No association between hair cortisol or cortisone and brain morphology in children.

PubMed

Chen, Ruoqing; Muetzel, Ryan L; El Marroun, Hanan; Noppe, Gerard; van Rossum, Elisabeth F C; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Fang, Fang; Tiemeier, Henning

2016-12-01

Little is known about the relationship between the long-term hypothalamic-pituitary-adrenal (HPA) axis functioning and brain structure in children. Glucocorticoid in hair has emerged as an important biomarker of HPA activity. In this study, we investigated the associations of hair cortisol and cortisone concentrations with brain morphology in young children. We included 219 children aged 6-10 years from the Generation R Study in Rotterdam, the Netherlands. We examined cortisol and cortisone concentrations by hair analysis using liquid chromatography-tandem mass spectrometry, and assessed brain morphometric measures with structural magnetic resonance imaging. The relationships of hair cortisol and cortisone concentrations with brain volumetrics, cortical thickness, cortical surface area and gyrification were analyzed separately after adjustment for several potential confounding factors. We observed a positive association between cortisol concentrations and cortical surface area in the parietal lobe, positive associations of cortisone concentrations with thalamus volume, occipital lobe volume and cortical surface area in the parietal lobe, and a negative association between cortisone concentrations and cortical surface area in the temporal lobe in the regions of interest analyses. A negative association between cortisol or cortisone concentrations and hippocampal volume was observed in children with behavioral problems. The whole brain vertex-wise analyses did however not show any association between cortisol or cortisone concentration and brain morphometric measures after correction for multiple testing. Although some associations are noted in region of interest analyses, we do not observe clear association of hair cortisol or cortisone with brain morphometric measures in typically developing young children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bioinformatic analyses to select phenotype affecting polymorphisms in HTR2C gene.

PubMed

Piva, Francesco; Giulietti, Matteo; Baldelli, Luisa; Nardi, Bernardo; Bellantuono, Cesario; Armeni, Tatiana; Saccucci, Franca; Principato, Giovanni

2011-08-01

Single nucleotide polymorphisms (SNPs) in serotonin related genes influence mental disorders, responses to pharmacological and psychotherapeutic treatments. In planning association studies, researchers that want to investigate new SNPs have to select some among a large number of candidates. Our aim is to guide researchers in the selection of the most likely phenotype affecting polymorphisms. Here, we studied serotonin receptor 2C (HTR2C) SNPs because, till now, only relatively few of about 2000 are investigated. We used the most updated and assessed bioinformatic tools to predict which variations can give rise to biological effects among 2450 HTR2C SNPs. We suggest 48 SNPs that are worth considering in future association studies in the field of psychiatry, psychology and pharmacogenomics. Moreover, our analyses point out the biological level probably affected, such as transcription, splicing, miRNA regulation and protein structure, thus allowing to suggest future molecular investigations. Although few association studies are available in literature, their results are in agreement with our predictions, showing that our selection methods can help to guide future association studies. Copyright © 2011 John Wiley & Sons, Ltd.

Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry

PubMed Central

Iqbal, M. Bilal; Robinson, Simon D.; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W.; Hodge, Steven; Della Siega, Anthony; Nadra, Imad J.

2016-01-01

Background Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non-randomized studies may remain biased. Methods We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008–2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. Results A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20–2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84–1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Δ = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non-diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. Conclusions In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data. PMID:26870950

Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses

PubMed Central

Kogelman, Lisette J. A.; Pant, Sameer D.; Fredholm, Merete; Kadarmideen, Haja N.

2014-01-01

Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie it. PMID:25071839

[Association of XRCC1 genetic polymorphism with susceptibility to non-Hodgkin's lymphoma].

PubMed

Li, Su-Xia; Zhu, Hong-Li; Guo, Bo; Yang, Yang; Wang, Hong-Yan; Sun, Jing-Fen; Cao, Yong-Bin

2014-08-01

The purpose of this study was to explore the association between X-ray repair cross-complementing group 1 (XRCC1)gene polymorphism and non-Hodgkin's lymphoma risk. A total of 282 non-Hodgkin's lymphoma (NHL) patients and 231 normal controls were used to investigate the effect of three XRCC1 gene polymorphisms (rs25487, rs25489, rs1799782) on susceptibility to non-Hodgkin's lymphoma. Genotyping was performed by using SNaPshot method. All statistical analyses were done with R software. Genotype and allele frequencies of XRCC1 were compared between the patients and controls by using the chi-square test. Crude and adjusted odd ratios and 95% confidence intervals were calculated by using logistic regression on the basis of genetic different models. For four kinds of NHL, subgroup analyses were also conducted. Combined genotype analyses of the three XRCC1 polymorphisms were also done by using logistic regression. The results showed that the variant genotype frequency was not significantly different between the controls and NHL or NHL subtype cases. Combined genotype analyses of XRCC1 399-280-194 results showed that the combined genotype was not associated with risk of NHL overall, but the VT-WT-WT combined genotype was associated with the decreased risk of T-NHL (OR: 0.21; 95%CI (0.06-0.8); P = 0.022), and the WT-VT-WT combined genotype was associated with the increased risk of FL(OR:15.23; 95%CI (1.69-137.39); P = 0.015). It is concluded that any studied polymorphism (rs25487, rs25489, rs1799782) alone was not shown to be rela-ted with the risk of NHL or each histologic subtype of NHL. The combined genotype with mutation of three SNP of XRCC1 was not related to the risk of NHL. However, further large-scale studies would be needed to confirm the association of decreased or increased risk for T-NHL and FL with the risk 3 combined SNP mutants of XRCC1 polymorphism.

Long-Term Coffee Consumption Is Associated with Decreased Incidence of New-Onset Hypertension: A Dose-Response Meta-Analysis.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Pajak, Andrzej; Sciacca, Salvatore; Bes-Rastrollo, Maira; Galvano, Fabio; Martinez-Gonzalez, Miguel A

2017-08-17

To perform a dose-response meta-analysis of prospective cohort studies investigating the association between long-term coffee intake and risk of hypertension. An online systematic search of studies published up to November 2016 was performed. Linear and non-linear dose-response meta-analyses were conducted; potential evidence of heterogeneity, publication bias, and confounding effect of selected variables were investigated through sensitivity and meta-regression analyses. Seven cohorts including 205,349 individuals and 44,120 cases of hypertension were included. In the non-linear analysis, there was a 9% significant decreased risk of hypertension per seven cups of coffee a day, while, in the linear dose-response association, there was a 1% decreased risk of hypertension for each additional cup of coffee per day. Among subgroups, there were significant inverse associations for females, caffeinated coffee, and studies conducted in the US with longer follow-up. Analysis of potential confounders revealed that smoking-related variables weakened the strength of association between coffee consumption and risk of hypertension. Increased coffee consumption is associated with a modest decrease in risk of hypertension in prospective cohort studies. Smoking status is a potential effect modifier on the association between coffee consumption and risk of hypertension.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study.

PubMed

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Godet, Thomas; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Blanchon, Loic; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

2018-01-01

Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536.

Whole genome sequence analyses of brain imaging measures in the Framingham Study.

PubMed

Sarnowski, Chloé; Satizabal, Claudia L; DeCarli, Charles; Pitsillides, Achilleas N; Cupples, L Adrienne; Vasan, Ramachandran S; Wilson, James G; Bis, Joshua C; Fornage, Myriam; Beiser, Alexa S; DeStefano, Anita L; Dupuis, Josée; Seshadri, Sudha

2018-01-16

We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program. We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants. We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10 -8 ) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10 -8 ). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10 -4 ) and in 17q25 for WMH (rs7214628, p = 2.0 × 10 -3 ) were confirmed. Gene-based tests detected associations ( p ≤ 2.3 × 10 -6 ) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- ( UNC5D ) and Parkinson disease-associated genes ( GBA ). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways. Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

PubMed

Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

2017-06-01

Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

Revisiting the Antecedents of Social Entrepreneurial Intentions in Hong Kong

ERIC Educational Resources Information Center

Ip, Ching Yin; Wu, Shih-Chia; Liu, Huei-Ching; Liang, Chaoyun

2017-01-01

This study examined how empathy, moral obligation, social entrepreneurial self-efficacy, perceived social support, and prior experience with social problems are associated with social entrepreneurial intentions. Through a survey, a sample of 252 Hong Kong students was used for analyses. Factor analyses supported that the antecedents of social…

A Systematic Review of the Relationships between Intimate Partner Violence and HIV/AIDS

PubMed Central

Kouyoumdjian, Fiona G.; Findlay, Nicole; Schwandt, Michael; Calzavara, Liviana M.

2013-01-01

Background Intimate partner violence (IPV) is a significant health problem that has been associated with HIV infection in numerous studies. We aimed to systematically review the literature on relationships between IPV and HIV in order to describe the prevalence of IPV in people with HIV, the prevalence of HIV in people experiencing IPV, the association between IPV and HIV, and evidence regarding mechanisms of risk and interventions. Methods Data sources were 10 electronic databases and reference lists. Studies were included if they reported data on the relationship between IPV and HIV. All records were independently reviewed by two authors at the stages of title and abstract review and full text review. Any abstract considered eligible by either reviewer was reviewed in full, and any disagreement regarding eligibility of full texts or data extracted was resolved by discussion. Results 101 articles were included. Experiencing IPV and HIV infection were associated in unadjusted analyses in most studies, as well as in adjusted analyses in many studies. The findings of qualitative and quantitative studies assessing potential mechanisms linking IPV and HIV were variable. Few interventions have been assessed, but two identified in this review were promising in terms of preventing IPV, though not HIV infection. Conclusions Experiencing IPV and HIV infection tend to be associated in unadjusted analyses, suggesting that IPV screening and linkage with relevant programs and services may be valuable. It is unclear whether there is a causal association between experiencing IPV and HIV infection. Research should focus on defining parameters of IPV which are relevant to HIV infection, including type of IPV and period of exposure and risk, on assessing potential mechanisms, and on developing and assessing interventions which build on the strengths of existing studies. PMID:24282566

Emotional support, education and self-rated health in 22 European countries.

PubMed

von dem Knesebeck, Olaf; Geyer, Siegfried

2007-10-01

The analyses focus on three aims: (1) to explore the associations between education and emotional support in 22 European countries, (2) to explore the associations between emotional support and self-rated health in the European countries, and (3) to analyse whether the association between education and self-rated health can be partly explained by emotional support. The study uses data from the European Social Survey 2003. Probability sampling from all private residents aged 15 years and older was applied in all countries. The European Social Survey includes 42,359 cases. Persons under age 25 were excluded to minimise the number of respondents whose education was not complete. Education was coded according to the International Standard Classification of Education. Perceived emotional support was assessed by the availability of a confidant with whom one can discuss intimate and personal matters with. Self-rated health was used as health indicator. Results of multiple logistic regression analyses show that emotional support is positively associated with education among women and men in most European countries. However, the magnitude of the association varies according to country and gender. Emotional support is positively associated with self-rated health. Again, gender and country differences in the association were observed. Emotional support explains little of the educational differences in self-rated health among women and men in most European countries. Results indicate that it is important to consider socio-economic factors like education and country-specific contexts in studies on health effects of emotional support.

The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-Analysis Revisited: Evidence of Genetic Moderation

PubMed Central

Karg, Katja; Burmeister, Margit; Shedden, Kerby; Sen, Srijan

2013-01-01

Context The initial report of an interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression is perhaps the best-known and most cited finding in psychiatric genetics. Two recent meta-analyses explored the studies seeking to replicate this initial report and concluded that the evidence did not support the presence of the interaction. However, even the larger of the meta-analyses included only 14 of the 56 studies that have explored the relationship between 5-HTTLPR, stress and depression. Objective We sought to perform a meta-analysis including all relevant studies assessing whether 5-HTTLPR moderates the relationship between stress and depression. Data Sources We identified relevant articles from previous meta-analyses and reviews and a PubMed database search. Study Selection We excluded two studies presenting data that were included in other, larger, studies already included in our meta-analysis to avoid duplicate counting of subjects. Data Extraction In order to perform a more inclusive meta-analysis, we used the Liptak-Stouffer Z-score method to combine findings of primary studies at the significance test level rather than raw data level. Results We included 54 studies and found strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the 5-HTTLPR s allele associated with an increased risk of developing depression under stress (p<0.0001). When restricting our analysis to the studies included in the previous meta-analyses, we found no evidence of association (Munafo studies p=0.16; Risch studies p=0.11). This suggests that the difference in results between previous meta-analyses and ours was not due to the difference in meta-analytic technique but instead to the expanded set of studies included in this analysis. Conclusions Contrary to the results of the smaller earlier meta-analyses, we find strong evidence that 5-HTTLPR moderates the relationship between stress and depression in the studies published to date. PMID:21199959

Comparison of Anticipation and Study-Test Procedures of Paired-Associate Learning by Children. Final Report.

ERIC Educational Resources Information Center

Cole, Lawrence E.

The study paired-associate (PA) learning via the anticipation (ANT) and study-test (ST) procedures across second, third, fourth and fifth grades. Specifically, age differences in the rate of learning and examining PA learning according to the stage analyses were examined. Retention was also of interest: however, a ceiling effect negated the…

Contour plot assessment of existing meta-analyses confirms robust association of statin use and acute kidney injury risk.

PubMed

Chevance, Aurélie; Schuster, Tibor; Steele, Russell; Ternès, Nils; Platt, Robert W

2015-10-01

Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure. The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary fiber intake reduces risk for Barrett's esophagus and esophageal cancer.

PubMed

Sun, Lingli; Zhang, Zhizhong; Xu, Jian; Xu, Gelin; Liu, Xinfeng

2017-09-02

Observational studies suggest an association between dietary fiber intake and risk of Barrett's esophagus and esophageal cancer. However, the results are inconsistent. To conduct a meta-analysis of observational studies to assess this association. All eligible studies were identified by electronic searches in PubMed and Embase through February 2015. Dose-response, subgroup, sensitivity, and publication bias analyses were performed. A total of 15 studies involving 16,885 subjects were included in the meta-analysis. The pooled odds ratio for the highest compared with the lowest dietary fiber intake was 0.52 (95% CI, 0.43-0.64). Stratified analyses for tumor subtype, study design, geographic location, fiber type, publication year, total sample size, and quality score yielded consistent results. Dose-response analysis indicated that a 10-g/d increment in dietary fiber intake was associated with a 31% reduction in Barrett's esophagus and esophageal cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the overall risk estimate. Our findings indicate that dietary fiber intake is inversely associated with risk of Barrett's esophagus and esophageal cancer. Further large prospective studies are warranted.

Anthropometric measurements and periodontal diseases in children and adolescents: a systematic review and meta-analysis.

PubMed

Li, Ling-Wei; Wong, Hai Ming; Sun, Ling; Wen, Yi Feng; McGrath, Colman P

2015-11-01

The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2-18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: -0.89; 95% CI: -1.18, -0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended. © 2015 American Society for Nutrition.

Anthropometric Measurements and Periodontal Diseases in Children and Adolescents: A Systematic Review and Meta-Analysis123

PubMed Central

Li, Ling-Wei; Wong, Hai Ming; Sun, Ling; Wen, Yi Feng; McGrath, Colman P

2015-01-01

The aim of this systematic review was to identify and summarize evidence of the association between anthropometric measurements and periodontal status in children and adolescents. We searched PubMed, Institute for Scientific Information Web of Knowledge, Cochrane Library, and 7 additional databases, following the guidance of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, up to December 2014. Observational studies reporting data on the association between anthropometric measurements and periodontal diseases in 2–18-y-old participants were included. An initial search identified 4191 papers; 278 potentially effective studies (k = 0.82) and 16 effective studies (k = 0.83) were included after screening. The mean quality of evidence among the studies was 20.3, according to the Strengthening the Reporting of Observational studies in Epidemiology checklist (k = 0.79). Meta-analyses showed that obesity (measured by body mass index) was significantly associated with visible plaque index (OR: 4.75; 95% CI: 2.42, 9.34), bleeding on probing (OR: 5.41; 95% CI: 2.75, 10.63), subgingival calculus (OR: 3.07; 95% CI: 1.10, 8.62), probing depth (OR: 14.15; 95% CI: 5.10, 39.25) and flow rate of salivary secretion (standardized mean difference: −0.89; 95% CI: −1.18, −0.61). However, various results were reported in the effective studies that were not included in meta-analyses. In conclusion, obesity is associated with some signs of periodontal disease in children and adolescents. Further studies with a comprehensive prospective cohort design and more potential variables are recommended. PMID:26567204

The Association Between Health Program Participation and Employee Retention.

PubMed

Mitchell, Rebecca J; Ozminkowski, Ronald J; Hartley, Stephen K

2016-09-01

Using health plan membership as a proxy for employee retention, the objective of this study was to examine whether use of health promotion programs was associated with employee retention. Propensity score weighted generalized linear regression models were used to estimate the association between telephonic programs or health risk surveys and retention. Analyses were conducted with six study samples based on type of program participation. Retention rates were highest for employees with either telephonic program activity or health risk surveys and lowest for employees who did not participate in any interventions. Participants ranged from 71% more likely to 5% less likely to remain with their employers compared with nonparticipants, depending on the sample used in analyses. Using health promotion programs in combination with health risk surveys may lead to improvements in employee retention.

Chemistry of precipitation, streamwater, and lakewater from the Hubbard Brook Ecosystem Study: a record of sampling protocols and analytical procedures

Treesearch

Donald C. Buso; Gene E. Likens; John S. Eaton

2000-01-01

The Hubbard Brook Ecosystem Study (HBES), begun in 1963, is a long-term effort to understand the structure, function and change in forest watersheds and associated aquatic ecosystems at the Hubbard Brook Experimental Forest in New Hampshire. Chemical analyses of streamwater and precipitation collections began in 1963, and analyses of lakewater collections began in 1967...

Pleiotropic and Sex-Specific Effects of Cancer GWAS SNPs on Melanoma Risk in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

PubMed Central

Kocarnik, Jonathan M.; Park, S. Lani; Han, Jiali; Dumitrescu, Logan; Cheng, Iona; Wilkens, Lynne R.; Schumacher, Fredrick R.; Kolonel, Laurence; Carlson, Chris S.; Crawford, Dana C.; Goodloe, Robert J.; Dilks, Holli H.; Baker, Paxton; Richardson, Danielle; Matise, Tara C.; Ambite, José Luis; Song, Fengju; Qureshi, Abrar A.; Zhang, Mingfeng; Duggan, David; Hutter, Carolyn; Hindorff, Lucia; Bush, William S.; Kooperberg, Charles; Le Marchand, Loic; Peters, Ulrike

2015-01-01

Background Several regions of the genome show pleiotropic associations with multiple cancers. We sought to evaluate whether 181 single-nucleotide polymorphisms previously associated with various cancers in genome-wide association studies were also associated with melanoma risk. Methods We evaluated 2,131 melanoma cases and 20,353 controls from three studies in the Population Architecture using Genomics and Epidemiology (PAGE) study (EAGLE-BioVU, MEC, WHI) and two collaborating studies (HPFS, NHS). Overall and sex-stratified analyses were performed across studies. Results We observed statistically significant associations with melanoma for two lung cancer SNPs in the TERT-CLPTM1L locus (Bonferroni-corrected p<2.8x10-4), replicating known pleiotropic effects at this locus. In sex-stratified analyses, we also observed a potential male-specific association between prostate cancer risk variant rs12418451 and melanoma risk (OR=1.22, p=8.0x10-4). No other variants in our study were associated with melanoma after multiple comparisons adjustment (p>2.8e-4). Conclusions We provide confirmatory evidence of pleiotropic associations with melanoma for two SNPs previously associated with lung cancer, and provide suggestive evidence for a male-specific association with melanoma for prostate cancer variant rs12418451. This SNP is located near TPCN2, an ion transport gene containing SNPs which have been previously associated with hair pigmentation but not melanoma risk. Previous evidence provides biological plausibility for this association, and suggests a complex interplay between ion transport, pigmentation, and melanoma risk that may vary by sex. If confirmed, these pleiotropic relationships may help elucidate shared molecular pathways between cancers and related phenotypes. PMID:25789475

Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder.

PubMed

Navarro-Mateu, Fernando; Escámez, Teresa; Koenen, Karestan C; Alonso, Jordi; Sánchez-Meca, Julio

2013-01-01

To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.

Methodological Standards for Meta-Analyses and Qualitative Systematic Reviews of Cardiac Prevention and Treatment Studies: A Scientific Statement From the American Heart Association.

PubMed

Rao, Goutham; Lopez-Jimenez, Francisco; Boyd, Jack; D'Amico, Frank; Durant, Nefertiti H; Hlatky, Mark A; Howard, George; Kirley, Katherine; Masi, Christopher; Powell-Wiley, Tiffany M; Solomonides, Anthony E; West, Colin P; Wessel, Jennifer

2017-09-05

Meta-analyses are becoming increasingly popular, especially in the fields of cardiovascular disease prevention and treatment. They are often considered to be a reliable source of evidence for making healthcare decisions. Unfortunately, problems among meta-analyses such as the misapplication and misinterpretation of statistical methods and tests are long-standing and widespread. The purposes of this statement are to review key steps in the development of a meta-analysis and to provide recommendations that will be useful for carrying out meta-analyses and for readers and journal editors, who must interpret the findings and gauge methodological quality. To make the statement practical and accessible, detailed descriptions of statistical methods have been omitted. Based on a survey of cardiovascular meta-analyses, published literature on methodology, expert consultation, and consensus among the writing group, key recommendations are provided. Recommendations reinforce several current practices, including protocol registration; comprehensive search strategies; methods for data extraction and abstraction; methods for identifying, measuring, and dealing with heterogeneity; and statistical methods for pooling results. Other practices should be discontinued, including the use of levels of evidence and evidence hierarchies to gauge the value and impact of different study designs (including meta-analyses) and the use of structured tools to assess the quality of studies to be included in a meta-analysis. We also recommend choosing a pooling model for conventional meta-analyses (fixed effect or random effects) on the basis of clinical and methodological similarities among studies to be included, rather than the results of a test for statistical heterogeneity. © 2017 American Heart Association, Inc.

The link between discrimination and telomere length in African American adults.

PubMed

Lee, Daniel B; Kim, Eric S; Neblett, Enrique W

2017-05-01

Prior work shows that discrimination is associated with a wide array of negative health outcomes. However, the biological mechanisms through which this link occurs require more study. We evaluated the association between discrimination and leukocyte telomere length (LTL; a biological marker of systemic aging). Cross-sectional data were from the Health and Retirement study, a study of people aged 51+ in the United States, and included 595 African American males and females. Multiple regression analyses were used to evaluate whether discrimination was independently associated with LTL. We also considered the role of potential confounders including sociodemographic factors, health factors, depressive symptoms, and stress. High discrimination was associated with shorter LTL after controlling for sociodemographic factors (b = -.034, SE = 0.14, p = .017). This association persisted in analyses that further adjusted for health factors, depressive symptoms, and stress. Results suggest that discrimination experiences accelerate biological aging in older African American males and females, alike. This finding helps advance our understanding of how discrimination generates greater disease vulnerability and premature death in African Americans. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genetic findings in anorexia and bulimia nervosa.

PubMed

Hinney, Anke; Scherag, Susann; Hebebrand, Johannes

2010-01-01

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders associated with disordered eating behavior. Heritability estimates derived from twin and family studies are high, so that substantial genetic influences on the etiology can be assumed for both. As the monoaminergic neurotransmitter systems are involved in eating disorders (EDs), candidate gene studies have centered on related genes; additionally, genes relevant for body weight regulation have been considered as candidates. Unfortunately, this approach has yielded very few positive results; confirmed associations or findings substantiated in meta-analyses are scant. None of these associations can be considered unequivocally validated. Systematic genome-wide approaches have been performed to identify genes with no a priori evidence for their relevance in EDs. Family-based scans revealed linkage peaks in single chromosomal regions for AN and BN. Analyses of candidate genes in one of these regions led to the identification of genetic variants associated with AN. Currently, an international consortium is conducting a genome-wide association study for AN, which will hopefully lead to the identification of the first genome-wide significant markers. Copyright © 2010 Elsevier Inc. All rights reserved.

[Associations between socioeconomic status and self-rated health in northeast German rural communities in 1973, 1994, and 2004/2008].

PubMed

Röding, D; Beck, D; Elkeles, T

2013-10-01

This paper reports on selected results from the study "Health and Lifestyle in Rural Northeast Germany". A special characteristic of this study is the regional focus on peripheral rural communities and the trend study design. It was analyzed whether, and to what extent, associations exist between socioeconomic status and self-rated health in this regional context and over time. Thus, regression analyses were conducted using equivalent income, level of school education, and age as independent variables and self-rated health as the dependent variable. Analyses are based on paper-pencil surveys of the adult residents of 14 rural communities chosen at random in northeast Germany, performed in 1973, 1994, and 2004-2008. In all survey waves, a lower level of school education was associated with poor self-rated health. By contrast, associations between income and health were less consistent and constant over time. The associations between income and health are discussed as being specific to East Germany and as a consequence of social transformation in the context of reunification.

Structural social relations and cognitive ageing trajectories: evidence from the Whitehall II cohort study.

PubMed

Elovainio, Marko; Sommerlad, Andrew; Hakulinen, Christian; Pulkki-Råback, Laura; Virtanen, Marianna; Kivimäki, Mika; Singh-Manoux, Archana

2017-11-07

Social relations are important for health, particularly at older ages. We examined the salience of frequency of social contacts and marital status for cognitive ageing trajectories over 21 years, from midlife to early old age. Data are from the Whitehall II cohort study, including 4290 men and 1776 women aged 35-55 years at baseline (1985-88). Frequency of social contacts and marital status were measured in 1985-88 and 1989-90. Assessment of cognitive function on five occasions (1991-94, 1997-99, 2003-04, 2007-09 and 2012-13) included the following tests: short-term memory, inductive reasoning, verbal fluency (phonemic and semantic) and a combined global score. Cognitive trajectories over the study period were analysed using longitudinal latent growth class analyses, and the associations of these latent classes (trajectory memberships) with social relations were analysed using multinominal logistic regression. More frequent social contacts [relative risk (RRR) 0.96, 95% confidence interval (CI) 0.94 - 0.98] and being married (RRR 0.70, 95% CI 0.58 - 0.84) were associated with lower probability of being on a low rather than high cognitive performance trajectory over the subsequent 21 years. These associations persisted after adjustment for covariates. Of the sub-tests, social relations variables had the strongest association with phonemic fluency (RRR 0.95, 95% CI 0.94 - 0.97 for frequent contact; RRR 0.59, 95% CI 0.48 - 0.71 for being married). More frequent social contacts and having a spouse were associated with more favourable cognitive ageing trajectories. Further studies are needed to examine whether interventions designed to improve social connections affect cognitive ageing. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Relationships between menstrual and menopausal attitudes and associated demographic and health characteristics: the Hilo Women's Health Study.

PubMed

Morrison, Lynn A; Sievert, Lynnette L; Brown, Daniel E; Rahberg, Nichole; Reza, Angela

2010-07-01

The objective of this study was to examine the relation of menstrual attitudes to menopausal attitudes and the demographic and health characteristics associated with each. This cross-sectional study consisted of a randomly selected sample of 1,824 respondents aged 16 to 100 years in multi-ethnic Hilo, Hawai'i. Women completed questionnaires for demographic and health information, such as age, ethnicity, education, residency in Hawai'i, menopausal status, exercise, and attitudes toward menstruation and menopause. Women more often chose positive terms, such as "natural," to describe menstruation (60.8%) and menopause (59.4%). In bivariate analyses, post-menopausal women were significantly more likely to have positive menstrual and menopausal attitudes than pre-menopausal women. Factor analyses were used to cluster attitudes followed by linear regression to identify demographic characteristics associated with factor scores. Asian-American ethnicity, higher education, reporting more exercise, and growing up outside of Hawai'i were associated with positive menstrual attitudes. Higher education, older age, post-menopausal status, growing up outside of Hawai'i and having hot flashes were associated with positive menopausal attitudes. Bivariate correlation analyses suggested significant associations between factor scores for menstrual and menopausal attitudes. Both negative and positive menstrual attitudes were positively correlated with the anticipation of menopause, although negative attitudes toward menstruation were negatively correlated with menopause as a positive, natural life event. Demographic variables, specifically education and where one grows up, influenced women's attitudes toward menstruation and menopause and should be considered for inclusion in subsequent multi-ethnic studies. Further research is also warranted in assessing the relationship between menstrual and menopausal attitudes.

Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis.

PubMed

Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E; Treur, Jorien L; Gabrielsen, Maiken E; Munafò, Marcus R; Nordestgaard, Børge Grønne; Åsvold, Bjørn Olav; Romundstad, Pål; Davey Smith, George

2017-12-01

There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. We performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: -0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112 151)

PubMed Central

Davies, G; Marioni, R E; Liewald, D C; Hill, W D; Hagenaars, S P; Harris, S E; Ritchie, S J; Luciano, M; Fawns-Ritchie, C; Lyall, D; Cullen, B; Cox, S R; Hayward, C; Porteous, D J; Evans, J; McIntosh, A M; Gallacher, J; Craddock, N; Pell, J P; Smith, D J; Gale, C R; Deary, I J

2016-01-01

People's differences in cognitive functions are partly heritable and are associated with important life outcomes. Previous genome-wide association (GWA) studies of cognitive functions have found evidence for polygenic effects yet, to date, there are few replicated genetic associations. Here we use data from the UK Biobank sample to investigate the genetic contributions to variation in tests of three cognitive functions and in educational attainment. GWA analyses were performed for verbal–numerical reasoning (N=36 035), memory (N=112 067), reaction time (N=111 483) and for the attainment of a college or a university degree (N=111 114). We report genome-wide significant single-nucleotide polymorphism (SNP)-based associations in 20 genomic regions, and significant gene-based findings in 46 regions. These include findings in the ATXN2, CYP2DG, APBA1 and CADM2 genes. We report replication of these hits in published GWA studies of cognitive function, educational attainment and childhood intelligence. There is also replication, in UK Biobank, of SNP hits reported previously in GWA studies of educational attainment and cognitive function. GCTA-GREML analyses, using common SNPs (minor allele frequency>0.01), indicated significant SNP-based heritabilities of 31% (s.e.m.=1.8%) for verbal–numerical reasoning, 5% (s.e.m.=0.6%) for memory, 11% (s.e.m.=0.6%) for reaction time and 21% (s.e.m.=0.6%) for educational attainment. Polygenic score analyses indicate that up to 5% of the variance in cognitive test scores can be predicted in an independent cohort. The genomic regions identified include several novel loci, some of which have been associated with intracranial volume, neurodegeneration, Alzheimer's disease and schizophrenia. PMID:27046643

Estimating time-varying exposure-outcome associations using case-control data: logistic and case-cohort analyses.

PubMed

Keogh, Ruth H; Mangtani, Punam; Rodrigues, Laura; Nguipdop Djomo, Patrick

2016-01-05

Traditional analyses of standard case-control studies using logistic regression do not allow estimation of time-varying associations between exposures and the outcome. We present two approaches which allow this. The motivation is a study of vaccine efficacy as a function of time since vaccination. Our first approach is to estimate time-varying exposure-outcome associations by fitting a series of logistic regressions within successive time periods, reusing controls across periods. Our second approach treats the case-control sample as a case-cohort study, with the controls forming the subcohort. In the case-cohort analysis, controls contribute information at all times they are at risk. Extensions allow left truncation, frequency matching and, using the case-cohort analysis, time-varying exposures. Simulations are used to investigate the methods. The simulation results show that both methods give correct estimates of time-varying effects of exposures using standard case-control data. Using the logistic approach there are efficiency gains by reusing controls over time and care should be taken over the definition of controls within time periods. However, using the case-cohort analysis there is no ambiguity over the definition of controls. The performance of the two analyses is very similar when controls are used most efficiently under the logistic approach. Using our methods, case-control studies can be used to estimate time-varying exposure-outcome associations where they may not previously have been considered. The case-cohort analysis has several advantages, including that it allows estimation of time-varying associations as a continuous function of time, while the logistic regression approach is restricted to assuming a step function form for the time-varying association.

Relationships between menstrual and menopausal attitudes and associated demographic and health characteristics: The Hilo Women’s Health Study

PubMed Central

Sievert, Lynnette L.; Brown, Daniel E.; Rahberg, Nichole; Reza, Angela

2010-01-01

The objective of this study was to examine the relation of menstrual attitudes to menopausal attitudes and the demographic and health characteristics associated with each. This cross-sectional study consisted of a randomly selected sample of 1824 respondents aged 16 to 100 years in multi-ethnic Hilo, Hawai`i. Women completed questionnaires for demographic and health information, such as age, ethnicity, education, residency in Hawai`i, menopausal status, exercise, and attitudes toward menstruation and menopause. Women more often chose positive terms, such as “natural,” to describe menstruation (60.8%) and menopause (59.4%). In bivariate analyses, post-menopausal women were significantly more likely to have positive menstrual and menopausal attitudes than pre-menopausal women. Factor analyses were used to cluster attitudes followed by linear regression to identify demographic characteristics associated with factor scores. Asian-American ethnicity, higher education, reporting more exercise, and growing up outside of Hawai`i were associated with positive menstrual attitudes. Higher education, older age, post-menopausal status, growing up outside of Hawai`i and having hot flashes were associated with positive menopausal attitudes. Bivariate correlation analyses suggested significant associations between factor scores for menstrual and menopausal attitudes. Both negative and positive menstrual attitudes were positively correlated with the anticipation of menopause, although negative attitudes toward menstruation were negatively correlated with menopause as a positive, natural life event. Demographic variables, specifically education and where one grows up, influenced women’s attitudes toward menstruation and menopause and should be considered for inclusion in subsequent multi-ethnic studies. Further research is also warranted in assessing the relationship between menstrual and menopausal attitudes. PMID:20853216

Methods for meta-analysis of multiple traits using GWAS summary statistics.

PubMed

Ray, Debashree; Boehnke, Michael

2018-03-01

Genome-wide association studies (GWAS) for complex diseases have focused primarily on single-trait analyses for disease status and disease-related quantitative traits. For example, GWAS on risk factors for coronary artery disease analyze genetic associations of plasma lipids such as total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides (TGs) separately. However, traits are often correlated and a joint analysis may yield increased statistical power for association over multiple univariate analyses. Recently several multivariate methods have been proposed that require individual-level data. Here, we develop metaUSAT (where USAT is unified score-based association test), a novel unified association test of a single genetic variant with multiple traits that uses only summary statistics from existing GWAS. Although the existing methods either perform well when most correlated traits are affected by the genetic variant in the same direction or are powerful when only a few of the correlated traits are associated, metaUSAT is designed to be robust to the association structure of correlated traits. metaUSAT does not require individual-level data and can test genetic associations of categorical and/or continuous traits. One can also use metaUSAT to analyze a single trait over multiple studies, appropriately accounting for overlapping samples, if any. metaUSAT provides an approximate asymptotic P-value for association and is computationally efficient for implementation at a genome-wide level. Simulation experiments show that metaUSAT maintains proper type-I error at low error levels. It has similar and sometimes greater power to detect association across a wide array of scenarios compared to existing methods, which are usually powerful for some specific association scenarios only. When applied to plasma lipids summary data from the METSIM and the T2D-GENES studies, metaUSAT detected genome-wide significant loci beyond the ones identified by univariate analyses. Evidence from larger studies suggest that the variants additionally detected by our test are, indeed, associated with lipid levels in humans. In summary, metaUSAT can provide novel insights into the genetic architecture of a common disease or traits. © 2017 WILEY PERIODICALS, INC.

Socioeconomic inequalities in health in older women.

PubMed

Rostad, Berit; Deeg, Dorly J H; Schei, Berit

2009-03-01

Socioeconomic status differentials in health are well documented. Less is known about the socioeconomic variation in health in older people, and in older women in particular. The aim of the study was to examine the association between socioeconomic status and health in older women in relation to two indicators of socioeconomic status and three measures of health, and further, to investigate whether socioeconomic differences in health increase or decrease with advancing age. Data from a cross-sectional population based health survey inviting all women ≥70 years were analysed; 6,380 women aged 70-103 years participated. Logistic regression was applied to analyse variation in health by socioeconomic status. Disadvantaged socioeconomic status (i.e. lower educational levels and previous manual or never been in paid work) was significantly associated with poorer health outcomes, whether measured as self-assessed health or depression. Limiting long-standing illness was significantly associated with never been in paid work. The associations were not attenuated by simultaneous adjustments for health behavioural factors, social support, and marital status. Additional adjustments for medical conditions did only alter the significant association between employment status and limiting long-standing illness. The analyses revealed that educational inequalities did not decrease with advancing age, whereas the results for employment varied across age groups. Our findings suggest an enduring relation between socioeconomic status and health in later life. The study adds to the understanding of the consistent associations between poorer health and social disadvantages at older age. We are not aware of any previous study showing the persistence of social inequalities in health upon adjustments for medical conditions.

The Association Between School Bonding and Smoking Amongst Chilean Adolescents.

PubMed

Gaete, Jorge; Montgomery, Alan; Araya, Ricardo

2015-01-01

The objective of the research was to study the association between school bonding dimensions (school commitment and school attachment) and current adolescent smoking in Chile, controlling for confounding variables using the fifth Chilean School Population National Substance Use Survey, 2003 (CHSS-2003) data set. The CHSS-2003 is a stratified cross-sectional survey that gathers information about personal, familial, peer, and school factors and cigarette use using a self-reported questionnaire. Complete data from 21,956 adolescent students for all the variables of interest were used in the analyses. An exploratory factor analysis (EFA) was performed in order to explore the construct validity of the questionnaire and create the main exposure and potential confounding variables. Multivariable logistic regression analyses were undertaken to study the association between school bonding and smoking. The construct validity of the school attachment and school commitment scales was mainly supported by the EFA. Multivariable analyses showed strong evidence that, after adjusting for factors from different domains, school commitment (student's good grades and school attendance) appears to have a clear inverse association with current smoking (odds ratio [OR]=0.46, 95% confidence interval [CI]: 0.38-0.56). On the other hand, school attachment (their feelings towards their school and their teachers) was not associated with adolescent smoking (OR=1.16, 95% CI: 0.88-1.53). School commitment was strongly associated with current smoking. It is important to further study this variable with the aim of ascertaining whether or not interventions that improve school commitment may prevent or reduce smoking amongst adolescent students.

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.

Distal and proximal factors associated with aggression towards partners and non-partners among patients in substance abuse treatment.

PubMed

Epstein-Ngo, Quyen M; Walton, Maureen A; Sanborn, Michelle; Kraus, Shane; Blow, Fred; Cunningham, Rebecca; Chermack, Stephen T

2014-10-01

Studies of violence in substance use disorder (SUD) treatment settings typically focus on partner aggression (PA) although non-partner aggression (NPA) is also a common problem. This study examines potentially distinct paths of distal and proximal risk factors related to aggression towards non-partners (NPA) and partners (PA) among a SUD treatment sample. The sample included 176 adults reporting past-year violence. Bivariate analyses indicated several distal and proximal factors were associated with NPA and PA. According to multivariate, multiple mediation analyses youth aggression history was a factor for both NPA and PA. Alcohol and cocaine use and psychological distress were associated with NPA; marijuana use was associated with PA. There also was evidence of indirect effects of distal factors on NPA and PA. The results suggest that there may be substantially different dynamics associated with NPA and PA, and have implications for developing screening, assessment and treatment protocols targeting violence among individuals in SUD treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Nested Event-Level Case-Control Study of Drug Use and Sexual Outcomes in Multipartner Encounters Reported by Men Who Have Sex with Men.

PubMed

Melendez-Torres, G J; Hickson, Ford; Reid, David; Weatherburn, Peter; Bonell, Chris

2016-03-01

Previous event-level analyses have often, but not always, found significant associations between drug use and sexual risk behaviour in men who have sex with men (MSM), but these analyses have rarely considered either multipartner encounters specifically, or other sexual outcomes such as pleasure and control. Using data from an internet-based longitudinal survey of MSM, we tested the association between drug use by respondent and by partners and unprotected anal intercourse (UAI), pleasure and control over sexual activity. Overall respondent substance use was significantly associated with increased odds of UAI, though not with pleasure or control. Respondent use of crystal methamphetamine was significantly associated with both increased odds of UAI and decreased odds of control over sexual activity. This analysis agrees with previous studies of dyadic encounters, and specifically suggests that the association between crystal methamphetamine and sexual risk behaviour may be mediated by loss of control.

Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

PubMed Central

Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

2016-01-01

Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

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.

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

PubMed

Hessol, Nancy A; Martínez-Maza, Otoniel; Levine, Alexandra M; Morris, Alison; Margolick, Joseph B; Cohen, Mardge H; Jacobson, Lisa P; Seaberg, Eric C

2015-06-19

To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. Two longitudinal studies of HIV infection in the United States. Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

BAYESIAN LARGE-SCALE MULTIPLE REGRESSION WITH SUMMARY STATISTICS FROM GENOME-WIDE ASSOCIATION STUDIES1

PubMed Central

Zhu, Xiang; Stephens, Matthew

2017-01-01

Bayesian methods for large-scale multiple regression provide attractive approaches to the analysis of genome-wide association studies (GWAS). For example, they can estimate heritability of complex traits, allowing for both polygenic and sparse models; and by incorporating external genomic data into the priors, they can increase power and yield new biological insights. However, these methods require access to individual genotypes and phenotypes, which are often not easily available. Here we provide a framework for performing these analyses without individual-level data. Specifically, we introduce a “Regression with Summary Statistics” (RSS) likelihood, which relates the multiple regression coefficients to univariate regression results that are often easily available. The RSS likelihood requires estimates of correlations among covariates (SNPs), which also can be obtained from public databases. We perform Bayesian multiple regression analysis by combining the RSS likelihood with previously proposed prior distributions, sampling posteriors by Markov chain Monte Carlo. In a wide range of simulations RSS performs similarly to analyses using the individual data, both for estimating heritability and detecting associations. We apply RSS to a GWAS of human height that contains 253,288 individuals typed at 1.06 million SNPs, for which analyses of individual-level data are practically impossible. Estimates of heritability (52%) are consistent with, but more precise, than previous results using subsets of these data. We also identify many previously unreported loci that show evidence for association with height in our analyses. Software is available at https://github.com/stephenslab/rss. PMID:29399241

Association between periodontal disease and dementia: A literature review.

PubMed

Pazos, P; Leira, Y; Domínguez, C; Pías-Peleteiro, J M; Blanco, J; Aldrey, J M

2016-10-22

Periodontal disease and dementia are very prevalent, especially in elderly populations. Multiple studies have shown a link between these diseases; however, the conditions are highly heterogeneous and so is the diagnostic methodology, which may hinder interpretation and comparison of the results. The aim of this article is to provide a critical review of the literature linking these 2 processes. We retrieved 22 studies, most of which were retrospective, and analysed various methodological variables including study population, diagnosis of periodontitis, definition of dementia, adjusted variables, and results. The different aetiopathogenic mechanisms that may affect the progression and interaction of these 2 conditions were also analysed. Although available evidence indicates a positive association between periodontitis and dementia, both the strength of that association and the presence of a causal relationship have yet to be determined. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The relationship between parental depressive symptoms and offspring psychopathology: evidence from a children-of-twins study and an adoption study.

PubMed

McAdams, T A; Rijsdijk, F V; Neiderhiser, J M; Narusyte, J; Shaw, D S; Natsuaki, M N; Spotts, E L; Ganiban, J M; Reiss, David; Leve, L D; Lichtenstein, P; Eley, T C

2015-01-01

Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.

Exposure to traffic-related air pollution and risk of development of childhood asthma: A systematic review and meta-analysis.

PubMed

Khreis, Haneen; Kelly, Charlotte; Tate, James; Parslow, Roger; Lucas, Karen; Nieuwenhuijsen, Mark

2017-03-01

The question of whether children's exposure to traffic-related air pollution (TRAP) contributes to their development of asthma is unresolved. We conducted a systematic review and performed meta-analyses to analyze the association between TRAP and asthma development in childhood. We systematically reviewed epidemiological studies published until 8 September 2016 and available in the Embase, Ovid MEDLINE (R), and Transport databases. We included studies that examined the association between children's exposure to TRAP metrics and their risk of 'asthma' incidence or lifetime prevalence, from birth to age 18years old. We extracted key characteristics of each included study using a predefined data items template and these were tabulated. We used the Critical Appraisal Skills Programme checklists to assess the validity of each included study. Where four or more independent risk estimates were available for a continuous pollutant exposure, we conducted overall and age-specific meta-analyses, and four sensitivity analyses for each summary meta-analytic exposure-outcome association. Forty-one studies met our eligibility criteria. There was notable variability in asthma definitions, TRAP exposure assessment methods and confounder adjustment. The overall random-effects risk estimates (95% CI) were 1.08 (1.03, 1.14) per 0.5×10 -5 m -1 black carbon (BC), 1.05 (1.02, 1.07) per 4μg/m 3 nitrogen dioxide (NO 2 ), 1.48 (0.89, 2.45) per 30μg/m 3 nitrogen oxides (NO x ), 1.03 (1.01, 1.05) per 1μg/m 3 Particulate Matter <2.5μm in diameter (PM 2.5 ), and 1.05 (1.02, 1.08) per 2μg/m 3 Particulate Matter <10μm in diameter (PM 10 ). Sensitivity analyses supported these findings. Across the main analysis and age-specific analysis, the least heterogeneity was seen for the BC estimates, some heterogeneity for the PM 2.5 and PM 10 estimates and the most heterogeneity for the NO 2 and NO x estimates. The overall risk estimates from the meta-analyses showed statistically significant associations for BC, NO 2 , PM 2.5 , PM 10 exposures and risk of asthma development. Our findings support the hypothesis that childhood exposure to TRAP contributes to their development of asthma. Future meta-analyses would benefit from greater standardization of study methods including exposure assessment harmonization, outcome harmonization, confounders' harmonization and the inclusion of all important confounders in individual studies. PROSPERO 2014: CRD42014015448. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combining Genome Wide Association Study and lung eQTL analysis provides evidence for novel genes associated with asthma

PubMed Central

Nieuwenhuis, Maartje A.; Siedlinski, Matteusz; van den Berge, Maarten; Granell, Raquel; Li, Xingnan; Niens, Marijke; van der Vlies, Pieter; Altmüller, Janine; Nürnberg, Peter; Kerkhof, Marjan; van Schayck, Onno C.; Riemersma, Ronald A.; van der Molen, Thys; de Monchy, Jan G.; Bossé, Yohan; Sandford, Andrew; Bruijnzeel-Koomen, Carla A.; van Wijk, Roy G.; ten Hacken, Nick H.; Timens, Wim; Boezen, H. Marike; Henderson, John; Kabesch, Michael; Vonk, Judith M.; Postma, Dirkje S.; Koppelman, Gerard H.

2016-01-01

Background Genome wide association studies (GWAS) of asthma have identified single nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor diagnosed) asthma to our GWAS of asthma with BHR. Methods A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. Results 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genome wide significance after meta-analysis. Five out of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. Conclusions Combining GWAS with subsequent lung eQTL analysis revealed disease associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor’s diagnosed) asthma. PMID:27439200

Genome-Wide Associations Related to Hepatic Histology in Nonalcoholic Fatty Liver Disease in Hispanic Boys.

PubMed

Wattacheril, Julia; Lavine, Joel E; Chalasani, Naga P; Guo, Xiuqing; Kwon, Soonil; Schwimmer, Jeffrey; Molleston, Jean P; Loomba, Rohit; Brunt, Elizabeth M; Chen, Yii-Der Ida; Goodarzi, Mark O; Taylor, Kent D; Yates, Katherine P; Tonascia, James; Rotter, Jerome I

2017-11-01

To identify genetic loci associated with features of histologic severity of nonalcoholic fatty liver disease in a cohort of Hispanic boys. There were 234 eligible Hispanic boys age 2-17 years with clinical, laboratory, and histologic data enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network included in the analysis of 624 297 single nucleotide polymorphisms (SNPs). After the elimination of 4 outliers and 22 boys with cryptic relatedness, association analyses were performed on 208 DNA samples with corresponding liver histology. Logistic regression analyses were carried out for qualitative traits and linear regression analyses were applied for quantitative traits. The median age and body mass index z-score were 12.0 years (IQR, 11.0-14.0) and 2.4 (IQR, 2.1-2.6), respectively. The nonalcoholic fatty liver disease activity score (scores 1-4 vs 5-8) was associated with SNP rs11166927 on chromosome 8 in the TRAPPC9 region (P = 8.7 -07 ). Fibrosis stage was associated with SNP rs6128907 on chromosome 20, near actin related protein 5 homolog (p = 9.9 -07 ). In comparing our results in Hispanic boys with those of previously reported SNPs in adult nonalcoholic steatohepatitis, 2 of 26 susceptibility loci were associated with nonalcoholic fatty liver disease activity score and 2 were associated with fibrosis stage. In this discovery genome-wide association study, we found significant novel gene effects on histologic traits associated with nonalcoholic fatty liver disease activity score and fibrosis that are distinct from those previously recognized by adult nonalcoholic fatty liver disease genome-wide association studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Associations between the peer support relationship, service satisfaction and recovery-oriented outcomes: a correlational study.

PubMed

Thomas, Elizabeth C; Salzer, Mark S

2017-12-18

The working alliance between non-peer providers and mental health consumers is associated with positive outcomes. It is hypothesized that this factor, in addition to other active support elements, is also positively related to peer support service outcomes. This study evaluates correlates of the peer-to-peer relationship and its unique association with service satisfaction and recovery-oriented outcomes. Participants were 46 adults with serious mental illnesses taking part in a peer-brokered self-directed care intervention. Pearson correlation analyses examined associations among peer relationship factors, services-related variables and recovery-oriented outcomes (i.e. empowerment, recovery and quality of life). Hierarchical multiple regression analyses evaluated associations between relationship factors and outcomes over time, controlling for other possible intervention effects. The peer relationship was not related to number of contacts. There were robust associations between the peer relationship and service satisfaction and some recovery-oriented outcomes at 24-months, but not at 12-months. These associations were not explained by other possible intervention effects. This study contributes to a better understanding of the positive, unique association between the peer-to-peer relationship and outcomes, similar to what is found in non-peer-delivered interventions. Implications for program administrators and policymakers seeking to integrate peer specialists into mental health service systems are discussed.

Association between Soy Isoflavone Intake and Breast Cancer Risk for Pre- and Post-Menopausal Women: A Meta-Analysis of Epidemiological Studies

PubMed Central

Zheng, Yi; Wei, Shiqing; Li, Ye; Guo, Tong; Yin, Ping

2014-01-01

Background Conclusions drawn from meta-analyses on the association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women are not fully consistent. These meta-analyses did not explore the influence of different study designs on the pooled results on the basis of distinguishing between pre- and post-menopausal women. Methodology and Principal Findings We performed a meta-analysis of 35 studies which reported results of association between soy isoflavone intake and breast cancer risk for pre- and/or post-menopausal women, calculated pooled odds ratios and their 95% confidence intervals of pre- and post-menopausal women respectively, and further explored soy isoflavone-breast cancer association on the basis of considering different study regions and designs. Summary results suggested that soy isoflavone intake has a protective effect against breast cancer for both pre- and post-menopausal women. However, they are influenced by study design and region. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavone’s protective effect exist in both pre- and post-menopausal women (OR = 0.59, 95%CI: 0.48–0.69 for premenopausal women; OR = 0.59, 95%CI: 0.44–0.74 for postmenopausal women). However, there are some differences between the results pooled from different study designs for women in Asian countries (test for consistency, P = 0.04). Pooled OR of studies on postmenopausal women in Western countries suggested that soy isoflavone intake has a marginally significant protective effect (OR = 0.92; 95%CI: 0.83∼1.00), but further analyses stratifying by study design found no statistically significant association. Conclusions We meta-analyzed more and newer research results, and separated women according to menopausal status to explore soy isoflavone-breast cancer association. We founded that soy isoflavone intake could lower the risk of breast cancer for both pre- and post-menopausal women in Asian countries. However, for women in Western countries, pre- or post-menopausal, there is no evidence to suggest an association between intake of soy isoflavone and breast cancer. PMID:24586662

Genome-wide Association Study for Radiographic Vertebral Fractures: A Potential Role for the 16q24 BMD Locus versus Lessons Learned from Challenging Phenotype Definition.

PubMed

Oei, Ling; Estrada, Karol; Duncan, Emma L; Christiansen, Claus; Liu, Ching-Ti; Langdahl, Bente L; Obermayer-Pietsch, Barbara; Riancho, José A; Prince, Richard L; van Schoor, Natasja M; McCloskey, Eugene; Hsu, Yi-Hsiang; Evangelou, Evangelos; Ntzani, Evangelia; Evans, David M; Alonso, Nerea; Husted, Lise B; Valero, Carmen; Hernandez, Jose L; Lewis, Joshua R; Kaptoge, Stephen K; Zhu, Kun; Cupples, L Adrienne; Medina-Gómez, Carolina; Vandenput, Liesbeth; Kim, Ghi Su; Lee, Seung Hun; Castaño-Betancourt, Martha C; Oei, Edwin H G; Martinez, Josefina; Daroszewska, Anna; van der Klift, Marjolein; Mellström, Dan; Herrera, Lizbeth; Karlsson, Magnus K; Hofman, Albert; Ljunggren, Osten; Pols, Huibert A P; Stolk, Lisette; van Meurs, Joyce B J; Ioannidis, John P A; Zillikens, M Carola; Lips, Paul; Karasik, David; Uitterlinden, André G; Styrkarsdottir, Unnur; Brown, Matthew A; Koh, Jung-Min; Richards, J Brent; Reeve, Jonathan; Ohlsson, Claes; Ralston, Stuart H; Kiel, Douglas P; Rivadeneira, Fernando

2013-10-25

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2,666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at P<5x10 -8 . In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6 x 10 -8 . However, the association was not significant across 5,720 cases and 21,791 controls from 14 studies. Fixed-effects meta analyses summary estimate was 1.06 (95% CI: 0.98-1.14; P=0.17), displaying high degree of heterogeneity (I 2 =57%; Qhet p= 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (P=0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size > 1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions are needed to confirm or reject the involvement of this locus on the risk for vertebral fractures. © 2013.

Body mass index, waist circumference, type 2 diabetes mellitus and risk of liver cancer for U.S. adults

PubMed Central

Campbell, Peter T.; Newton, Christina C.; Freedman, Neal D.; Koshiol, Jill; Alavanja, Michael C.; Beane Freeman, Laura E.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Datta, Mridul; Gaudet, Mia M.; Gaziano, J. Michael; Giovannucci, Edward; Graubard, Barry; Hollenbeck, Albert R.; King, Lindsey; Lee, I-Min; Linet, Martha; Palmer, Julie; Petrick, Jessica L.; Poynter, Jenny N.; Purdue, Mark; Robien, Kim; Rosenberg, Lynn; Sahasrabuddhe, Vikrant; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice; Stevens, Victoria L.; Wactowski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Renehan, Andrew G.; McGlynn, Katherine A.

2016-01-01

Incidence rates for liver cancer have increased threefold since the mid-1970s in the United States in parallel with increasing trends for obesity and type 2 diabetes mellitus (T2DM). We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and T2DM with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and T2DM). Stratified analyses assessed whether the BMI-liver cancer associations differed by hepatitis sera-positivity in nested analyses for a subset of cases (n=220) and controls (n=547). After enrollment, 2,162 incident liver cancer diagnoses were identified. BMI, per 5 kg/m2, was associated with higher risks of liver cancer, more so for men (HR: 1.38; 95% CI: 1.30 to 1.46) than women (HR: 1.25; 95% CI: 1.17 to 1.35; p-interaction: 0.02). WC, per 5 cm, was associated with higher risks of liver cancer, approximately equally by sex (overall, HR: 1.08; 95% CI: 1.04 to 1.13). T2DM was associated with higher risk of liver cancer (HR: 2.61; 95% CI: 2.34 to 2.91). In stratified analyses, there was a null association between BMI and liver cancer risk for participants who were sera-positive for hepatitis. This study suggests that high BMI, high WC, and T2DM are associated with higher risks of liver cancer and that the association may differ by status of viral hepatitis infection. PMID:27742674

Associations between strain in domestic work and self-rated health: a study of employed women in Sweden.

PubMed

Staland-Nyman, Carin; Alexanderson, Kristina; Hensing, Gunnel

2008-01-01

The aim of this study was to analyse the association between strain in domestic work and self-rated health among employed women in Sweden, using two different methods of measuring strain in domestic work. Questionnaire data were collected on health and living conditions in paid and unpaid work for employed women (n=1,417), aged 17-64 years. "Domestic job strain'' was an application of the demand-control model developed by Karasek and Theorell, and "Domestic work equity and marital satisfaction'' was measured by questions on the division of and responsibility for domestic work and relationship with spouse/cohabiter. Self-rated health was measured using the SF-36 Health Survey. Associations were analysed by bivariate and multivariate linear regression analyses, and reported as standardized regression coefficients. Higher strain in domestic work was associated with lower self-rated health, also after controlling for potential confounders and according to both strain measures. "Domestic work equity and marital satisfaction'' showed for example negative associations with mental health beta -0.211 (p<0.001), vitality beta -0.195 (p<0.001), social function -0.132 (p<0.01) and physical role beta -0.115 (p<0.01). The highest associations between "Domestic job strain'' and SF-36 were found for vitality beta -0.156 (p<0.001), mental health beta -0.123 (p<0.001). Strain in domestic work, including perceived inequity in the relationship and lack of a satisfactory relationship with a spouse/cohabiter, was associated with lower self-rated health in this cross-sectional study. Future research needs to address the specific importance of strain in domestic work as a contributory factor to women's ill-health.

Polygenic Risk for Depression Increases Risk of Ischemic Stroke: From the Stroke Genetics Network Study.

PubMed

Wassertheil-Smoller, Sylvia; Qi, Qibin; Dave, Tushar; Mitchell, Braxton D; Jackson, Rebecca D; Liu, Simin; Park, Ki; Salinas, Joel; Dunn, Erin C; Leira, Enrique C; Xu, Huichun; Ryan, Kathleen; Smoller, Jordan W

2018-03-01

Although depression is a risk factor for stroke in large prospective studies, it is unknown whether these conditions have a shared genetic basis. We applied a polygenic risk score (PRS) for major depressive disorder derived from European ancestry analyses by the Psychiatric Genomics Consortium to a genome-wide association study of ischemic stroke in the Stroke Genetics Network of National Institute of Neurological Disorders and Stroke. Included in separate analyses were 12 577 stroke cases and 25 643 controls of European ancestry and 1353 cases and 2383 controls of African ancestry. We examined the association between depression PRS and ischemic stroke overall and with pathogenic subtypes using logistic regression analyses. The depression PRS was associated with higher risk of ischemic stroke overall in both European ( P =0.025) and African ancestry ( P =0.011) samples from the Stroke Genetics Network. Ischemic stroke risk increased by 3.0% (odds ratio, 1.03; 95% confidence interval, 1.00-1.05) for every 1 SD increase in PRS for those of European ancestry and by 8% (odds ratio, 1.08; 95% confidence interval, 1.04-1.13) for those of African ancestry. Among stroke subtypes, elevated risk of small artery occlusion was observed in both European and African ancestry samples. Depression PRS was also associated with higher risk of cardioembolic stroke in European ancestry and large artery atherosclerosis in African ancestry persons. Higher polygenic risk for major depressive disorder is associated with increased risk of ischemic stroke overall and with small artery occlusion. Additional associations with ischemic stroke subtypes differed by ancestry. © 2018 American Heart Association, Inc.

Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis

PubMed Central

Schinasi, Leah; Leon, Maria E.

2014-01-01

This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed. PMID:24762670

Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.

PubMed

Schinasi, Leah; Leon, Maria E

2014-04-23

This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.

Maternal hypertension and risk for hypospadias in offspring.

PubMed

Agopian, A J; Hoang, Thanh T; Mitchell, Laura E; Morrison, Alanna C; Tu, Duong; Nassar, Natasha; Canfield, Mark A

2016-12-01

Hypospadias is one of the most common birth defects in male infants. Maternal hypertension is a suspected risk factor; however, few previous studies have addressed the possibility of reporting bias, and several previous studies have not accounted for hypospadias severity. We analyzed data from the Texas Birth Defects Registry for 10,924 nonsyndromic cases and statewide vital records for deliveries during 1999-2009, using Poisson regression. After adjustment for potential confounders, hypospadias was associated with maternal hypertension (adjusted prevalence ratio: 1.5, 95% confidence interval: 1.4-1.7). Similar associations were observed with gestational and pregestational hypertension, including separate analyses restricted to the subset of cases with severe (second- or third-degree) hypospadias. All of these associations were also similar among the subset of cases with isolated hypospadias (without additional birth defects). To evaluate the potential for bias due to potential hypertension misclassification, we repeated our analyses using logistic regression, comparing the cases to controls with other birth defects. In these analyses, the associations with gestational hypertension were similar, but adjusted associations with pregestational hypertension were no longer observed. Our findings support an association between gestational hypertension and hypospadias in offspring, but also suggest that previously observed associations with pregestational hypertension may have been inflated due to differential misclassification of hypertension (e.g., reporting bias). As gestational hypertension is recognized after hypospadias development, more research is needed to determine if this association reflects an increase in gestational hypertension risk secondary to hypospadias or if both conditions have shared risk factors (e.g., precursors of gestational hypertension). © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

PubMed

Pisani, Paola

2008-02-01

A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoglobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies. Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose.

Bipolar polygenic loading and bipolar spectrum features in major depressive disorder

PubMed Central

Wiste, Anna; Robinson, Elise B; Milaneschi, Yuri; Meier, Sandra; Ripke, Stephan; Clements, Caitlin C; Fitzmaurice, Garrett M; Rietschel, Marcella; Penninx, Brenda W; Smoller, Jordan W; Perlis, Roy H

2014-01-01

Objectives Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of this study was to determine whether this shared genetic liability influences clinical presentation. Methods A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European–American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts. Results A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04). Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ≤ 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8–1.1%. However, analyses in two replication cohorts testing a five feature model did not support this association. Conclusions Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, results are at most inconclusive because of lack of replication. Replication efforts are challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies. PMID:24725193

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112 117)

PubMed Central

Clarke, T-K; Adams, M J; Davies, G; Howard, D M; Hall, L S; Padmanabhan, S; Murray, A D; Smith, B H; Campbell, A; Hayward, C; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Alcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well-known genetic variants in alcohol metabolizing genes, for example, ALDH2 and ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112 117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 14 loci. These include single-nucleotide polymorphisms (SNPs) in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and two loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, CADM2 and FAM69C. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (DRD2, PDE4B). GCTA analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (se=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation (rG) between male and female alcohol consumption was 0.90 (s.e.=0.09, P-value=7.16 × 10−23). Using LD score regression, genetic overlap was found between alcohol consumption and years of schooling (rG=0.18, s.e.=0.03), high-density lipoprotein cholesterol (rG=0.28, s.e.=0.05), smoking (rG=0.40, s.e.=0.06) and various anthropometric traits (for example, overweight, rG=−0.19, s.e.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption. PMID:28937693

TGF-β signalling pathway and breast cancer susceptibility

PubMed Central

Scollen, Serena; Luccarini, Craig; Baynes, Caroline; Driver, Kristy; Humphreys, Manjeet K.; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Pharoah, Paul D.; Easton, Douglas F.; Hesketh, Robin; Metcalfe, James C; Dunning, Alison M

2011-01-01

Background TGF-β acts as a suppressor of primary tumour initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for SNPs tagging seventeen genes in the canonical TGF-β ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signalling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD72. Methods 354 tag SNPs (minor allele frequency>0.05) were selected for genotyping in a staged study design using 6,703 cases and 6,840 controls from the SEARCH study. Significant associations were meta-analysed with data from the NCI Polish Breast Cancer Study (PBCS) (1,966 cases and 2,347 controls) and published data from the Breast Cancer Association Consortium (BCAC). Results Associations of three SNPs, tagging TGFB1 (rs1982073), TGFBR1 (rs10512263) and TGFBR2 (rs4522809) were detected in SEARCH; however associations became weaker in meta-analyses including data from PBCS and BCAC. Tumour sub-type analyses indicated that the TGFB1 rs1982073 association may be confined to increased risk of developing progesterone receptor negative (PR−) tumours (1.18 (95% CI 1.09-1.28), 4.1×10−5 (P value for heterogeneity of ORs by PR status = 2.3 × 10−4)). There was no evidence for breast cancer risk associations with SNPs in the endothelial-specific pathway utilising ALK1/SMADs 1&5 that promotes angiogenesis. Conclusion Common variation in the TGF-β ALK5/SMADs 2&3 signalling pathway, which initiates signalling at the cell surface to inhibit cell proliferation, might be related to risk of specific tumour sub-types. Impact The subtype specific associations require very large studies to be confirmed. PMID:21527583

Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomisation Meta-Analysis in the CARTA Consortium

PubMed Central

Linneberg, Allan; Jacobsen, Rikke K.; Skaaby, Tea; Taylor, Amy E.; Fluharty, Meg E.; Jeppesen, Jørgen L.; Bjorngaard, Johan H.; Åsvold, Bjørn O.; Gabrielsen, Maiken E.; Campbell, Archie; Marioni, Riccardo E.; Kumari, Meena; Marques-Vidal, Pedro; Kaakinen, Marika; Cavadino, Alana; Postmus, Iris; Ahluwalia, Tarunveer S.; Wannamethee, S. Goya; Lahti, Jari; Räikkönen, Katri; Palotie, Aarno; Wong, Andrew; Dalgård, Christine; Ford, Ian; Ben-Shlomo, Yoav; Christiansen, Lene; Kyvik, Kirsten O.; Kuh, Diana; Eriksson, Johan G.; Whincup, Peter H.; Mbarek, Hamdi; de Geus, Eco J.C.; Vink, Jacqueline M.; Boomsma, Dorret I.; Smith, George Davey; Lawlor, Debbie A.; Kisialiou, Aliaksei; McConnachie, Alex; Padmanabhan, Sandosh; Jukema, J. Wouter; Power, Chris; Hyppönen, Elina; Preisig, Martin; Waeber, Gerard; Vollenweider, Peter; Korhonen, Tellervo; Laatikainen, Tiina; Salomaa, Veikko; Kaprio, Jaakko; Kivimaki, Mika; Smith, Blair H.; Hayward, Caroline; Sørensen, Thorkild I.A.; Thuesen, Betina H.; Sattar, Naveed; Morris, Richard W.; Romundstad, Pål R.; Munafò, Marcus R.; Jarvelin, Marjo-Riitta; Husemoen, Lise Lotte N.

2015-01-01

Background Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. Methods and Results Data on 141,317 participants (62,666 never, 40,669 former, 37,982 current smokers) from 23 population-based studies were included in observational and Mendelian randomisation (MR) meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure (SBP, DBP), hypertension, and resting heart rate. For the MR analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower SBP, DBP, and lower hypertension risk, but with higher resting heart rate. In observational analyses amongst current smokers, one cigarette/day higher level of smoking heaviness was associated with higher (0.21 beats/minute; 95% CI 0.19; 0.24) resting heart rate, and slightly higher DBP (0.05 mmHg; 95% CI 0.02; 0.08) and SBP (0.08 mmHg; 95% CI 0.03; 0.13). However, in MR analyses amongst current smokers, while each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 beats/minute/allele; 95% CI 0.18; 0.54), there was no strong association with DBP, SBP, or hypertension. This would suggest a 7 beats/minute higher heart rate in those who smoke 20 cigarettes/day. Conclusions This MR meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate. PMID:26538566

“SNP Snappy”: A Strategy for Fast Genome-Wide Association Studies Fitting a Full Mixed Model

PubMed Central

Meyer, Karin; Tier, Bruce

2012-01-01

A strategy to reduce computational demands of genome-wide association studies fitting a mixed model is presented. Improvements are achieved by utilizing a large proportion of calculations that remain constant across the multiple analyses for individual markers involved, with estimates obtained without inverting large matrices. PMID:22021386

Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

USDA-ARS?s Scientific Manuscript database

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted ...

Associations between yoga practice and joint problems: a cross-sectional survey among 9151 Australian women.

PubMed

Lauche, Romy; Schumann, Dania; Sibbritt, David; Adams, Jon; Cramer, Holger

2017-07-01

Yoga exercises have been associated with joint problems recently, indicating that yoga practice might be potentially dangerous for joint health. This study aimed to analyse whether regular yoga practice is associated with the frequency of joint problems in upper middle-aged Australian women. Women aged 62-67 years from the Australian Longitudinal Study on Women's Health (ALSWH) were questioned in 2013 whether they experienced regular joint pain or problems in the past 12 months and whether they regularly practiced yoga. Associations of joint problems with yoga practice were analysed using Chi-squared tests and multiple logistic regression modelling. Of 9151 women, 29.8% reported regular problems with stiff or painful joints, and 15.2, 11.9, 18.1 and 15.9% reported regular problems with shoulders, hips, knees and feet, respectively, in the past 12 months. Yoga was practiced sometimes by 10.1% and often by 8.4% of women. Practicing yoga was not associated with upper or lower limb joint problems. No association between yoga practice and joint problems has been identified. Further studies are warranted for conclusive judgement of benefits and safety of yoga in relation to joint problems.

Non-replication of the association between 5HTTLPR and response to psychological therapy for child anxiety disorders

PubMed Central

Lester, Kathryn J.; Roberts, Susanna; Keers, Robert; Coleman, Jonathan R. I.; Breen, Gerome; Wong, Chloe C. Y.; Xu, Xiaohui; Arendt, Kristian; Blatter-Meunier, Judith; Bögels, Susan; Cooper, Peter; Creswell, Cathy; Heiervang, Einar R.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; McKinnon, Anna; Morris, Talia; Nauta, Maaike H.; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Smith, Patrick; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Wergeland, Gro Janne; Eley, Thalia C.

2016-01-01

Background We previously reported an association between 5HTTLPR genotype and outcome following cognitive–behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome. Aims To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). Method Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. Results There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes. Conclusions The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples. PMID:26294368

Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study.

PubMed

Crichton, Georgina E; Elias, Merrill F; Alkerwi, Ala'a

2016-05-01

Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aerobrake concepts for NTP systems study

NASA Technical Reports Server (NTRS)

Cruz, Manuel I.

1992-01-01

Design concepts are described for landing large spacecraft masses on the Mars surface in support of manned missions with interplanetary transportation using Nuclear Thermal Propulsion (NTP). Included are the mission and systems analyses, trade studies and sensitivity analyses, design analyses, technology assessment, and derived requirements to support this concept. The mission phases include the Mars de-orbit, entry, terminal descent, and terminal touchdown. The study focuses primarily on Mars surface delivery from orbit after Mars orbit insertion using an NTP. The requirements associated with delivery of logistical supplies, habitats, and other equipment on minimum energy Earth to Mars transfers are also addressed in a preliminary fashion.

Is everything we eat associated with cancer? A systematic cookbook review.

PubMed

Schoenfeld, Jonathan D; Ioannidis, John P A

2013-01-01

Nutritional epidemiology is a highly prolific field. Debates on associations of nutrients with disease risk are common in the literature and attract attention in public media. We aimed to examine the conclusions, statistical significance, and reproducibility in the literature on associations between specific foods and cancer risk. We selected 50 common ingredients from random recipes in a cookbook. PubMed queries identified recent studies that evaluated the relation of each ingredient to cancer risk. Information regarding author conclusions and relevant effect estimates were extracted. When >10 articles were found, we focused on the 10 most recent articles. Forty ingredients (80%) had articles reporting on their cancer risk. Of 264 single-study assessments, 191 (72%) concluded that the tested food was associated with an increased (n = 103) or a decreased (n = 88) risk; 75% of the risk estimates had weak (0.05 > P ≥ 0.001) or no statistical (P > 0.05) significance. Statistically significant results were more likely than nonsignificant findings to be published in the study abstract than in only the full text (P < 0.0001). Meta-analyses (n = 36) presented more conservative results; only 13 (26%) reported an increased (n = 4) or a decreased (n = 9) risk (6 had more than weak statistical support). The median RRs (IQRs) for studies that concluded an increased or a decreased risk were 2.20 (1.60, 3.44) and 0.52 (0.39, 0.66), respectively. The RRs from the meta-analyses were on average null (median: 0.96; IQR: 0.85, 1.10). Associations with cancer risk or benefits have been claimed for most food ingredients. Many single studies highlight implausibly large effects, even though evidence is weak. Effect sizes shrink in meta-analyses.

Brief Motivational Interventions Are Associated With Reductions in Alcohol-Impaired Driving Among College Drinkers

PubMed Central

Teeters, Jenni B.; Borsari, Brian; Martens, Matthew P.; Murphy, James G.

2015-01-01

Objective: Alcohol-impaired (AI) driving among college students remains a significant public health concern and may be the single most risky drinking outcome among young adults. Brief motivational interventions (BMIs) have been shown to reduce alcohol use and problems, but their specific efficacy for decreasing AI driving among college students is unknown. The present study analyzed data from three randomized controlled trials of BMI (Murphy et al., 2010: n = 74; Borsari et al., 2012: n = 530; and Martens et al., 2013: n = 365) to evaluate whether BMIs are associated with reductions in AI driving among college student drinkers. Method: Participants in all three studies were randomized to BMI or control conditions. Participants reported whether they had driven under the influence (yes/no) following the BMI over the follow-up period. Results: Separate binary logistic regression analyses were conducted for each study. For Studies 1 and 2, these analyses revealed that a BMI was significantly associated with reductions in AI driving at the final (6-month and 9-month, respectively) follow-up compared with the control condition. For Study 3, analyses revealed that a single-component BMI focused on the correction of misperceptions of descriptive norms was significantly associated with reductions in AI driving compared with the control group at the final (6-month) follow-up, whereas a single-component BMI focused on the use of protective behavioral strategies was not. Change in drinking level did not mediate the relationship between the condition and the change in AI driving. Conclusions: Counselor-administered BMIs that include descriptive normative feedback are associated with significant reductions in AI driving compared with control. PMID:26402350

Proximity to Liquor Stores and Adolescent Alcohol Intake: A Prospective Study.

PubMed

Trapp, Georgina S A; Knuiman, Matthew; Hooper, Paula; Foster, Sarah

2018-06-01

Cross-sectional studies have reported associations between liquor store availability and alcohol use among adolescents, but few prospective studies have confirmed this association. The aim of this study was to examine whether proximity to liquor stores at age 14 years was associated with alcohol intake at ages 14, 17, and 20 years. Participants of the Western Australian Pregnancy Cohort (Raine) Study (n=999) self-reported alcohol intake at age 14 years (early adolescence, 2003-2005); age 17 years (middle adolescence, 2006-2008); and age 20 years (late adolescence, 2009-2011). A GIS measured proximity to the closest liquor store from participants' home and school addresses at age 14 years. Regression analyses in 2017 assessed the relationship between distance to the closest liquor store around home, school, or both (≤800 m versus >800 m) and alcohol intake. In cross-sectional analyses (age 14 years), having a liquor store within 800 m of school was associated with ever having part of an alcoholic drink (OR=2.34, p=0.003). Also, having a liquor store within 800 m of home or school was associated with ever having part of an alcoholic drink (OR=1.49, p=0.029) and ever having engaged in heavy drinking (OR=1.79, p=0.023). In prospective analyses, liquor store proximity at age 14 years was a significant predictor of alcohol intake at age 17 years (OR=2.34, p=0.032) but not at age 20 years. Liquor store availability in early adolescence may be a risk factor for alcohol intake in early and middle, but not late, adolescence. Improved understanding of the longer-term impacts of liquor store exposure on sensitive populations could help inform future licensing regulations. Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Mobile phone use and risk of tumors: a meta-analysis.

PubMed

Myung, Seung-Kwon; Ju, Woong; McDonnell, Diana D; Lee, Yeon Ji; Kazinets, Gene; Cheng, Chih-Tao; Moskowitz, Joel M

2009-11-20

Case-control studies have reported inconsistent findings regarding the association between mobile phone use and tumor risk. We investigated these associations using a meta-analysis. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916 participants (12,344 patient cases and 25,572 controls), were included in the final analyses. Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98 for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23 studies. However, a significant positive association (harmful effect) was observed in a random-effects meta-analysis of eight studies using blinding, whereas a significant negative association (protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding. Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies reporting this association (odds ratio = 1.18; 95% CI, 1.04 to 1.34). Further, these findings were also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group. The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies providing a higher level of evidence are needed.

Occupational asphalt is not associated with head and neck cancer

PubMed Central

Fogleman, E. V.; Eliot, M.; Michaud, D. S.; Nelson, H. H.; McClean, M. D.

2015-01-01

Background Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). Aims To better elucidate this relationship by including known risk factors in a large case–control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. Methods We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. Results There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever-smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. Conclusions We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen. PMID:26272381

The association between personal income and aging: A population-based 13-year longitudinal study.

PubMed

Lin, Tzu-Yu; Chen, Chia-Yu; Tsao, Chueh-Yung; Hsu, Kuang-Hung

Population aging is set to increase the elder dependency ratio, causing a rapid increase in healthcare expenditures and financial burden on the government. This study aims to construct an aging score from age-related diseases and to perform longitudinal analyses to examine the association between personal income and aging. A total of 86,838 subjects drawn from a community with 384,617 residents in northern Taiwan were examined. Personal income and aging-related diseases were measured from the National Health Insurance database during 1997-2010. Multiple linear regression and stratified analyses were used. Our results indicate that subjects with low personal income (defined as monthly income ≤610 USD) can have high aging scores as calculated by selected aging-related diseases. In stratified analyses, moreover, subjects with low personal income tended to have higher aging scores across different anthropometric groups. The association was particularly evident in subjects >60years old, and they were noted across multiple strata, including those of catastrophic illness as well as type of primary care setting. This study found evidence for association between low income and aging in a population with compulsory health insurance program, where accessibility barriers were low in terms of health care resources and personal socioeconomic status. The economic inequity causes difference in aging process, which deserves for future interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Housing and health in Germany.

PubMed

Pollack, C E; von dem Knesebeck, O; Siegrist, J

2004-03-01

To examine the association between housing tenure and self rated health, controlling for socioeconomic measures and testing the mediating effects of physical features of the home, pollution in the local environment, and relationships with neighbours. Cross sectional panel study with people nested within households. Analyses were performed using multilevel methods. Population based sample in Germany. People aged 16 or older were interviewed in the 1999 wave of the socio-economic panel study (n = 14 055) and nested within households (n = 7381). 44.0% of the population lived in homes that they owned. In bivariate analyses, women, people who live in apartment buildings, reside near cities, live in crowded homes, have homes in need of renovation, report higher pollution, and have distant contact with neighbours are more likely to live in rented homes. In multilevel analyses, renting a home was found to be associated with poor self rated health (OR 1.48, 95% CI 1.31 to 1.68). This relation persisted after controlling for education and income and was partially mediated by the need for household renovation, the perception of air and noise pollution in the local area, and distant relationship with neighbours, all of which were significantly associated with self rated health. This study provides evidence that home ownership is significantly associated with self rated health in Germany, and this relation may be, in part, mediated by physical and social features of home and neighbourhood.

Factors Affecting Sugar-Sweetened Beverage Availability in Competitive Venues of US Secondary Schools

ERIC Educational Resources Information Center

Terry-McElrath, Yvonne M.; O'Malley, Patrick M.; Johnston, Lloyd D.

2012-01-01

Background: This study explores sugar-sweetened beverage (SSB) availability in US secondary school competitive venues during the first 3 years following the school wellness policy requirement (2007-2009). Furthermore, analyses examine associations with school policy and SSB availability. Methods: Analyses use questionnaire data from 757 middle and…

43 CFR 10010.36 - Environmental review and consultation requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... comply with the requirements of other federal or state laws and regulations, the associated analyses, studies, or surveys will be identified as such and discussed in the text of the EIS and the cover sheet will so indicate. Any supporting analyses or reports to the NEPA documents will be incorporated by...

Associations Between Traumatic Brain Injury History and Future Headache Severity in Veterans: A Longitudinal Study.

PubMed

Suri, Pradeep; Stolzmann, Kelly; Iverson, Katherine M; Williams, Rhonda; Meterko, Mark; Yan, Kun; Gormley, Katelyn; Pogoda, Terri K

2017-11-01

To determine whether traumatic brain injury (TBI) history is associated with worse headache severity outcomes. Prospective cohort study. Department of Veterans Affairs (VA) outpatient clinics. Veterans (N=2566) who completed a mail follow-up survey an average of 3 years after a comprehensive TBI evaluation (CTBIE). Not applicable. The presence or absence of TBI, and TBI severity were evaluated by a trained clinician and classified according to VA/Department of Defense clinical practice guidelines. Headache severity was evaluated at both the baseline CTBIE assessment and 3-year follow-up using a 5-level headache score ranging from 0 ("none") to 4 ("very severe") based on headache-associated activity interference in the past 30 days. We examined associations of mild and moderate/severe TBI history, as compared to no TBI history, with headache severity in cross-sectional and longitudinal analyses, with and without adjustment for potential confounders. Mean headache severity scores were 2.4 at baseline and 2.3 at 3-year follow-up. Mild TBI was associated with greater headache severity in multivariate-adjusted cross-sectional analyses (β [SE]=.61 [.07], P<.001), as compared with no TBI, but not in longitudinal analyses (β [SE]=.09 [.07], P=.20). Moderate/severe TBI was significantly associated with greater headache severity in both cross-sectional (β [SE]=.66 [.09], P<.001) and longitudinal analyses (β [SE]=.18 [.09], P=.04). Headache outcomes are poor in veterans who receive VA TBI evaluations, irrespective of past TBI exposure, but significantly worse in those with a history of moderate/severe TBI. No association was found between mild TBI and future headache severity in veterans. Veterans with headache presenting for TBI evaluations, and particularly those with moderate/severe TBI, may benefit from further evaluation and treatment of headache. Published by Elsevier Inc.

Milk Intakes Are Not Associated with Percent Body Fat in Children from Ages 10 to 13 Years12

PubMed Central

Noel, Sabrina E.; Ness, Andrew R.; Northstone, Kate; Emmett, Pauline; Newby, P. K.

2011-01-01

Epidemiologic studies report conflicting results for the relationship between milk intake and adiposity in children. We examined prospective and cross-sectional associations between milk intake and percent body fat among 2245 children from the Avon Longitudinal Study of Parents and Children. Cross-sectional analyses were performed at age 13 y between total, full-fat, and reduced-fat milk intake assessed using 3-d dietary records and body fat from DXA. Prospective analyses were conducted between milk intakes at age 10 y and body fat at 11 and 13 y. Models were adjusted for age, sex, height, physical activity, pubertal status, maternal BMI, maternal education, and intakes of total fat, sugar-sweetened beverages, 100% fruit juice, and ready-to-eat cereals; baseline BMI was added to prospective models. Subset analyses were performed for those with plausible dietary intakes. Mean milk consumption at 10 and 13 y was (mean ± SD) 0.90 ± 0.73 and 0.85 ± 0.78 servings/d [1 serving = 8 oz of milk (244 g of plain and 250 g flavored milk)], respectively. Cross-sectional results indicated an inverse association between full-fat milk intake and body fat [β = −0.47 (95% CI = −0.76, −0.19); P = 0.001]. Milk intake at age 10 y was inversely associated with body fat at 11 y [β = −0.16 g/d (95%CI = −0.28, −0.04); P = 0.01], but not among those with plausible dietary intakes, suggesting that this association was influenced by dietary measurement errors. Milk intake was not associated with body fat at age 13 y after adjustment. Although our prospective results corroborate other findings of a null associations between milk intake and adiposity, our inconsistent findings across analyses suggest further investigation is needed to clarify the relation, and accounting for dietary reporting errors is an important consideration. PMID:21940511

'Whose atlas I use, his song I sing?' - The impact of anatomical atlases on fiber tract contributions to cognitive deficits after stroke.

PubMed

de Haan, Bianca; Karnath, Hans-Otto

2017-12-01

Nowadays, different anatomical atlases exist for the anatomical interpretation of the results from neuroimaging and lesion analysis studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. A major problem with the use of different atlases in different studies, however, is that the anatomical interpretation of neuroimaging and lesion analysis results might vary as a function of the atlas used. This issue might be particularly prominent in studies that investigate the contribution of white matter fiber tract integrity to cognitive (dys)function. We used a single large-sample dataset of right brain damaged stroke patients with and without cognitive deficit (here: spatial neglect) to systematically compare the influence of three different, widely-used white matter fiber tract atlases (1 histology-based atlas and 2 DTI tractography-based atlases) on conclusions concerning the involvement of white matter fiber tracts in the pathogenesis of cognitive dysfunction. We both calculated the overlap between the statistical lesion analysis results and each long association fiber tract (topological analyses) and performed logistic regressions on the extent of fiber tract damage in each individual for each long association white matter fiber tract (hodological analyses). For the topological analyses, our results suggest that studies that use tractography-based atlases are more likely to conclude that white matter integrity is critical for a cognitive (dys)function than studies that use a histology-based atlas. The DTI tractography-based atlases classified approximately 10 times as many voxels of the statistical map as being located in a long association white matter fiber tract than the histology-based atlas. For hodological analyses on the other hand, we observed that the conclusions concerning the overall importance of long association fiber tract integrity to cognitive function do not necessarily depend on the white matter atlas used, but conclusions may vary as a function of atlas used at the level of individual fiber tracts. Moreover, these analyses revealed that hodological studies that express the individual extent of injury to each fiber tract as a binomial variable are more likely to conclude that white matter integrity is critical for a cognitive function than studies that express the individual extent of injury to each fiber tract as a continuous variable. Copyright © 2017 Elsevier Inc. All rights reserved.

Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes.

PubMed

Poole, Robin; Kennedy, Oliver J; Roderick, Paul; Fallowfield, Jonathan A; Hayes, Peter C; Parkes, Julie

2017-11-22

Objectives  To evaluate the existing evidence for associations between coffee consumption and multiple health outcomes. Design  Umbrella review of the evidence across meta-analyses of observational and interventional studies of coffee consumption and any health outcome. Data sources  PubMed, Embase, CINAHL, Cochrane Database of Systematic Reviews, and screening of references. Eligibility criteria for selecting studies  Meta-analyses of both observational and interventional studies that examined the associations between coffee consumption and any health outcome in any adult population in all countries and all settings. Studies of genetic polymorphisms for coffee metabolism were excluded. Results  The umbrella review identified 201 meta-analyses of observational research with 67 unique health outcomes and 17 meta-analyses of interventional research with nine unique outcomes. Coffee consumption was more often associated with benefit than harm for a range of health outcomes across exposures including high versus low, any versus none, and one extra cup a day. There was evidence of a non-linear association between consumption and some outcomes, with summary estimates indicating largest relative risk reduction at intakes of three to four cups a day versus none, including all cause mortality (relative risk 0.83 (95% confidence interval 0.79 to 0.88), cardiovascular mortality (0.81, 0.72 to 0.90), and cardiovascular disease (0.85, 0.80 to 0.90). High versus low consumption was associated with an 18% lower risk of incident cancer (0.82, 0.74 to 0.89). Consumption was also associated with a lower risk of several specific cancers and neurological, metabolic, and liver conditions. Harmful associations were largely nullified by adequate adjustment for smoking, except in pregnancy, where high versus low/no consumption was associated with low birth weight (odds ratio 1.31, 95% confidence interval 1.03 to 1.67), preterm birth in the first (1.22, 1.00 to 1.49) and second (1.12, 1.02 to 1.22) trimester, and pregnancy loss (1.46, 1.06 to 1.99). There was also an association between coffee drinking and risk of fracture in women but not in men. Conclusion  Coffee consumption seems generally safe within usual levels of intake, with summary estimates indicating largest risk reduction for various health outcomes at three to four cups a day, and more likely to benefit health than harm. Robust randomised controlled trials are needed to understand whether the observed associations are causal. Importantly, outside of pregnancy, existing evidence suggests that coffee could be tested as an intervention without significant risk of causing harm. Women at increased risk of fracture should possibly be excluded. 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.

Job Strain and Tobacco Smoking: An Individual-Participant Data Meta-Analysis of 166 130 Adults in 15 European Studies

PubMed Central

Heikkilä, Katriina; Nyberg, Solja T.; Fransson, Eleonor I.; Alfredsson, Lars; De Bacquer, Dirk; Bjorner, Jakob B.; Bonenfant, Sébastien; Borritz, Marianne; Burr, Hermann; Clays, Els; Casini, Annalisa; Dragano, Nico; Erbel, Raimund; Geuskens, Goedele A.; Goldberg, Marcel; Hooftman, Wendela E.; Houtman, Irene L.; Joensuu, Matti; Jöckel, Karl-Heinz; Kittel, France; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Kouvonen, Anne; Leineweber, Constanze; Lunau, Thorsten; Madsen, Ida E. H.; Hanson, Linda L. Magnusson; Marmot, Michael G.; Nielsen, Martin L.; Nordin, Maria; Pentti, Jaana; Salo, Paula; Rugulies, Reiner; Steptoe, Andrew; Siegrist, Johannes; Suominen, Sakari; Vahtera, Jussi; Virtanen, Marianna; Väänänen, Ari; Westerholm, Peter; Westerlund, Hugo; Zins, Marie; Theorell, Töres; Hamer, Mark; Ferrie, Jane E.; Singh-Manoux, Archana; Batty, G. David; Kivimäki, Mika

2012-01-01

Background Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults. Methodology and Principal Findings We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking. Conclusions Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers. PMID:22792154

The Genetic Architecture of Complex Traits in Teosinte (Zea mays ssp. parviglumis): New Evidence from Association Mapping

USDA-ARS?s Scientific Manuscript database

Our previous association analyses showed that variation at major regulatory genes contributes to standing variation for complex traits in Balsas teosinte, the progenitor of maize. This study expands our previous association mapping effort in teosinte by testing 123 markers in 52 candidate genes for ...

How Genes Modulate Patterns of Aging-Related Changes on the Way to 100: Biodemographic Models and Methods in Genetic Analyses of Longitudinal Data

PubMed Central

Yashin, Anatoliy I.; Arbeev, Konstantin G.; Wu, Deqing; Arbeeva, Liubov; Kulminski, Alexander; Kulminskaya, Irina; Akushevich, Igor; Ukraintseva, Svetlana V.

2016-01-01

Background and Objective To clarify mechanisms of genetic regulation of human aging and longevity traits, a number of genome-wide association studies (GWAS) of these traits have been performed. However, the results of these analyses did not meet expectations of the researchers. Most detected genetic associations have not reached a genome-wide level of statistical significance, and suffered from the lack of replication in the studies of independent populations. The reasons for slow progress in this research area include low efficiency of statistical methods used in data analyses, genetic heterogeneity of aging and longevity related traits, possibility of pleiotropic (e.g., age dependent) effects of genetic variants on such traits, underestimation of the effects of (i) mortality selection in genetically heterogeneous cohorts, (ii) external factors and differences in genetic backgrounds of individuals in the populations under study, the weakness of conceptual biological framework that does not fully account for above mentioned factors. One more limitation of conducted studies is that they did not fully realize the potential of longitudinal data that allow for evaluating how genetic influences on life span are mediated by physiological variables and other biomarkers during the life course. The objective of this paper is to address these issues. Data and Methods We performed GWAS of human life span using different subsets of data from the original Framingham Heart Study cohort corresponding to different quality control (QC) procedures and used one subset of selected genetic variants for further analyses. We used simulation study to show that approach to combining data improves the quality of GWAS. We used FHS longitudinal data to compare average age trajectories of physiological variables in carriers and non-carriers of selected genetic variants. We used stochastic process model of human mortality and aging to investigate genetic influence on hidden biomarkers of aging and on dynamic interaction between aging and longevity. We investigated properties of genes related to selected variants and their roles in signaling and metabolic pathways. Results We showed that the use of different QC procedures results in different sets of genetic variants associated with life span. We selected 24 genetic variants negatively associated with life span. We showed that the joint analyses of genetic data at the time of bio-specimen collection and follow up data substantially improved significance of associations of selected 24 SNPs with life span. We also showed that aging related changes in physiological variables and in hidden biomarkers of aging differ for the groups of carriers and non-carriers of selected variants. Conclusions . The results of these analyses demonstrated benefits of using biodemographic models and methods in genetic association studies of these traits. Our findings showed that the absence of a large number of genetic variants with deleterious effects may make substantial contribution to exceptional longevity. These effects are dynamically mediated by a number of physiological variables and hidden biomarkers of aging. The results of these research demonstrated benefits of using integrative statistical models of mortality risks in genetic studies of human aging and longevity. PMID:27773987

Medical costs and quality-adjusted life years associated with smoking: a systematic review.

PubMed

Feirman, Shari P; Glasser, Allison M; Teplitskaya, Lyubov; Holtgrave, David R; Abrams, David B; Niaura, Raymond S; Villanti, Andrea C

2016-07-27

Estimated medical costs ("T") and QALYs ("Q") associated with smoking are frequently used in cost-utility analyses of tobacco control interventions. The goal of this study was to understand how researchers have addressed the methodological challenges involved in estimating these parameters. Data were collected as part of a systematic review of tobacco modeling studies. We searched five electronic databases on July 1, 2013 with no date restrictions and synthesized studies qualitatively. Studies were eligible for the current analysis if they were U.S.-based, provided an estimate for Q, and used a societal perspective and lifetime analytic horizon to estimate T. We identified common methods and frequently cited sources used to obtain these estimates. Across all 18 studies included in this review, 50 % cited a 1992 source to estimate the medical costs associated with smoking and 56 % cited a 1996 study to derive the estimate for QALYs saved by quitting or preventing smoking. Approaches for estimating T varied dramatically among the studies included in this review. T was valued as a positive number, negative number and $0; five studies did not include estimates for T in their analyses. The most commonly cited source for Q based its estimate on the Health Utilities Index (HUI). Several papers also cited sources that based their estimates for Q on the Quality of Well-Being Scale and the EuroQol five dimensions questionnaire (EQ-5D). Current estimates of the lifetime medical care costs and the QALYs associated with smoking are dated and do not reflect the latest evidence on the health effects of smoking, nor the current costs and benefits of smoking cessation and prevention. Given these limitations, we recommend that researchers conducting economic evaluations of tobacco control interventions perform extensive sensitivity analyses around these parameter estimates.

Evaluation of a SNP map of 6q24-27 confirms diabetic nephropathy loci and identifies novel associations type 2 diabetes patients enriched with nephropathy from an African American population

PubMed Central

Leak, Tennille S.; Mychaleckyj, Josyf C.; Smith, Shelly G.; Keene, Keith L.; Gordon, Candace J.; Hicks, Pamela J.; Freedman, Barry I.; Bowden, Donald W.; Sale, Michèle M.

2009-01-01

Previously we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from 247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24-27 (LOD 2.26). To comprehensively evaluate this region we performed a 2-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on the basis of linkage disequilibrium (LD) in 300 AAT2DM-ESRD subjects, 311 AA controls, 43 European American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association (P<0.05) in one or more of tests of association: allelic (n=33), dominant (n=36), additive (n=29), or recessive (n=34) genotypic models, and 2- (n=47) and 3-SNP (n=43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with a predicted 2-SNP “risk” haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes; including suggestive associations in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within 6q24-27 in AA. PMID:18560894

Associations of specific phobia and its subtypes with physical diseases: an adult community study.

PubMed

Witthauer, Cornelia; Ajdacic-Gross, Vladeta; Meyer, Andrea Hans; Vollenweider, Peter; Waeber, Gerard; Preisig, Martin; Lieb, Roselind

2016-05-21

Specific phobia is the most prevalent anxiety disorder in the community and is associated with substantial impairment. Comorbidity with physical diseases is assumed and has important implications for etiology, treatment, or prevention of the comorbid conditions. However, due to methodological issues data are limited and subtypes of specific phobia have not been investigated yet. We examined the association of specific phobia and its subtypes with physical diseases in a representative community sample with physician-diagnosed physical diseases and diagnostic criteria of specific phobia. Data of the German Mental Health Survey from 4181 subjects aged 18-65 years were used. Specific phobia was diagnosed using M-CIDI/DIA-X interview; physical diseases were assessed through a self-report questionnaire and a medical interview. Logistic regression analyses adjusted for sex were calculated. Specific phobia was associated with cardiac diseases, gastrointestinal diseases, respiratory diseases, arthritic conditions, migraine, and thyroid diseases (odds ratios between 1.49 and 2.53). Among the subtypes, different patterns of associations with physical diseases were established. The findings were partially replicated in the Swiss PsyCoLaus Study. Our analyses show that subjects with specific phobia have an increased probability for specific physical diseases. From these analyses etiological mechanisms of specific phobia and physical disease can be deduced. As subtypes differed in their patterns of associations with physical diseases, different etiological mechanisms may play a role. The findings are highly relevant for public health in terms of prevention and therapy of the comorbid conditions.

Evaluation of European Schizophrenia GWAS Loci in Asian Populations via Comprehensive Meta-Analyses.

PubMed

Xiao, Xiao; Luo, Xiong-Jian; Chang, Hong; Liu, Zichao; Li, Ming

2017-08-01

Schizophrenia is a severe and highly heritable neuropsychiatric disorder. Recent genetic analyses including genome-wide association studies (GWAS) have implicated multiple genome-wide significant variants for schizophrenia among European populations. However, many of these risk variants were not largely validated in other populations of different ancestry such as Asians. To validate whether these European GWAS significant loci are associated with schizophrenia in Asian populations, we conducted a systematic literature search and meta-analyses on 19 single nucleotide polymorphisms (SNPs) in Asian populations by combining all available case-control and family-based samples, including up to 30,000 individuals. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (ORs) and 95 % confidence intervals (CIs). Among the 19 GWAS loci, we replicated the risk associations of nine markers (e.g., SNPs at VRK2, ITIH3/4, NDST3, NOTCH4) surpassing significance level (two-tailed P < 0.05), and three additional SNPs in MIR137 and ZNF804A also showed trend associations (one-tailed P < 0.05). These risk associations are in the same directions of allelic effects between Asian replication samples and initial European GWAS findings, and the successful replications of these GWAS loci in a different ethnic group provide stronger evidence for their clinical associations with schizophrenia. Further studies, focusing on the molecular mechanisms of these GWAS significant loci, will become increasingly important for understanding of the pathogenesis to schizophrenia.

Reporting and methodological quality of meta-analyses in urological literature.

PubMed

Xia, Leilei; Xu, Jing; Guzzo, Thomas J

2017-01-01

To assess the overall quality of published urological meta-analyses and identify predictive factors for high quality. We systematically searched PubMed to identify meta-analyses published from January 1st, 2011 to December 31st, 2015 in 10 predetermined major paper-based urology journals. The characteristics of the included meta-analyses were collected, and their reporting and methodological qualities were assessed by the PRISMA checklist (27 items) and AMSTAR tool (11 items), respectively. Descriptive statistics were used for individual items as a measure of overall compliance, and PRISMA and AMSTAR scores were calculated as the sum of adequately reported domains. Logistic regression was used to identify predictive factors for high qualities. A total of 183 meta-analyses were included. The mean PRISMA and AMSTAR scores were 22.74 ± 2.04 and 7.57 ± 1.41, respectively. PRISMA item 5, protocol and registration, items 15 and 22, risk of bias across studies, items 16 and 23, additional analysis had less than 50% adherence. AMSTAR item 1, " a priori " design, item 5, list of studies and item 10, publication bias had less than 50% adherence. Logistic regression analyses showed that funding support and " a priori " design were associated with superior reporting quality, following PRISMA guideline and " a priori " design were associated with superior methodological quality. Reporting and methodological qualities of recently published meta-analyses in major paper-based urology journals are generally good. Further improvement could potentially be achieved by strictly adhering to PRISMA guideline and having " a priori " protocol.

Hydronephrosis in patients with cervical cancer: an assessment of morbidity and survival.

PubMed

Patel, Krishna; Foster, Nathan R; Kumar, Amanika; Grudem, Megan; Longenbach, Sherri; Bakkum-Gamez, Jamie; Haddock, Michael; Dowdy, Sean; Jatoi, Aminah

2015-05-01

Hydronephrosis is a frequently observed but understudied complication in patients with cervical cancer. To better characterize hydronephrosis in cervical cancer patients, the current study sought (1) to describe hydronephrosis-associated morbidity and (2) to analyze the prognostic effect of hydronephrosis in patients with a broad range of cancer stages over time. The Mayo Clinic Tumor Registry was interrogated for all invasive cervical cancer patients seen at the Mayo Clinic from 2008 through 2013 in Rochester, Minnesota; these patients' medical records were then reviewed in detail. Two hundred seventy-nine cervical cancer patients with a median age of 49 years and a range of cancer stages were included. Sixty-five patients (23 %) were diagnosed with hydronephrosis at some point during their disease course. In univariate analyses, hydronephrosis was associated with advanced cancer stage (p < 0.0001), squamous histology (p = 0.0079), and nonsurgical cancer treatment (p = 0.0039). In multivariate analyses, stage and tumor histology were associated with hydronephrosis. All but one patient underwent stent placement or urinary diversion; hydronephrosis-related morbidity included pain, urinary tract infections, nausea and vomiting, renal failure, and urinary tract bleeding. In landmark univariate survival analyses, hydronephrosis was associated with worse survival at all time points. In landmark multivariate analyses (adjusted for patient age, stage, cancer treatment, and tumor histology), hydronephrosis was associated with a trend toward worse survival over time (hazard ratios ranged from 1.47 to 4.69). Hydronephrosis in cervical cancer patients is associated with notable morbidity. It is also associated with trends toward worse survival-even if it occurs after the original cancer diagnosis.

Association between birthweight and later body mass index: an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project

PubMed Central

Jelenkovic, Aline; Yokoyama, Yoshie; Sund, Reijo; Pietiläinen, Kirsi H; Hur, Yoon-Mi; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Toos CEM; Ooki, Syuichi; Saudino, Kimberly J; Stazi, Maria A; Fagnani, Corrado; D’Ippolito, Cristina; Nelson, Tracy L; Whitfield, Keith E; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Heikkilä, Kauko; Cutler, Tessa L; Hopper, John L; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth JF; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Burt, S Alexandra; Klump, Kelly L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas Sevenius; Craig, Jeffrey M; Saffery, Richard; Rasmussen, Finn; Tynelius, Per; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Haworth, Claire MA; Plomin, Robert; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Boomsma, Dorret I; Sørensen, Thorkild IA; Kaprio, Jaakko; Silventoinen, Karri

2017-01-01

Abstract Background There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. Methods This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. Results At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. Conclusions These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood. PMID:28369451

Associations between Grawe's general mechanisms of change and Young's early maladaptive schemas in psychotherapy research: a comparative study of change processes.

PubMed

Mander, Johannes V; Jacob, Gitta A; Götz, Lea; Sammet, Isa; Zipfel, Stephan; Teufel, Martin

2015-01-01

The study aimed at analyzing associations between Grawe's general mechanisms of change and Young's early maladaptive schemas (EMS). Therefore, 98 patients completed the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP), the Young Shema Questionnaire-Short Form Revised (YSQ S3R), and diverse outcome measures at the beginning and end of treatment. Our results are important for clinical applications, as we demonstrated strong predictive effects of change mechanisms on schema domains using regression analyses and cross-lagged panel models. Resource activation experiences seem to be especially crucial in fostering alterations in EMS, as this change mechanism demonstrated significant associations with several schema domains. Future research should investigate these aspects in more detail using observer-based micro-process analyses.

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

PubMed

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

2014-01-01

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

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.

Association between Neighborhood Walkability, Cardiorespiratory Fitness and Body-Mass Index

PubMed Central

Hoehner, Christine M.; Handy, Susan L.; Yan, Yan; Blair, teven N.; Berrigan, David

2011-01-01

Many studies have found cross-sectional associations between characteristics of the neighborhood built environment and physical activity (PA) behavior. However, most are based on self-reported PA, which is known to result in overestimation of PA and differential misclassification by demographic and biological characteristics. Cardiorespiratory fitness (CRF) is an objective marker of PA because it is primarily determined by PA. Furthermore, it is causally related to long-term health outcomes. Therefore, analyses of the association between CRF and built environment could strengthen arguments for the importance of built environment influences on health. We examined the association between neighborhood walkability and CRF and body-mass index (BMI). This cross-sectional analysis included 16,543 adults (5,017 women, 11,526 men) aged 18–90 years with home addresses in Texas who had a comprehensive clinical examination between 1987 and 2005. Outcomes included CRF from total duration on a maximal exercise treadmill test and measured BMI. Three neighborhood walkability factors emerged from principal components analyses of block-group measures derived from the U.S. Census. In multilevel adjusted analyses, the neighborhood walkability factors were significantly associated with CRF and BMI among men and women in the expected direction. An interaction between one of the neighborhood factors and age was also observed. The interaction suggested that living in neighborhoods with older homes and with residents traveling shorter distances to work was more strongly positively associated with CRF among younger adults and more strongly negatively associated with BMI among older adults. In conclusion, neighborhood characteristics hypothesized to support more PA and less driving were associated with higher levels of CRF and lower BMI. Demonstration of an association between built environment characteristics and CRF is a significant advance over past studies based on self-reported PA. Nevertheless, stronger causal evidence depends on more robust study designs and sophisticated measures of the environment, behavior, and their physiological consequences. PMID:22030212

Population-genetic comparison of the Sorbian isolate population in Germany with the German KORA population using genome-wide SNP arrays

PubMed Central

2011-01-01

Background The Sorbs are an ethnic minority in Germany with putative genetic isolation, making the population interesting for disease mapping. A sample of N = 977 Sorbs is currently analysed in several genome-wide meta-analyses. Since genetic differences between populations are a major confounding factor in genetic meta-analyses, we compare the Sorbs with the German outbred population of the KORA F3 study (N = 1644) and other publically available European HapMap populations by population genetic means. We also aim to separate effects of over-sampling of families in the Sorbs sample from effects of genetic isolation and compare the power of genetic association studies between the samples. Results The degree of relatedness was significantly higher in the Sorbs. Principal components analysis revealed a west to east clustering of KORA individuals born in Germany, KORA individuals born in Poland or Czech Republic, Half-Sorbs (less than four Sorbian grandparents) and Full-Sorbs. The Sorbs cluster is nearest to the cluster of KORA individuals born in Poland. The number of rare SNPs is significantly higher in the Sorbs sample. FST between KORA and Sorbs is an order of magnitude higher than between different regions in Germany. Compared to the other populations, Sorbs show a higher proportion of individuals with runs of homozygosity between 2.5 Mb and 5 Mb. Linkage disequilibrium (LD) at longer range is also slightly increased but this has no effect on the power of association studies. Oversampling of families in the Sorbs sample causes detectable bias regarding higher FST values and higher LD but the effect is an order of magnitude smaller than the observed differences between KORA and Sorbs. Relatedness in the Sorbs also influenced the power of uncorrected association analyses. Conclusions Sorbs show signs of genetic isolation which cannot be explained by over-sampling of relatives, but the effects are moderate in size. The Slavonic origin of the Sorbs is still genetically detectable. Regarding LD structure, a clear advantage for genome-wide association studies cannot be deduced. The significant amount of cryptic relatedness in the Sorbs sample results in inflated variances of Beta-estimators which should be considered in genetic association analyses. PMID:21798003

Anorexia nervosa and bulimia nervosa: A meta-analysis of executive functioning.

PubMed

Hirst, Rayna B; Beard, Charlotte L; Colby, Katrina A; Quittner, Zoe; Mills, Brent M; Lavender, Jason M

2017-12-01

Research investigating the link between eating disorder (ED) diagnosis and executive dysfunction has had conflicting results, yet no meta-analyses have examined the overall association of ED pathology with executive functioning (EF). Effect sizes were extracted from 32 studies comparing ED groups (27 of anorexia nervosa, 9 of bulimia nervosa) with controls to determine the grand mean effect on EF. Analyses included effects for individual EF measures, as well as an age-based subgroup analysis. There was a medium effect of ED diagnosis on executive functioning, with bulimia nervosa demonstrating a larger effect (Hedges's g=-0.70) than anorexia nervosa (g=-0.41). Within anorexia nervosa studies, subgroup analyses were conducted for age and diagnostic subtype. The effect of anorexia nervosa on EF was largest in adults; however, subgroup differences for age were not significant. Anorexia and bulimia nervosa are associated with EF deficits, which are particularly notable for individuals with bulimia nervosa. The present analysis includes recommendations for future studies regarding study design and EF measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses.

PubMed

Vermeulen, Roel; Saberi Hosnijeh, Fatemeh; Bodinier, Barbara; Portengen, Lützen; Liquet, Benoît; Garrido-Manriquez, Javiera; Lokhorst, Henk; Bergdahl, Ingvar A; Kyrtopoulos, Soterios A; Johansson, Ann-Sofie; Georgiadis, Panagiotis; Melin, Beatrice; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Vineis, Paolo; Castagné, Raphaële; Chadeau-Hyam, Marc; Botsivali, Maria; Chatziioannou, Aristotelis; Valavanis, Ioannis; Kleinjans, Jos C S; de Kok, Theo M C M; Keun, Hector C; Athersuch, Toby J; Kelly, Rachel; Lenner, Per; Hallmans, Goran; Stephanou, Euripides G; Myridakis, Antonis; Kogevinas, Manolis; Fazzo, Lucia; De Santis, Marco; Comba, Pietro; Bendinelli, Benedetta; Kiviranta, Hannu; Rantakokko, Panu; Airaksinen, Riikka; Ruokojarvi, Paivi; Gilthorpe, Mark; Fleming, Sarah; Fleming, Thomas; Tu, Yu-Kang; Lundh, Thomas; Chien, Kuo-Liong; Chen, Wei J; Lee, Wen-Chung; Kate Hsiao, Chuhsing; Kuo, Po-Hsiu; Hung, Hung; Liao, Shu-Fen

2018-04-18

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10 -4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10 -5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10 -7 ), TGF-α (p = 4.08 × 10 -5 ), fractalkine (p = 1.12 × 10 -3 ), monocyte chemotactic protein-3 (p = 1.36 × 10 -4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10 -4 ) and vascular endothelial growth factor (p = 4.23 × 10 -5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL. © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Associations between DSM-5 section III personality traits and the Minnesota Multiphasic Personality Inventory 2-Restructured Form (MMPI-2-RF) scales in a psychiatric patient sample.

PubMed

Anderson, Jaime L; Sellbom, Martin; Ayearst, Lindsay; Quilty, Lena C; Chmielewski, Michael; Bagby, R Michael

2015-09-01

Our aim in the current study was to evaluate the convergence between Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) Section III dimensional personality traits, as operationalized via the Personality Inventory for DSM-5 (PID-5), and Minnesota Multiphasic Personality Inventory 2-Restructured Form (MMPI-2-RF) scale scores in a psychiatric patient sample. We used a sample of 346 (171 men, 175 women) patients who were recruited through a university-affiliated psychiatric facility in Toronto, Canada. We estimated zero-order correlations between the PID-5 and MMPI-2-RF substantive scale scores, as well as a series of exploratory structural equation modeling (ESEM) analyses to examine how these scales converged in multivariate latent space. Results generally showed empirical convergence between the scales of these two measures that were thematically meaningful and in accordance with conceptual expectations. Correlation analyses showed significant associations between conceptually expected scales, and the highest associations tended to be between scales that were theoretically related. ESEM analyses generated evidence for distinct internalizing, externalizing, and psychoticism factors across all analyses. These findings indicate convergence between these two measures and help further elucidate the associations between dysfunctional personality traits and general psychopathology. (c) 2015 APA, all rights reserved.

Clinical and Biological Predictors of Plasma Levels of Soluble RAGE in Critically Ill Patients: Secondary Analysis of a Prospective Multicenter Observational Study

PubMed Central

Pranal, Thibaut; Pereira, Bruno; Berthelin, Pauline; Roszyk, Laurence; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Gillart, Thierry; Skrzypczak, Yvan; Souweine, Bertrand; Bouvier, Damien; Constantin, Jean-Michel

2018-01-01

Rationale Although soluble forms of the receptor for advanced glycation end products (RAGE) have been recently proposed as biomarkers in multiple acute or chronic diseases, few studies evaluated the influence of usual clinical and biological parameters, or of patient characteristics and comorbidities, on circulating levels of soluble RAGE in the intensive care unit (ICU) setting. Objectives To determine, among clinical and biological parameters that are usually recorded upon ICU admission, which variables, if any, could be associated with plasma levels of soluble RAGE. Methods Data for this ancillary study were prospectively obtained from adult patients with at least one ARDS risk factor upon ICU admission enrolled in a large multicenter observational study. At ICU admission, plasma levels of total soluble RAGE (sRAGE) and endogenous secretory (es)RAGE were measured by duplicate ELISA and baseline patient characteristics, comorbidities, and usual clinical and biological indices were recorded. After univariate analyses, significant variables were used in multivariate, multidimensional analyses. Measurements and Main Results 294 patients were included in this ancillary study, among whom 62% were admitted for medical reasons, including septic shock (11%), coma (11%), and pneumonia (6%). Although some variables were associated with plasma levels of RAGE soluble forms in univariate analysis, multidimensional analyses showed no significant association between admission parameters and baseline plasma sRAGE or esRAGE. Conclusions We found no obvious association between circulating levels of soluble RAGE and clinical and biological indices that are usually recorded upon ICU admission. This trial is registered with NCT02070536. PMID:29861796

The Impact of Hypothyroidism and Heart Failure on Hospitalization Risk.

PubMed

Ro, Kevin; Yuen, Alexander D; Du, Lin; Ro, Clarissa C; Seger, Christian D; Yeh, Michael W; Leung, Angela M; Rhee, Connie M

2018-06-13

Prior studies suggest that the relationship between hypothyroidism and mortality is dependent on underlying cardiovascular risk. Little is known about the association of hypothyroidism with hospitalization risk, and how these associations are modified by cardiovascular status. We examined the association of thyroid status, defined by serum thyrotropin (TSH), with hospitalization risk among patients who received care from a large university-based tertiary care center over 1990-2015. Thyroid status was categorized as hypothyroidism vs. euthyroidism (TSH >4.7 vs. 0.3-4.7mIU/L, respectively). We examined the relationship between thyroid status and hospitalization risk stratified by cardiovascular status using multivariable Cox models. Among 52,856 patients who met eligibility criteria, 49,791 (94.2%) had euthyroidism and 3,065 (5.8%) had hypothyroidism. In analyses stratified by congestive heart failure (CHF) status, compared to euthyroidism, hypothyroidism was associated with higher risk of hospitalization in those with CHF but slightly lower risk in those without CHF (adjusted HRs [aHRs] [95%CI] 1.86 [1.17-2.94] and 0.95 [0.92-0.99], respectively; p-interaction=0.006). In sensitivity analyses accounting for death as a competing event, underlying coronary artery disease (CAD) modified the hypothyroidism-hospitalization relationship, such that stronger associations were observed among those with vs. without CAD. In competing risk analyses, hypothyroidism was associated with higher vs. lower risk of hospitalization among those with vs. without cerebrovascular disease, respectively. Hypothyroidism is associated with higher hospitalization risk among patients with underlying cardiovascular disease. Future studies are needed to determine whether correction of thyroid status with replacement therapy ameliorates hospitalization risk in this population.

Candidate gene association analyses for ketosis resistance in Holsteins.

PubMed

Kroezen, V; Schenkel, F S; Miglior, F; Baes, C F; Squires, E J

2018-06-01

High-yielding dairy cattle are susceptible to ketosis, a metabolic disease that negatively affects the health, fertility, and milk production of the cow. Interest in breeding for more robust dairy cattle with improved resistance to disease is global; however, genetic evaluations for ketosis would benefit from the additional information provided by genetic markers. Candidate genes that are proposed to have a biological role in the pathogenesis of ketosis were investigated in silico and a custom panel of 998 putative single nucleotide polymorphism (SNP) markers was developed. The objective of this study was to test the associations of these new markers with deregressed estimated breeding values (EBV) for ketosis. A sample of 653 Canadian Holstein cows that had been previously genotyped with a medium-density SNP chip were regenotyped with the custom panel. The EBV for ketosis in first and later lactations were obtained for each animal and deregressed for use as pseudo-phenotypes for association analyses. Results of the mixed inheritance model for single SNP association analyses suggested 15 markers in 6 unique candidate genes were associated with the studied trait. Genes encoding proteins involved in metabolic processes, including the synthesis and degradation of fatty acids and ketone bodies, gluconeogenesis, lipid mobilization, and the citric acid cycle, were identified to contain SNP associated with ketosis resistance. This work confirmed the presence of previously described quantitative trait loci for dairy cattle, suggested novel markers for ketosis-resistance, and provided insight into the underlying biology of this disease. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

PubMed

Furet, Elise; El Bouchtaoui, Morad; Feugeas, Jean-Paul; Miquel, Catherine; Leboeuf, Christophe; Beytout, Clémentine; Bertheau, Philippe; Le Rhun, Emilie; Bonneterre, Jacques; Janin, Anne; Bousquet, Guilhem

2017-06-06

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases. Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases. Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series. The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

Investigating shared aetiology between type 2 diabetes and major depressive disorder in a population based cohort.

PubMed

Clarke, Toni-Kim; Obsteter, Jana; Hall, Lynsey S; Hayward, Caroline; Thomson, Pippa A; Smith, Blair H; Padmanabhan, Sandosh; Hocking, Lynne J; Deary, Ian J; Porteous, David J; McIntosh, Andrew M

2017-04-01

Type II diabetes (T2D) and major depressive disorder (MDD) are often co-morbid. The reasons for this co-morbidity are unclear. Some studies have highlighted the importance of environmental factors and a causal relationship between T2D and MDD has also been postulated. In the present study we set out to investigate the shared aetiology between T2D and MDD using Mendelian randomization in a population based sample, Generation Scotland: the Scottish Family Health Study (N = 21,516). Eleven SNPs found to be associated with T2D were tested for association with MDD and psychological distress (General Health Questionnaire scores). We also assessed causality and genetic overlap between T2D and MDD using polygenic risk scores (PRS) assembled from the largest available GWAS summary statistics to date. No single T2D risk SNP was associated with MDD in the MR analyses and we did not find consistent evidence of genetic overlap between MDD and T2D in the PRS analyses. Linkage disequilibrium score regression analyses supported these findings as no genetic correlation was observed between T2D and MDD (rG = 0.0278 (S.E. 0.11), P-value = 0.79). As suggested by previous studies, T2D and MDD covariance may be better explained by environmental factors. Future studies would benefit from analyses in larger cohorts where stratifying by sex and looking more closely at MDD cases demonstrating metabolic dysregulation is possible. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

Work-related stress, inability to relax after work and risk of adult asthma: a population-based cohort study.

PubMed

Loerbroks, A; Gadinger, M C; Bosch, J A; Stürmer, T; Amelang, M

2010-10-01

There is an extensive literature linking stressful work conditions to adverse health outcomes. Notwithstanding, the relationship with asthma has not been examined, although various other measures of psychological stress have been associated with asthma. Therefore, we aimed to investigate the relation between work stress and asthma prevalence and incidence. We used data from a population-based cohort study (n = 5114 at baseline in 1992-1995 and n = 4010 at follow-up in 2002/2003). Asthma was measured by self-reports. Two scales that assessed psychologically adverse work conditions were extracted from a list of work-condition items by factor analysis (these scales were termed 'work stress' and 'inability to relax after work'). For each scale, the derived score was employed both as continuous z-score and as categorized variable in analyses. Associations with asthma were estimated by prevalence ratios (PRs) and risk ratios (RRs) using Poisson regression with a log-link function adjusting for demographics, health-related lifestyles, body mass index and family history of asthma. Analyses were restricted to those in employment (n = 3341). Work stress and inability to relax z-scores were positively associated with asthma prevalence (PR = 1.15, 95%CI = 0.97, 1.36 and PR = 1.43, 95%CI = 1.12, 1.83, respectively). Prospective analyses using z-scores showed that for each 1 standard deviation increase in work stress and inability to relax, the risk of asthma increased by approximately 40% (RR for work stress = 1.46, 95%CI = 1.06, 2.00; RR for inability to relax = 1.39, 95%CI = 1.01, 1.91). Similar patterns of associations were observed in analyses of categorized exposures. This is the first study to show a cross-sectional and longitudinal association of work stress with asthma.

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts.

PubMed

Cai, Yutong; Schikowski, Tamara; Adam, Martin; Buschka, Anna; Carsin, Anne-Elie; Jacquemin, Benedicte; Marcon, Alessandro; Sanchez, Margaux; Vierkötter, Andrea; Al-Kanaani, Zaina; Beelen, Rob; Birk, Matthias; Brunekreef, Bert; Cirach, Marta; Clavel-Chapelon, Françoise; Declercq, Christophe; de Hoogh, Kees; de Nazelle, Audrey; Ducret-Stich, Regina E; Valeria Ferretti, Virginia; Forsberg, Bertil; Gerbase, Margaret W; Hardy, Rebecca; Heinrich, Joachim; Hoek, Gerard; Jarvis, Debbie; Keidel, Dirk; Kuh, Diana; Nieuwenhuijsen, Mark J; Ragettli, Martina S; Ranzi, Andrea; Rochat, Thierry; Schindler, Christian; Sugiri, Dorothea; Temam, Sofia; Tsai, Ming-Yi; Varraso, Raphaëlle; Kauffmann, Francine; Krämer, Ursula; Sunyer, Jordi; Künzli, Nino; Probst-Hensch, Nicole; Hansell, Anna L

2014-11-01

This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. Annual average particulate matter (PM(10), PM(2.5), PM(absorbance), PM(coarse)), NO(2), nitrogen oxides (NO(x)) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for ≥3 months of the year for ≥2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. 15 279 and 10 537 participants respectively were included in the main NO(2) and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO(2) and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PM(coarse) OR 1.31 (1.05 to 1.64) per 5 µg/m(3) increase and PM(10) with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM(2.5abs) (black carbon) exposures. Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations. 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.

Cancer and central nervous system disorders: protocol for an umbrella review of systematic reviews and updated meta-analyses of observational studies.

PubMed

Catalá-López, Ferrán; Hutton, Brian; Driver, Jane A; Page, Matthew J; Ridao, Manuel; Valderas, José M; Alonso-Arroyo, Adolfo; Forés-Martos, Jaume; Martínez, Salvador; Gènova-Maleras, Ricard; Macías-Saint-Gerons, Diego; Crespo-Facorro, Benedicto; Vieta, Eduard; Valencia, Alfonso; Tabarés-Seisdedos, Rafael

2017-04-04

The objective of this study will be to synthesize the epidemiological evidence and evaluate the validity of the associations between central nervous system disorders and the risk of developing or dying from cancer. We will perform an umbrella review of systematic reviews and conduct updated meta-analyses of observational studies (cohort and case-control) investigating the association between central nervous system disorders and the risk of developing or dying from any cancer or specific types of cancer. Searches involving PubMed/MEDLINE, EMBASE, SCOPUS and Web of Science will be used to identify systematic reviews and meta-analyses of observational studies. In addition, online databases will be checked for observational studies published outside the time frames of previous reviews. Eligible central nervous system disorders will be Alzheimer's disease, anorexia nervosa, amyotrophic lateral sclerosis, autism spectrum disorders, bipolar disorder, depression, Down's syndrome, epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and schizophrenia. The primary outcomes will be cancer incidence and cancer mortality in association with a central nervous system disorder. Secondary outcome measures will be site-specific cancer incidence and mortality, respectively. Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles. Data will be abstracted, and study quality/risk of bias will be appraised by two reviewers independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects meta-analyses of primary observational studies will be conducted where appropriate. Parameters for exploring statistical heterogeneity are pre-specified. The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) criteria and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used for determining the quality of evidence for cancer outcomes. Our study will establish the extent of the epidemiological evidence underlying the associations between central nervous system disorders and cancer and will provide a rigorous and updated synthesis of a range of important site-specific cancer outcomes. PROSPERO CRD42016052762.

Association between birthweight and later body mass index: an individual-based pooled analysis of 27 twin cohorts participating in the CODATwins project.

PubMed

Jelenkovic, Aline; Yokoyama, Yoshie; Sund, Reijo; Pietiläinen, Kirsi H; Hur, Yoon-Mi; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Toos C E M; Ooki, Syuichi; Saudino, Kimberly J; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Nelson, Tracy L; Whitfield, Keith E; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Heikkilä, Kauko; Cutler, Tessa L; Hopper, John L; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Burt, S Alexandra; Klump, Kelly L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas Sevenius; Craig, Jeffrey M; Saffery, Richard; Rasmussen, Finn; Tynelius, Per; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Haworth, Claire M A; Plomin, Robert; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Boomsma, Dorret I; Sørensen, Thorkild I A; Kaprio, Jaakko; Silventoinen, Karri

2017-10-01

There is evidence that birthweight is positively associated with body mass index (BMI) in later life, but it remains unclear whether this is explained by genetic factors or the intrauterine environment. We analysed the association between birthweight and BMI from infancy to adulthood within twin pairs, which provides insights into the role of genetic and environmental individual-specific factors. This study is based on the data from 27 twin cohorts in 17 countries. The pooled data included 78 642 twin individuals (20 635 monozygotic and 18 686 same-sex dizygotic twin pairs) with information on birthweight and a total of 214 930 BMI measurements at ages ranging from 1 to 49 years. The association between birthweight and BMI was analysed at both the individual and within-pair levels using linear regression analyses. At the individual level, a 1-kg increase in birthweight was linearly associated with up to 0.9 kg/m2 higher BMI (P < 0.001). Within twin pairs, regression coefficients were generally greater (up to 1.2 kg/m2 per kg birthweight, P < 0.001) than those from the individual-level analyses. Intra-pair associations between birthweight and later BMI were similar in both zygosity groups and sexes and were lower in adulthood. These findings indicate that environmental factors unique to each individual have an important role in the positive association between birthweight and later BMI, at least until young adulthood. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association

Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial

PubMed Central

French, MA; Cozzi-Lepri, A; Arduino, RC; Johnson, M; Achhra, AC; Landay, A

2015-01-01

Background All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin (IL)-6, which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs. Methods Baseline plasma samples from 142 participants enrolled into the SMART study who subsequently died, and 284 matched controls, were assayedfor levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/pro-inflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death. Results Higher plasma levels of pro-inflammatory cytokines (IL-6 and tumour necrosis factor-alpha) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with IL-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of HCV status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group. Conclusions While plasma levels of IL-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs. PMID:25695873

Factors Associated with Women's Antenatal Plans to Use a Baby Walker: A Cross Sectional Study

ERIC Educational Resources Information Center

Illingworth, Rachel; Kendrick, Denise; Collier, Jacqueline; Woods, Amanda; Wattse, Kim; Dewey, Michael; Chen, Chih-Mei

2006-01-01

Objective: The objective of these analyses was to explore maternal antenatal decisions about baby walker use, factors associated with these decisions and the relationship between antenatal plans to use a walker and postnatal walker use. Design: Cross sectional study. Setting: Mothers-to-be (n = 1174) participating in a cluster randomised…

Genome-wide association study based on multiple imputation with low-depth sequencing data: application to biofuel traits in reed canarygrass

USDA-ARS?s Scientific Manuscript database

Genotyping by sequencing allows for large-scale genetic analyses in plant species with no reference genome, but sets the challenge of sound inference in presence of uncertain genotypes. We report an imputation-based genome-wide association study (GWAS) in reed canarygrass (Phalaris arundinacea L., P...

Associations between Finnish 9th Grade Students' School Perceptions, Health Behaviors, and Family Factors

ERIC Educational Resources Information Center

Ilona, Haapasalo; Raili, Valimaa; Lasse, Kannas

2012-01-01

Purpose: The aim of this study was to examine the associations between students' perceptions of the psychosocial school environment, health-compromising behaviours, and selected family factors. The analyses were based on data provided for the Health Behaviour in School-aged Children Study (2006). Design/methodology/approach: The data were obtained…

Hormonal contraception and mental health: results of a population-based study.

PubMed

Toffol, E; Heikinheimo, O; Koponen, P; Luoto, R; Partonen, T

2011-11-01

The effects of oral contraceptives (OCs) on mental health are not clear, and no study has been focused on the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on mental health. The aim of this study was to analyse the association between the use of OCs and the LNG-IUS and psychological well-being and psychopathology. The associations between the current use of OCs and the LNG-IUS, and their duration versus mood symptoms [Beck Depression Inventory (BDI)], psychological well-being [(General Health Questionnaire-12 (GHQ-12)] and recent psychiatric diagnoses [(Composite International Diagnostic Interview (CIDI)] were examined among women who participated in the Finnish-population-based Health 2000 study. Analyses were performed on the 30- to 54-year-old sample (n = 2310); some of the analyses were extended to include the younger age group (18- to 54-year-old sample; n = 3223). Overall, hormonal contraception was well tolerated with few significant effects on psychological well-being. The length of OC use was inversely associated with some BDI items ('dissatisfaction, irritability, lost interest in people, earlier waking and lost interest in sex'), and directly associated with 'worries about one's health' (BDI) and with a current diagnosis of 'alcohol dependence' (CIDI). The current use of the LNG-IUS was inversely associated with 'earlier waking' (BDI) and with 'impaired concentration' (GHQ), while the length of LNG-IUS use was inversely associated with 'strain' (GHQ). The influence of hormonal birth control on mental health is modest and mainly favourable. The length of current OC use seems to have some beneficial effects on mood although the longer the duration of use, the greater the association with a diagnosis of alcohol dependence. Knowledge of the use of hormonal contraception might be of value when assessing psychopathology in women. The cross-sectional design, with partly retrospective data collection, precludes any causal conclusions.

Motivation factors for suicidal behavior and their clinical relevance in admitted psychiatric patients.

PubMed

Hayashi, Naoki; Igarashi, Miyabi; Imai, Atsushi; Yoshizawa, Yuka; Asamura, Kaori; Ishikawa, Yoichi; Tokunaga, Taro; Ishimoto, Kayo; Tatebayashi, Yoshitaka; Harima, Hirohiko; Kumagai, Naoki; Ishii, Hidetoki; Okazaki, Yuji

2017-01-01

Suicidal behavior (SB) is a major, worldwide health concern. To date there is limited understanding of the associated motivational aspects which accompany this self-initiated conduct. To develop a method for identifying motivational features associated with SB by studying admitted psychiatric patients, and to examine their clinical relevance. By performing a factor analytic study using data obtained from a patient sample exhibiting high suicidality and a variety of SB methods, Motivations for SB Scale (MSBS) was constructed to measure the features. Data included assessments of DSM-IV psychiatric and personality disorders, suicide intent, depressive symptomatology, overt aggression, recent life events (RLEs) and methods of SB, collated from structured interviews. Association of identified features with clinical variables was examined by correlation analyses and MANCOVA. Factor analyses elicited a 4-factor solution composed of Interpersonal-testing (IT), Interpersonal-change (IC), Self-renunciation (SR) and Self-sustenance (SS). These factors were classified according to two distinctions, namely interpersonal vs. intra-personal directedness, and the level of assumed influence by SB or the relationship to prevailing emotions. Analyses revealed meaningful links between patient features and clinical variables. Interpersonal-motivations (IT and IC) were associated with overt aggression, low suicidality and RLE discord or conflict, while SR was associated with depression, high suicidality and RLE separation or death. Borderline personality disorder showed association with IC and SS. When self-strangulation was set as a reference SB method, self-cutting and overdose-taking were linked to IT and SS, respectively. The factors extracted in this study largely corresponded to factors from previous studies, implying that they may be useful in a wider clinical context. The association of these features with SB-related factors suggests that they constitute an integral part of the process leading to SB. These results provide a base for further research into clinical strategies for patient management and therapy.

A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer

PubMed Central

2010-01-01

Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer. PMID:21044319

Symptoms and the use of wireless communication devices: A prospective cohort study in Swiss adolescents

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

Schoeni, Anna, E-mail: anna.schoeni@unibas.ch

Background: We investigated whether radiofrequency electromagnetic fields (RF-EMF) from mobile phones and other wireless devices or by the wireless device use itself due to non-radiation related factors in that context are associated with an increase in health symptom reports of adolescents in Central Switzerland. Methods: In a prospective cohort study, 439 study participants (participation rate: 36.8%) aged 12–17 years, completed questionnaires about their mobile and cordless phone use, their self-reported symptoms and possible confounding factors at baseline (2012/2013) and one year later (2013/2014). Operator recorded mobile phone data was obtained for a subgroup of 234 adolescents. RF-EMF dose measures consideringmore » various factors affecting RF-EMF exposure were computed for the brain and the whole body. Data were analysed using a mixed-logistic cross-sectional model and a cohort approach, where we investigated whether cumulative dose over one year was related to a new onset of a symptom between baseline and follow-up. All analyses were adjusted for relevant confounders. Results: Participation rate in the follow-up was 97% (425 participants). In both analyses, cross-sectional and cohort, various symptoms tended to be mostly associated with usage measures that are only marginally related to RF-EMF exposure such as the number of text messages sent per day (e.g. tiredness: OR:1.81; 95%CI:1.20–2.74 for cross-sectional analyses and OR:1.87; 95%CI:1.04–3.38 for cohort analyses). Outcomes were generally less strongly or not associated with mobile phone call duration and RF-EMF dose measures. Conclusions: Stronger associations between symptoms of ill health and wireless communication device use than for RF-EMF dose measures were observed. Such a result pattern does not support a causal association between RF-EMF exposure and health symptoms of adolescents but rather suggests that other aspects of extensive media use are related to symptoms. - Highlights: • This is a prospective cohort study with approximately one year of follow-up. • Self-reported and operator recorded mobile phone use data were collected. • The cumulative RF-EMF dose for the brain and for the whole body was calculated. • Associations were stronger for the use of wireless devices than for RF-EMF dose. • This suggests that rather aspects of extensive media use than RF-EMF are related to symptoms.« less

Child maltreatment and adult criminal behavior: does criminal thinking explain the association?

PubMed

Cuadra, Lorraine E; Jaffe, Anna E; Thomas, Renu; DiLillo, David

2014-08-01

Criminal thinking styles were examined as mediational links between different forms of child maltreatment (i.e., sexual abuse, physical abuse, and physical neglect) and adult criminal behaviors in 338 recently adjudicated men. Analyses revealed positive associations between child sexual abuse and sexual offenses as an adult, and between child physical abuse/neglect and endorsing proactive and reactive criminal thinking styles. Mediation analyses showed that associations between overall maltreatment history and adult criminal behaviors were accounted for by general criminal thinking styles and both proactive and reactive criminal thinking. These findings suggest a potential psychological pathway to criminal behavior associated with child maltreatment. Limitations of the study as well as research and clinical implications of the results are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Below the poverty line and non-communicable diseases in Kerala: The Epidemiology of Non-communicable Diseases in Rural Areas (ENDIRA) study.

PubMed

Menon, Jaideep; Vijayakumar, N; Joseph, Joseph K; David, P C; Menon, M N; Mukundan, Shyam; Dorphy, P D; Banerjee, Amitava

2015-01-01

India carries the greatest burden of global non-communicable diseases (NCDs). Poverty is strongly associated with NCDs but there are few prevalence studies which have measured poverty in India, particularly in rural settings. In Kerala, India, a population of 113,462 individuals was identified. The "Epidemiology of Non-communicable Diseases in Rural Areas" (ENDIRA) study was conducted via ASHAs (Accredited Social Health Activists). Standardised questionnaires were used in household interviews of individuals ≥18years during 2012 to gather sociodemographic, lifestyle and medical data for this population. The Government of Kerala definition of "the poverty line" was used. The association between below poverty line (BPL) status, NCDs and risk factors was analysed in multivariable regression models. 84,456 adults were included in the analyses (25.4% below the poverty line). The prevalence of NCDs was relatively common: myocardial infarction (MI) 1.4%, stroke 0.3%, respiratory diseases 5.0%, and cancer 1.1%. BPL status was not associated with age (p=0.96) or gender (p=0.26). Compared with those above the poverty line (APL), the BPL group was less likely to have diabetes, hypertension or dyslipidaemia (p<0.0001), and more likely to smoke (p<0.0001). Compared with APL, BPL was associated with stroke (OR 1.33, 1.04-1.69; p=0.02) and respiratory disease (OR 1.23, 1.15-1.32; p<0.0001) in multivariable analyses, but not MI or cancer. In rural Kerala, BPL status was associated with stroke and respiratory diseases, but not with MI and cancer although it was associated with smoking status, compared with above poverty line status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2.

PubMed

Winham, S J; Cuellar-Barboza, A B; Oliveros, A; McElroy, S L; Crow, S; Colby, C; Choi, D-S; Chauhan, M; Frye, M; Biernacka, J M

2014-09-01

Bipolar disorder (BD) is associated with higher body mass index (BMI) and increased metabolic comorbidity. Considering the associated phenotypic traits in genetic studies of complex diseases, either by adjusting for covariates or by investigating interactions between genetic variants and covariates, may help to uncover the missing heritability. However, obesity-related traits have not been incorporated in prior genome-wide analyses of BD as covariates or potential interacting factors. To investigate the genetic factors underlying BD while considering BMI, we conducted genome-wide analyses using data from the Genetic Association Information Network BD study. We analyzed 729,454 genotyped single-nucleotide polymorphism (SNP) markers on 388 European-American BD cases and 1020 healthy controls with available data for maximum BMI. We performed genome-wide association analyses of the genetic effects while accounting for the effect of maximum BMI, and also evaluated SNP-BMI interactions. A joint test of main and interaction effects demonstrated significant evidence of association at the genome-wide level with rs12772424 in an intron of TCF7L2 (P=2.85E-8). This SNP exhibited interaction effects, indicating that the bipolar susceptibility risk of this SNP is dependent on BMI. TCF7L2 codes for the transcription factor TCF/LF, part of the Wnt canonical pathway, and is one of the strongest genetic risk variants for type 2 diabetes (T2D). This is consistent with BD pathophysiology, as the Wnt pathway has crucial implications in neurodevelopment, neurogenesis and neuroplasticity, and is involved in the mechanisms of action of BD and depression treatments. We hypothesize that genetic risk for BD is BMI dependent, possibly related to common genetic risk with T2D.

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 neighborhood deprivation was associated with decreasing participation. This suggests the need to develop preventive health checks tailored to deprived neighborhoods.

Factors associated with patient satisfaction with primary care in Europe: results from the EUprimecare project.

PubMed

Sánchez-Piedra, Carlos Alberto; Prado-Galbarro, Francisco Javier; García-Pérez, Sonia; Santamera, Antonio Sarría

2014-01-01

EUprimecare is a study funded by the Seventh Framework Programme of the European Union, aimed at analysing the quality of the different models of primary care in Europe. The objective of this study was to describe and analyse the determinants associated with patient satisfaction in primary care in Europe. We conducted telephone population surveys among primary care users in each EUprimecare consortium country (Germany, Spain, Estonia, Finland, Hungary, Italy and Lithuania). The survey was conducted with 3020 patients and the questionnaire included sociodemographic variables, health status, and use and satisfaction with primary care services. We undertook descriptive analyses, bivariate correlations and an ordinal regression model to study the direct relationship between levels of satisfaction and the explanatory variables for demographics, health status and health services for patients. We present the regression coefficients (β) with 95% confidence intervals and associated tests of statistical significance. The mean age of the respondents was 51 years (SD 14.1). We found significant associations between the level of satisfaction and age (β = 0.008), specialist visits (β = -0.030), not having a general practitioner (β = 0.70), not measuring weight, cholesterol and blood pressure (β = 0.52), country (β1 Germany = -1.08 and β2 Lithuania = -0.60; β3 Hungary = 0.50 and β4 Italy = 0.53) and a better perception of health status (β = 0.33). Specialist visits had a negative association with satisfaction. Overall, the results indicate factors that may be related to greater satisfaction with primary care services: age, visits to a specialist, having a doctor assigned to primary care and measurement of control parameters are associated with a better perception of the care received.

Using linked educational attainment data to reduce bias due to missing outcome data in estimates of the association between the duration of breastfeeding and IQ at 15 years.

PubMed

Cornish, Rosie P; Tilling, Kate; Boyd, Andy; Davies, Amy; Macleod, John

2015-06-01

Most epidemiological studies have missing information, leading to reduced power and potential bias. Estimates of exposure-outcome associations will generally be biased if the outcome variable is missing not at random (MNAR). Linkage to administrative data containing a proxy for the missing study outcome allows assessment of whether this outcome is MNAR and the evaluation of bias. We examined this in relation to the association between infant breastfeeding and IQ at 15 years, where a proxy for IQ was available through linkage to school attainment data. Subjects were those who enrolled in the Avon Longitudinal Study of Parents and Children in 1990-91 (n = 13 795), of whom 5023 had IQ measured at age 15. For those with missing IQ, 7030 (79%) had information on educational attainment at age 16 obtained through linkage to the National Pupil Database. The association between duration of breastfeeding and IQ was estimated using a complete case analysis, multiple imputation and inverse probability-of-missingness weighting; these estimates were then compared with those derived from analyses informed by the linkage. IQ at 15 was MNAR-individuals with higher attainment were less likely to have missing IQ data, even after adjusting for socio-demographic factors. All the approaches underestimated the association between breastfeeding and IQ compared with analyses informed by linkage. Linkage to administrative data containing a proxy for the outcome variable allows the MNAR assumption to be tested and more efficient analyses to be performed. Under certain circumstances, this may produce unbiased results. © The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.

The Fanconi anemia family of genes and its correlation with breast cancer susceptibility and breast cancer features.

PubMed

Barroso, E; Pita, G; Arias, J I; Menendez, P; Zamora, P; Blanco, M; Benitez, J; Ribas, G

2009-12-01

Fanconi anemia (FA) family of proteins participates in the DNA repair pathway by homologous recombination, and it is currently formed by 13 genes. Some of these proteins also confer susceptibility to hereditary breast and ovarian cancer (HBOC), since FANCD1 is the BRCA2 breast cancer susceptibility gene, and FANCN/PALB2 and FANCJ/BRIP1 explain 2% of non-BRCA1/2 HBOC families. Thus, there is an important connection between FA and BRCA pathways. In a previous case-control association study analysing FANCA, FANCD2 and FANCL, we reported an association between FANCD2 and sporadic breast cancer (BC) risk (OR = 1.35). In order to know whether variants in other FA genes could also be involved in this association, we have extended our study with the rest of FA genes and some others implicated in the BRCA pathway. We have also analyzed the correlation with survival, nodal metastasis and hormonal receptors (ER- and PR-). A total of 61 SNPs in ten FA genes (FANC-B, -C, -D1, -E, -F, -G, -I, -J, -M, -N) and five FA related genes (ATM, ATR, BRCA1, H2AX and USP1) were studied in a total of 547 consecutive and nonrelated sporadic BC cases and 552 unaffected controls from the Spanish population. Association analyses reported marginal statistically significant results with the minor allele of intronic SNPs in three genes: BRCA1, BRCA2/FANCD1, and ATM. Survival association with SNPs on FANCC and BRCA2/FANCD1 genes were also reported. Sub-group analyses revealed associations between SNPs on FANCI and ATM and nodal metastasis status and between FANCJ/BRIP1 and FANCN/PALB2 and PR- status.

Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis.

PubMed

Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan

2017-04-01

non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001). Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

Association between circulating irisin and insulin resistance in non-diabetic adults: A meta-analysis.

PubMed

Qiu, Shanhu; Cai, Xue; Yin, Han; Zügel, Martina; Sun, Zilin; Steinacker, Jürgen Michael; Schumann, Uwe

2016-06-01

Exogenous administration of recombinant irisin improves glucose metabolism. However, the association of endogenous circulating (plasma/serum) irisin with insulin resistance remains poorly delineated. This study was aimed to examine this association by meta-analyzing the current evidence without study design restriction in non-diabetic adults. Peer-reviewed studies written in English from 3 databases were searched to December 2015. Studies that reported the association between circulating irisin and insulin resistance (or its reverse, insulin sensitivity) in non-diabetic non-pregnant adults (mean ages ≥18years) were included. The pooled correlation coefficient (r) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. Of the 195 identified publications, 17 studies from 15 articles enrolling 1912 participants reported the association between circulating irisin and insulin resistance. The pooled effect size was 0.15 (95% CI: 0.07 to 0.22) with a substantial heterogeneity (I(2)=55.5%). This association seemed to be modified by glycemic status (fasting blood glucose ≥6.1mmol/L versus <6.1mmol/L) and racial-ethnic difference (Asians versus Europeans versus Americans), but not by sex difference, sampling time-point, blood sample type, ELISA kits used, baseline age, or body mass index. Circulating irisin was inversely associated with insulin sensitivity (6 studies; r=-0.17, 95% CI: -0.25 to -0.09). Circulating irisin is directly and positively associated with insulin resistance in non-diabetic adults. However, this association is rather small and requires further clarification, in particular by well-designed large epidemiological studies with overall, race-, and sex-specific analyses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Meta-Analysis in Genome-Wide Association Datasets: Strategies and Application in Parkinson Disease

PubMed Central

Evangelou, Evangelos; Maraganore, Demetrius M.; Ioannidis, John P.A.

2007-01-01

Background Genome-wide association studies hold substantial promise for identifying common genetic variants that regulate susceptibility to complex diseases. However, for the detection of small genetic effects, single studies may be underpowered. Power may be improved by combining genome-wide datasets with meta-analytic techniques. Methodology/Principal Findings Both single and two-stage genome-wide data may be combined and there are several possible strategies. In the two-stage framework, we considered the options of (1) enhancement of replication data and (2) enhancement of first-stage data, and then, we also considered (3) joint meta-analyses including all first-stage and second-stage data. These strategies were examined empirically using data from two genome-wide association studies (three datasets) on Parkinson disease. In the three strategies, we derived 12, 5, and 49 single nucleotide polymorphisms that show significant associations at conventional levels of statistical significance. None of these remained significant after conservative adjustment for the number of performed analyses in each strategy. However, some may warrant further consideration: 6 SNPs were identified with at least 2 of the 3 strategies and 3 SNPs [rs1000291 on chromosome 3, rs2241743 on chromosome 4 and rs3018626 on chromosome 11] were identified with all 3 strategies and had no or minimal between-dataset heterogeneity (I2 = 0, 0 and 15%, respectively). Analyses were primarily limited by the suboptimal overlap of tested polymorphisms across different datasets (e.g., only 31,192 shared polymorphisms between the two tier 1 datasets). Conclusions/Significance Meta-analysis may be used to improve the power and examine the between-dataset heterogeneity of genome-wide association studies. Prospective designs may be most efficient, if they try to maximize the overlap of genotyping platforms and anticipate the combination of data across many genome-wide association studies. PMID:17332845

Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study

PubMed Central

Brunner, Clair; Davies, Neil M.; Martin, Richard M.; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Donovan, Jenny; Hamdy, Freddie C.; Pashayan, Nora; Khaw, Kay‐Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R.; Pandha, Hardev

2016-01-01

Prostate cancer is the most common cancer in men in developed countries, and is a target for risk reduction strategies. The effects of alcohol consumption on prostate cancer incidence and survival remain unclear, potentially due to methodological limitations of observational studies. In this study, we investigated the associations of genetic variants in alcohol‐metabolising genes with prostate cancer incidence and survival. We analysed data from 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. Study‐specific associations of 68 single nucleotide polymorphisms (SNPs) in 8 alcohol‐metabolising genes (Alcohol Dehydrogenases (ADHs) and Aldehyde Dehydrogenases (ALDHs)) with prostate cancer diagnosis and prostate cancer‐specific mortality, by grade, were assessed using logistic and Cox regression models, respectively. The data across the 25 studies were meta‐analysed using fixed‐effect and random‐effects models. We found little evidence that variants in alcohol metabolising genes were associated with prostate cancer diagnosis. Four variants in two genes exceeded the multiple testing threshold for associations with prostate cancer mortality in fixed‐effect meta‐analyses. SNPs within ALDH1A2 associated with prostate cancer mortality were rs1441817 (fixed effects hazard ratio, HRfixed = 0.78; 95% confidence interval (95%CI):0.66,0.91; p values = 0.002); rs12910509, HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.003); and rs8041922 (HRfixed = 0.76; 95%CI:0.64,0.91; p values = 0.002). These SNPs were in linkage disequilibrium with each other. In ALDH1B1, rs10973794 (HRfixed = 1.43; 95%CI:1.14,1.79; p values = 0.002) was associated with prostate cancer mortality in men with low‐grade prostate cancer. These results suggest that alcohol consumption is unlikely to affect prostate cancer incidence, but it may influence disease progression. PMID:27643404

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. © Copyright 2017 Physicians Postgraduate Press, Inc.

Relationships between optimism, educational environment, career adaptability and career motivation in nursing undergraduates: A cross-sectional study.

PubMed

Fang, Wenjie; Zhang, Yanting; Mei, Jiaojiao; Chai, Xiaohui; Fan, Xiuzhen

2018-06-01

For solving the problem of the abandonment of the career in nursing undergraduates, it is important to understand their motivation to choose nursing as a career and its associated personal and situational factors. To examine the relationships between optimism, educational environment, career adaptability, and career motivation in nursing undergraduates using the career construction model of adaptation. This study adopted a cross-sectional design. A convenience sample of 1060 nursing undergraduates from three universities completed questionnaires for measuring optimism, educational environment, career adaptability, and career motivation. Confirmatory factor analyses, descriptive analyses, comparison analyses, correlation analyses, and mediation analyses were performed accordingly. Nursing undergraduates' career motivation was positively correlated with their career adaptability (r = 0.41, P < 0.01), the educational environment (r = 0.60, P < 0.01), and optimism (r = 0.26, P < 0.01). In addition, the effects of optimism and educational environment on career motivation were partially mediated by career adaptability in nursing undergraduates. In nursing undergraduates, the educational environment had a relatively strong positive association with career motivation, while optimism had a weak one. Career adaptability played a mediating role in the relationships. Targeted interventions may improve nursing undergraduates' career motivation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Genome-wide association studies and epistasis analyses of candidate genes related to age at menarche and age at natural menopause in a Korean population.

PubMed

Pyun, Jung-A; Kim, Sunshin; Cho, Nam H; Koh, InSong; Lee, Jong-Young; Shin, Chol; Kwack, KyuBum

2014-05-01

The aim of this study was to identify polymorphisms and gene-gene interactions that are significantly associated with age at menarche and age at menopause in a Korean population. A total of 3,452 and 1,827 women participated in studies of age at menarche and age at natural menopause, respectively. Linear regression analyses adjusted for residence area were used to perform genome-wide association studies (GWAS), candidate gene association studies, and interactions between the candidate genes for age at menarche and age at natural menopause. In GWAS, four single nucleotide polymorphisms (SNPs; rs7528241, rs1324329, rs11597068, and rs6495785) were strongly associated with age at natural menopause (lowest P = 9.66 × 10). However, GWAS of age at menarche did not reveal any strong associations. In candidate gene association studies, SNPs with P < 0.01 were selected to test their synergistic interactions. For age at natural menopause, there was a significant interaction between intronic SNPs on ADAM metallopeptidase with thrombospondin type I motif 9 (ADAMTS9) and SMAD family member 3 (SMAD3) genes (P = 9.52 × 10). For age at menarche, there were three significant interactions between three intronic SNPs on follicle-stimulating hormone receptor (FSHR) gene and one SNP located at the 3' flanking region of insulin-like growth factor 2 receptor (IGF2R) gene (lowest P = 1.95 × 10). Novel SNPs and synergistic interactions between candidate genes are significantly associated with age at menarche and age at natural menopause in a Korean population.

A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked Traits.

PubMed

Asimit, Jennifer L; Panoutsopoulou, Kalliope; Wheeler, Eleanor; Berndt, Sonja I; Cordell, Heather J; Morris, Andrew P; Zeggini, Eleftheria; Barroso, Inês

2015-12-01

Diseases often cooccur in individuals more often than expected by chance, and may be explained by shared underlying genetic etiology. A common approach to genetic overlap analyses is to use summary genome-wide association study data to identify single-nucleotide polymorphisms (SNPs) that are associated with multiple traits at a selected P-value threshold. However, P-values do not account for differences in power, whereas Bayes' factors (BFs) do, and may be approximated using summary statistics. We use simulation studies to compare the power of frequentist and Bayesian approaches with overlap analyses, and to decide on appropriate thresholds for comparison between the two methods. It is empirically illustrated that BFs have the advantage over P-values of a decreasing type I error rate as study size increases for single-disease associations. Consequently, the overlap analysis of traits from different-sized studies encounters issues in fair P-value threshold selection, whereas BFs are adjusted automatically. Extensive simulations show that Bayesian overlap analyses tend to have higher power than those that assess association strength with P-values, particularly in low-power scenarios. Calibration tables between BFs and P-values are provided for a range of sample sizes, as well as an approximation approach for sample sizes that are not in the calibration table. Although P-values are sometimes thought more intuitive, these tables assist in removing the opaqueness of Bayesian thresholds and may also be used in the selection of a BF threshold to meet a certain type I error rate. An application of our methods is used to identify variants associated with both obesity and osteoarthritis. © 2015 The Authors. *Genetic Epidemiology published by Wiley Periodicals, Inc.

Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis

PubMed Central

Bjørngaard, Johan H; Nordestgaard, Ask Tybjærg; Taylor, Amy E; Treur, Jorien L; Gabrielsen, Maiken E; Munafò, Marcus R; Nordestgaard, Børge Grønne; Åsvold, Bjørn Olav; Romundstad, Pål; Davey Smith, George

2017-01-01

Abstract Background There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods We performed Mendelian randomization analyses in the UK Biobank (N = 114 029), the Norwegian HUNT study (N = 56 664) and the Copenhagen General Population Study (CGPS) (N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results Each additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI: 0.03, 0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI: −0.002, 0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.16 cups per day, 95% CI: 0.11, 0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI: -0.01, 0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers or that the coffee-related variants were associated with cigarette consumption. Conclusions Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking. PMID:29025033

Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study

PubMed Central

Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G.; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

2010-01-01

Context: Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Objective: Our objective was to evaluate the association between organic nitrates and hip fracture risk. Methods: A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991–2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Results: Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83–1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63–1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97–1.40). No association was found between duration of nitrate use and fracture risk. Conclusions: Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects. PMID:20130070

A Systematic Review and Meta-Analysis of a Measure of Staff/Child Interaction Quality (the Classroom Assessment Scoring System) in Early Childhood Education and Care Settings and Child Outcomes.

PubMed

Perlman, Michal; Falenchuk, Olesya; Fletcher, Brooke; McMullen, Evelyn; Beyene, Joseph; Shah, Prakesh S

2016-01-01

The quality of staff/child interactions as measured by the Classroom Assessment Scoring System (CLASS) in Early Childhood Education and Care (ECEC) programs is thought to be important for children's outcomes. The CLASS is made of three domains that assess Emotional Support, Classroom Organization and Instructional Support. It is a relatively new measure that is being used increasingly for research, quality monitoring/accountability and other applied purposes. Our objective was to evaluate the association between the CLASS and child outcomes. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were conducted up to July 3, 2015. Studies that measured association between the CLASS and child outcomes for preschool-aged children who attended ECEC programs were included after screening by two independent reviewers. Searches and data extraction were conducted by two independent reviewers. Thirty-five studies were systematically reviewed of which 19 provided data for meta-analyses. Most studies had moderate to high risk of bias. Of the 14 meta-analyses we conducted, associations between Classroom Organization and Pencil Tapping and between Instructional Support and SSRS Social Skills were significant with pooled correlations of .06 and .09 respectively. All associations were in the expected direction. In the systematic review, significant correlations were reported mainly from one large dataset. Substantial heterogeneity in use of the CLASS, its dimensions, child outcomes and statistical measures was identified. Greater consistency in study methodology is urgently needed. Given the multitude of factors that impact child development it is encouraging that our analyses revealed some, although small, associations between the CLASS and children's outcomes.

Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study.

PubMed

Moreno-López, Laura; Stamatakis, Emmanuel A; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

2012-01-01

Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients.

Patient-reported safety incidents in older patients with long-term conditions: a large cross-sectional study

PubMed Central

Panagioti, Maria; Blakeman, Thomas; Hann, Mark; Bower, Peter

2017-01-01

Background Increasing evidence suggests that patient safety is a serious concern for older patients with long-term conditions. Despite this, there is a lack of research on safety incidents encountered by this patient group. In this study, we sought to examine patient reports of safety incidents and factors associated with reports of safety incidents in older patients with long-term conditions. Methods The baseline cross-sectional data from a longitudinal cohort study were analysed. Older patients (n=3378 aged 65 years and over) with a long-term condition registered in general practices were included in the study. The main outcome was patient-reported safety incidents including availability and appropriateness of medical tests and prescription of wrong types or doses of medication. Binary univariate and multivariate logistic regression analyses were undertaken to examine factors associated with patient-reported safety incidents. Results Safety incidents were reported by 11% of the patients. Four factors were significantly associated with patient-reported safety incidents in multivariate analyses. The experience of multiple long-term conditions (OR=1.09, 95% CI 1.05 to 1.13), a probable diagnosis of depression (OR=1.36, 95% CI 1.06 to 1.74) and greater relational continuity of care (OR=1.28, 95% CI 1.08 to 1.52) were associated with increased odds for patient-reported safety incidents. Perceived greater support and involvement in self-management was associated with lower odds for patient-reported safety incidents (OR=0.95, 95% CI 0.93 to 0.97). Conclusions We found that older patients with multimorbidity and depression are more likely to report experiences of patient safety incidents. Improving perceived support and involvement of patients in their care may help prevent patient-reported safety incidents. PMID:28559454

Use of organic nitrates and the risk of hip fracture: a population-based case-control study.

PubMed

Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

2010-04-01

Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Our objective was to evaluate the association between organic nitrates and hip fracture risk. A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk. Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.

A Systematic Review and Meta-Analysis of a Measure of Staff/Child Interaction Quality (the Classroom Assessment Scoring System) in Early Childhood Education and Care Settings and Child Outcomes

PubMed Central

Perlman, Michal; Falenchuk, Olesya; Fletcher, Brooke; McMullen, Evelyn; Beyene, Joseph; Shah, Prakesh S.

2016-01-01

The quality of staff/child interactions as measured by the Classroom Assessment Scoring System (CLASS) in Early Childhood Education and Care (ECEC) programs is thought to be important for children’s outcomes. The CLASS is made of three domains that assess Emotional Support, Classroom Organization and Instructional Support. It is a relatively new measure that is being used increasingly for research, quality monitoring/accountability and other applied purposes. Our objective was to evaluate the association between the CLASS and child outcomes. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were conducted up to July 3, 2015. Studies that measured association between the CLASS and child outcomes for preschool-aged children who attended ECEC programs were included after screening by two independent reviewers. Searches and data extraction were conducted by two independent reviewers. Thirty-five studies were systematically reviewed of which 19 provided data for meta-analyses. Most studies had moderate to high risk of bias. Of the 14 meta-analyses we conducted, associations between Classroom Organization and Pencil Tapping and between Instructional Support and SSRS Social Skills were significant with pooled correlations of .06 and .09 respectively. All associations were in the expected direction. In the systematic review, significant correlations were reported mainly from one large dataset. Substantial heterogeneity in use of the CLASS, its dimensions, child outcomes and statistical measures was identified. Greater consistency in study methodology is urgently needed. Given the multitude of factors that impact child development it is encouraging that our analyses revealed some, although small, associations between the CLASS and children’s outcomes. PMID:28036333

Risk factors associated with asbestos-related diseases: a community-based case-control study.

PubMed

Rosell-Murphy, Magdalena-Isabel; Abós-Herràndiz, Rafael; Olivella, Josep Tarrés; Alberti-Casas, Constança; Allas, Isabel García; Artés, Xavier Martinez; Günther, Ilona Krier; Malet, Isidre Grimau; Martínez, Ramon Orriols; Canela-Soler, Jaume

2013-08-06

Asbestos is a first level carcinogen. However, few epidemiological studies analyse the risk and protective factors associated with asbestos-related diseases and follow up these conditions in the general population. Pleural mesothelioma, caused by inhalation of asbestos fibres at work, at home or in the environment, is the most representative asbestos-related disease.The objectives of this study are to analyse the risk and protective factors associated with asbestos-related diseases and to investigate the incidence of new clinical manifestations in patients already diagnosed with some form of ARD. We have designed a matched case-control study with follow up of both cohorts from a population of a health district of the Barcelona province that has been exposed to asbestos for a period of 90 years. A better understanding of asbestos-related diseases should improve i) the clinical and epidemiological follow up of patients with this condition; ii) the design of new treatment strategies; iii) and the development of preventive activities. At the end of the study, the two cohorts created in this study (affected cases and healthy controls) will constitute the basis for future research.

How are Closeness and Conflict in Student-Teacher Relationships Associated with Demographic Factors, School Functioning and Mental Health in Norwegian Schoolchildren Aged 6-13?

ERIC Educational Resources Information Center

Drugli, May Britt

2013-01-01

This study explored the association between teacher-reported student-teacher relationship quality (closeness and conflict) and demographic factors, school functioning and child mental health in a cross-sectional study. The study was conducted among a national sample of Norwegian school children (N?=?825) in grades 1 to 7. Bivariate analyses and…

Different indicators of socioeconomic status and their relative importance as determinants of health in old age.

PubMed

Darin-Mattsson, Alexander; Fors, Stefan; Kåreholt, Ingemar

2017-09-26

Socioeconomic status has been operationalised in a variety of ways, most commonly as education, social class, or income. In this study, we also use occupational complexity and a SES-index as alternative measures of socioeconomic status. Studies show that in analyses of health inequalities in the general population, the choice of indicators influence the magnitude of the observed inequalities. Less is known about the influence of indicator choice in studies of older adults. The aim of this study is twofold: i) to analyse the impact of the choice of socioeconomic status indicator on the observed health inequalities among older adults, ii) to explore whether different indicators of socioeconomic status are independently associated with health in old age. We combined data from two nationally representative Swedish surveys, providing more than 20 years of follow-up. Average marginal effects were estimated to compare the association between the five indicators of SES, and three late-life health outcomes: mobility limitations, limitations in activities of daily living (ADL), and psychological distress. All socioeconomic status indicators were associated with late-life health; there were only minor differences in the effect sizes. Income was most strongly associated to all indicators of late-life health, the associations remained statistically significant when adjusting for the other indicators. In the fully adjusted models, education contributed to the model fits with 0-3% (depending on the outcome), social class with 0-1%, occupational complexity with 1-8%, and income with 3-18%. Our results indicate overlapping properties between socioeconomic status indicators in relation to late-life health. However, income is associated to late-life health independently of all other variables. Moreover, income did not perform substantially worse than the composite SES-index in capturing health variation. Thus, if the primary objective of including an indicator of socioeconomic status is to adjust the model for socioeconomic differences in late-life health rather than to analyse these inequalities per se, income may be the preferable indicator. If, on the other hand, the primary objective of a study is to analyse specific aspects of health inequalities, or the mechanisms that drive health inequalities, then the choice of indicator should be theoretically guided.

Buffering effect of workplace social capital on the association of job insecurity with psychological distress in Japanese employees: a cross-sectional study.

PubMed

Inoue, Akiomi; Kawakami, Norito; Eguchi, Hisashi; Tsutsumi, Akizumi

2016-09-30

The present study aimed to examine the buffering effect of workplace social capital (WSC) on the association of job insecurity with psychological distress in Japanese employees. 2,971 employees from two factories of a manufacturing company in Japan completed a self-administered questionnaire including the scales on job insecurity, WSC, psychological distress, demographic and occupational characteristics, and quantitative workload. Using psychological distress (defined as a total score of the K6 scale ≥5) as a dependent variable, multiple logistic regression analyses were conducted. In a series of analyses, interaction term of job insecurity×WSC was included in the model. After adjusting for demographic and occupational characteristics as well as for quantitative workload and interaction effect of quantitative workload×WSC, high job insecurity and low WSC were significantly associated with psychological distress. Furthermore, a significant interaction effect of job insecurity×WSC was observed. Specifically, the association of job insecurity with psychological distress was greater among those who perceived lower levels of WSC (prevalence odds ratio=3.79 [95% confidence interval=2.70-5.32] for high vs. low job insecurity subgroup) than among those who perceived higher levels of WSC (prevalence odds ratio=2.96 [95% confidence interval=2.19-4.01] for high vs. low job insecurity subgroup). These findings were replicated among permanent male employees in the gender-stratified analyses. The present study suggests that WSC has a buffering effect on the association of job insecurity with psychological distress at least among Japanese permanent male employees.

Buffering effect of workplace social capital on the association of job insecurity with psychological distress in Japanese employees: a cross-sectional study

PubMed Central

Inoue, Akiomi; Kawakami, Norito; Eguchi, Hisashi; Tsutsumi, Akizumi

2016-01-01

Objectives: The present study aimed to examine the buffering effect of workplace social capital (WSC) on the association of job insecurity with psychological distress in Japanese employees. Methods: 2,971 employees from two factories of a manufacturing company in Japan completed a self-administered questionnaire including the scales on job insecurity, WSC, psychological distress, demographic and occupational characteristics, and quantitative workload. Using psychological distress (defined as a total score of the K6 scale ≥5) as a dependent variable, multiple logistic regression analyses were conducted. In a series of analyses, interaction term of job insecurity×WSC was included in the model. Results: After adjusting for demographic and occupational characteristics as well as for quantitative workload and interaction effect of quantitative workload×WSC, high job insecurity and low WSC were significantly associated with psychological distress. Furthermore, a significant interaction effect of job insecurity×WSC was observed. Specifically, the association of job insecurity with psychological distress was greater among those who perceived lower levels of WSC (prevalence odds ratio=3.79 [95% confidence interval=2.70-5.32] for high vs. low job insecurity subgroup) than among those who perceived higher levels of WSC (prevalence odds ratio=2.96 [95% confidence interval=2.19-4.01] for high vs. low job insecurity subgroup). These findings were replicated among permanent male employees in the gender-stratified analyses. Conclusions: The present study suggests that WSC has a buffering effect on the association of job insecurity with psychological distress at least among Japanese permanent male employees. PMID:27488045

Urinary sodium excretion and kidney failure in non-diabetic chronic kidney disease

PubMed Central

Fan, Li; Tighiouart, Hocine; Levey, Andrew S.; Beck, Gerald J.; Sarnak, Mark J.

2014-01-01

Current guidelines recommend under 2g/day sodium intake in chronic kidney disease, but there are few studies relating sodium intake to long-term outcomes. Here we evaluated the association of mean baseline 24-hour urinary sodium excretion with kidney failure and a composite outcome of kidney failure or all-cause mortality using Cox regression in 840 participants enrolled in the Modification of Diet in Renal Disease Study. Mean 24-hour urinary sodium excretion was 3.46 g/day. Kidney failure developed in 617 and the composite outcome was reached in 723. In the primary analyses there was no association between 24-hour urine sodium and kidney failure [HR 0.99 (95% CI 0.91–1.08)] nor on the composite outcome [HR 1.01 (95% CI 0.93–1.09),] each per 1g/day higher urine sodium. In exploratory analyses there was a significant interaction of baseline proteinuria and sodium excretion with kidney failure. Using a 2-slope model, when urine sodium was under 3g/day, higher urine sodium was associated with increased risk of kidney failure in those with baseline proteinuria under 1g/day, and lower risk of kidney failure in those with baseline proteinuria of 1g/day or more. There was no association between urine sodium and kidney failure when urine sodium was 3g/day or more. Results were consistent using first baseline and time-dependent urine sodium. Thus, we noted no association of urine sodium with kidney failure. Results of the exploratory analyses need to be verified in additional studies and the mechanism explored. PMID:24646858

Measuring Future Time Perspective across Adulthood: Development and Evaluation of a Brief Multidimensional Questionnaire

PubMed Central

Brothers, Allyson; Chui, Helena; Diehl, Manfred

2014-01-01

Purpose of the Study: Despite calls for the consideration of future time perspective (FTP) as a multidimensional construct, mostly unidimensional measurement instruments have been used. This study had two objectives: (a) to develop a brief multidimensional questionnaire for assessing FTP in adulthood and evaluate its psychometric properties; and (b) to examine age associations and age-group differences of the dimensions of FTP. Design and Methods: Data were collected from 625 community-residing adults between the ages of 18 and 93, representing young, middle-aged, and older adults. The psychometric evaluation involved exploratory factor analyses (EFA) and confirmatory FA (CFA), reliability and validity analyses, and measurement invariance testing. Zero-order and partial correlations were used to examine the association of the dimensions of FTP with age, and multivariate analysis of variance was used to examine age-group differences. Results: EFA and CFA supported a three-factor solution: Future as Open, Future as Limited, and Future as Ambiguous. Metric measurement invariance for this factor structure was confirmed across the three age groups. Reliability and validity analyses provided evidence of sound psychometric properties of the brief questionnaire. Age was negatively associated with Future as Open and positively associated with Future as Limited. Young adults exhibited significantly greater ambiguity toward the future than middle-aged or older adults. Implications: This study provides evidence in support of the psychometric properties of a new brief multidimensional FTP scale. It also provides evidence for a pattern of age associations and age-group differences consistent with life-span developmental theory. PMID:25063938

FARVATX: FAmily-based Rare Variant Association Test for X-linked genes

PubMed Central

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H.; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-01-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease (COPD). Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. PMID:27325607

FARVATX: Family-Based Rare Variant Association Test for X-Linked Genes.

PubMed

Choi, Sungkyoung; Lee, Sungyoung; Qiao, Dandi; Hardin, Megan; Cho, Michael H; Silverman, Edwin K; Park, Taesung; Won, Sungho

2016-09-01

Although the X chromosome has many genes that are functionally related to human diseases, the complicated biological properties of the X chromosome have prevented efficient genetic association analyses, and only a few significantly associated X-linked variants have been reported for complex traits. For instance, dosage compensation of X-linked genes is often achieved via the inactivation of one allele in each X-linked variant in females; however, some X-linked variants can escape this X chromosome inactivation. Efficient genetic analyses cannot be conducted without prior knowledge about the gene expression process of X-linked variants, and misspecified information can lead to power loss. In this report, we propose new statistical methods for rare X-linked variant genetic association analysis of dichotomous phenotypes with family-based samples. The proposed methods are computationally efficient and can complete X-linked analyses within a few hours. Simulation studies demonstrate the statistical efficiency of the proposed methods, which were then applied to rare-variant association analysis of the X chromosome in chronic obstructive pulmonary disease. Some promising significant X-linked genes were identified, illustrating the practical importance of the proposed methods. © 2016 WILEY PERIODICALS, INC.

Systems biology approach to late-onset Alzheimer's disease genome-wide association study identifies novel candidate genes validated using brain expression data and Caenorhabditis elegans experiments.

PubMed

Mukherjee, Shubhabrata; Russell, Joshua C; Carr, Daniel T; Burgess, Jeremy D; Allen, Mariet; Serie, Daniel J; Boehme, Kevin L; Kauwe, John S K; Naj, Adam C; Fardo, David W; Dickson, Dennis W; Montine, Thomas J; Ertekin-Taner, Nilufer; Kaeberlein, Matt R; Crane, Paul K

2017-10-01

We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci. We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions. We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ toxicity, and NDUFS3, SLC25A11, ATP5H, and APP were differentially expressed in the temporal cortex. Network analyses identified novel LOAD candidate genes. We demonstrated a functional role for four of these in a C. elegans model and found enrichment of differentially expressed genes in the temporal cortex. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Genome-wide association study of carbon and nitrogen metabolism in the maize nested association mapping population

USDA-ARS?s Scientific Manuscript database

Carbon (C) and nitrogen (N) metabolism are critical to plant growth and development and at the basis of yield and adaptation. We have applied high throughput metabolite analyses to over 12,000 diverse field grown samples from the maize nested association mapping population. This allowed us to identi...

Familial covariation of facial emotion recognition and IQ in schizophrenia.

PubMed

Andric, Sanja; Maric, Nadja P; Mihaljevic, Marina; Mirjanic, Tijana; van Os, Jim

2016-12-30

Alterations in general intellectual ability and social cognition in schizophrenia are core features of the disorder, evident at the illness' onset and persistent throughout its course. However, previous studies examining cognitive alterations in siblings discordant for schizophrenia yielded inconsistent results. Present study aimed to investigate the nature of the association between facial emotion recognition and general IQ by applying genetically sensitive cross-trait cross-sibling design. Participants (total n=158; patients, unaffected siblings, controls) were assessed using the Benton Facial Recognition Test, the Degraded Facial Affect Recognition Task (DFAR) and the Wechsler Adult Intelligence Scale-III. Patients had lower IQ and altered facial emotion recognition in comparison to other groups. Healthy siblings and controls did not significantly differ in IQ and DFAR performance, but siblings exhibited intermediate angry facial expression recognition. Cross-trait within-subject analyses showed significant associations between overall DFAR performance and IQ in all participants. Within-trait cross-sibling analyses found significant associations between patients' and siblings' IQ and overall DFAR performance, suggesting their familial clustering. Finally, cross-trait cross-sibling analyses revealed familial covariation of facial emotion recognition and IQ in siblings discordant for schizophrenia, further indicating their familial etiology. Both traits are important phenotypes for genetic studies and potential early clinical markers of schizophrenia-spectrum disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Information needs in people with diabetes mellitus: a systematic review.

PubMed

Biernatzki, Lisa; Kuske, Silke; Genz, Jutta; Ritschel, Michaela; Stephan, Astrid; Bächle, Christina; Droste, Sigrid; Grobosch, Sandra; Ernstmann, Nicole; Chernyak, Nadja; Icks, Andrea

2018-02-14

The purpose of this study was to identify and analyse currently available knowledge on information needs of people with diabetes mellitus, also considering possible differences between subgroups and associated factors. Twelve databases including MEDLINE, EMBASE and the Cochrane Library were searched up until June 2015. Publications that addressed self-reported information needs of people with diabetes mellitus were included. Each study was assessed by using critical appraisal tools, e.g. from the UK National Institute for Health and Care Excellence. Extraction and content analysis were performed systematically. In total, 1993 publications were identified and 26 were finally included. Nine main categories of information needs were identified, including 'treatment-process', 'course of disease', 'abnormalities of glucose metabolism' and 'diabetes through the life cycle'. Differences between patient subgroups, such as type of diabetes or age, were sparsely analysed. Some studies analysed associations between information needs and factors such as participation preferences or information seeking. They found, for example, that information needs on social support or life tasks were associated with information seeking in Internet forums. Information needs in people with diabetes mellitus, appear to be high, yet poorly investigated. Research is needed regarding differences between diverse diabetes populations, including gender aspects or changes in information needs during the disease course. The review protocol has been registered at Prospero ( CRD42015029610 ).

Low Social Status Markers: Do They Predict Depressive Symptoms in Adolescence?

PubMed

Jackson, Benita; Goodman, Elizabeth

2011-07-01

Some markers of social disadvantage are associated robustly with depressive symptoms among adolescents: female gender and lower socioeconomic status (SES), respectively. Others are associated equivocally, notably Black v. White race/ethnicity. Few studies examine whether markers of social disadvantage by gender, SES, and race/ethnicity jointly predict self-reported depressive symptoms during adolescence; this was our goal. Secondary analyses were conducted on data from a socioeconomically diverse community-based cohort study of non-Hispanic Black and White adolescents (N = 1,263, 50.4% female). Multivariable general linear models tested if female gender, Black race/ethnicity, and lower SES (assessed by parent education and household income), and their interactions predicted greater depressive symptoms reported on the Center for Epidemiological Studies-Depression scale. Models adjusted for age and pubertal status. Univariate analyses revealed more depressive symptoms in females, Blacks, and participants with lower SES. Multivariable models showed females across both racial/ethnic groups reported greater depressive symptoms; Blacks demonstrated more depressive symptoms than did Whites but when SES was included this association disappeared. Exploratory analyses suggested Blacks gained less mental health benefit from increased SES. However there were no statistically significant interactions among gender, race/ethnicity, or SES. Taken together, we conclude that complex patterning among low social status domains within gender, race/ethnicity, and SES predicts depressive symptoms among adolescents.

Using the gene ontology to scan multilevel gene sets for associations in genome wide association studies.

PubMed

Schaid, Daniel J; Sinnwell, Jason P; Jenkins, Gregory D; McDonnell, Shannon K; Ingle, James N; Kubo, Michiaki; Goss, Paul E; Costantino, Joseph P; Wickerham, D Lawrence; Weinshilboum, Richard M

2012-01-01

Gene-set analyses have been widely used in gene expression studies, and some of the developed methods have been extended to genome wide association studies (GWAS). Yet, complications due to linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs), and variable numbers of SNPs per gene and genes per gene-set, have plagued current approaches, often leading to ad hoc "fixes." To overcome some of the current limitations, we developed a general approach to scan GWAS SNP data for both gene-level and gene-set analyses, building on score statistics for generalized linear models, and taking advantage of the directed acyclic graph structure of the gene ontology when creating gene-sets. However, other types of gene-set structures can be used, such as the popular Kyoto Encyclopedia of Genes and Genomes (KEGG). Our approach combines SNPs into genes, and genes into gene-sets, but assures that positive and negative effects of genes on a trait do not cancel. To control for multiple testing of many gene-sets, we use an efficient computational strategy that accounts for LD and provides accurate step-down adjusted P-values for each gene-set. Application of our methods to two different GWAS provide guidance on the potential strengths and weaknesses of our proposed gene-set analyses. © 2011 Wiley Periodicals, Inc.

Lack of association between the P413L variant of chromogranin B and ALS risk or age at onset: a meta-analysis.

PubMed

Yang, Xinglong; Li, Shimei; Xing, Dongmei; Li, Peiyun; Li, Ci; Qi, Ling; Xu, Yanming; Ren, Hui

2018-02-01

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is thought to result from interaction of genetic and environmental risk factors. Whether the potentially functional exonic P413L variant in the chromogranin B gene influences ALS risk and age at onset is controversial. We meta-analysed or other studies assessing the association between the P413L variant and ALS risk or age at ALS onset indexed in Web of Science, PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases. Five case-control studies were analysed, involving 2639 patients with sporadic ALS, 201 with familial ALS and 3381 controls. No association was detected between risk of either ALS type and the CT + TT genotype or T-allele of the P413L variant. Age at ALS onset was similar between carriers and non-carriers of the T-allele. The available evidence suggests that the P413L variant of chromogranin B is not associated with ALS risk or age at ALS onset. These results should be validated in large, well-designed studies.

Evaluating the Association of Workplace Psychosocial Stressors with Occupational Injury, Illness, and Assault

PubMed Central

Brown, Lezah P.; Rospenda, Kathleen M.; Sokas, Rosemary K.; Conroy, Lorraine; Freels, Sally; Swanson, Naomi G.

2014-01-01

Objective This research project characterizes occupational injuries, illnesses, and assaults (OIIAs) as a negative outcome associated with worker exposure to generalized workplace abuse/harassment, sexual harassment, and job threat and pressure. Methods Data were collected in a nationwide random-digit-dial telephone survey conducted during 2003–2004. There were 2,151 study interviews conducted in English and Spanish. Analyses included cross tabulation with Pearson’s Chi-Square, and logistic regression analyses. Results Three hundred fifty-one (351) study participants reported having an OIIA during the 12 months preceding the study. Occurrences of generalized workplace harassment (O.R.= 1.53; CI = 1.33 – 1.75, p≤ 0.05), sexual harassment (O.R.= 1. 18; CI = 1.04 –1.34, p≤ 0.05), and job pressure and threat (O.R.=1.26; CI = 1.10–1.45, p≤ 0.05), were significantly associated with reporting an OIIA. Conclusions The psychosocial environment is significantly associated with an increased risk of OIIA. Further research is needed to understand causal pathways and to explore potential interventions. PMID:21154106

Triglyceride and glucose (TyG) index as a predictor of incident hypertension: a 9-year longitudinal population-based study.

PubMed

Zheng, Rongjiong; Mao, Yushan

2017-09-13

Hypertension and the triglyceride and glucose index both have been associated with insulin resistance; however, the longitudinal association remains unclear. This study was designed to investigate the longitudinal association between the triglyceride and glucose index and incident hypertension among the Chinese population. We studied 4686 subjects (3177 males and 1509 females) and followed up for 9 years. The subjects were divided into four groups based on the triglyceride and glucose index. Univariate and multivariate Cox regression models were used to analyse the risk factors of hypertension. After 9 years of follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative incidence of hypertension was 43.7%, ranging from 28.5% in quartile 1 to 36.9% in quartile 2, 49.2% in quartile 3 and 59.8% in quartile 4 (p for trend < 0.001). Cox regression analyses indicated that higher triglyceride and glucose index was associated with an increased risk of subsequent incident hypertension. The triglyceride and glucose index can predict the incident hypertension among the Chinese population.

Source-specific workplace social support and high-sensitivity C-reactive protein levels among Japanese workers: A 1-year prospective cohort study.

PubMed

Eguchi, Hisashi; Shimazu, Akihito; Kawakami, Norito; Inoue, Akiomi; Tsutsumi, Akizumi

2016-08-01

This study investigated the prospective association between source-specific workplace social support and high-sensitivity C-reactive protein (hs-CRP) levels in workers in Japan. We conducted a 1-year prospective cohort study with 1,487 men and 533 women aged 18-65 years. Participants worked at two manufacturing worksites in Japan and were free of major illness. We used multivariable linear regression analyses to evaluate the prospective association between supervisor and coworker support at baseline, and hs-CRP levels at follow-up. We conducted the analyses separately for men and women. For women, high supervisor support at baseline was significantly associated with lower hs-CRP levels at follow-up (β = -0.109, P < 0.01), whereas coworker support at baseline was not significantly associated with hs-CRP levels at follow-up. Associations between supervisor and coworker support and hs-CRP levels were not significant for men. Supervisor support may have beneficial effects on inflammatory markers in working women. Am. J. Ind. Med. 59:676-684, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

PLASMA DIHYDROCERAMIDE SPECIES ASSOCIATE WITH WAIST CIRCUMFERENCE IN MEXICAN AMERICAN FAMILIES

PubMed Central

Mamtani, Manju; Meikle, Peter J.; Kulkarni, Hemant; Weir, Jacquelyn M.; Barlow, Christopher K.; Jowett, Jeremy B.; Bellis, Claire; Dyer, Thomas D.; Almasy, Laura; Mahaney, Michael C.; Duggirala, Ravindranath; Comuzzie, Anthony G.; Blangero, John; Curran, Joanne E.

2013-01-01

Objective Waist circumference (WC), the clinical marker of central obesity, is gaining popularity as a screening tool for type 2 diabetes (T2D). While there is epidemiologic evidence favoring the WC-T2D association, its biological substantiation is generally weak. Our objective was to determine the independent association of plasma lipid repertoire with WC. Design and methods We used samples and data from the San Antonio Family Heart Study of 1208 Mexican Americans from 42 extended families. We determined association of plasma lipidomic profiles with the cross-sectionally assessed WC. Plasma lipidomic profiling entailed liquid chromatography with mass spectrometry. Statistical analyses included multivariable polygenic regression models and bivariate trait analyses using the SOLAR software. Results After adjusting for age and sex interactions, body mass index, homeostasis model of assessment – insulin resistance, total cholesterol, triglycerides, high density lipoproteins and use of lipid lowering drugs, dihydroceramides as a class were associated with WC. Dihydroceramide species 18:0, 20:0, 22:0 and 24:1 were significantly associated and genetically correlated with WC. Two sphingomyelin species (31:1 and 41:1) were also associated with WC. Conclusions Plasma dihydroceramide levels independently associate with WC. Thus, high resolution plasma lipidomic studies can provide further credence to the biological underpinnings of the association of WC with T2D. PMID:23929697

Parenting Characteristics Associated with Anxiety and Depression: A Multivariate Approach

ERIC Educational Resources Information Center

Anhalt, Karla; Morris, Tracy L.

2008-01-01

This study examined the association between perceived parenting factors and symptoms of social anxiety, generalized anxiety and depression. Participants rated experiences with their mothers and fathers with regard to parental care, overprotection, criticism, parent-adolescent attachment, and family sociability. Regression analyses examined the…

TSLP Polymorphisms are Associated with Asthma in a Sex-Specific Fashion

PubMed Central

Hunninghake, Gary M.; Soto-Quirós, Manuel E.; Avila, Lydiana; Kim, Hong P.; Lasky-Su, Jessica; Rafaels, Nicholas; Ruczinski, Ingo; Beaty, Terry H.; Mathias, Rasika A.; Barnes, Kathleen C.; Wilk, Jemma B.; O’Connor, George T.; Gauderman, W. James; Vora, Hita; Baurley, James W.; Gilliland, Frank; Liang, Catherine; Sylvia, Jody S.; Klanderman, Barbara J.; Sharma, Sunita S.; Himes, Blanca E.; Bossley, Cara J.; Israel, Elliot; Raby, Benjamin A.; Bush, Andrew; Choi, Augustine M.; Weiss, Scott T.; Celedón, Juan C.

2010-01-01

Background Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. Methods We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of asthmatic children in Costa Rica. Significant findings were replicated in white and African-American participants in the Childhood Asthma Management Program, in African Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children’s Health Study, and in whites in the Framingham Heart Study (FHS). Main Results Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (p values of 2×10−5 and 1×10−5, respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (p= 3×10−6). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (p= 2×10−4). Findings for rs2289276 were consistent in all cohorts except the FHS. Conclusions TSLP variants are associated with asthma in a sex-specific fashion. PMID:20560908

TSLP polymorphisms are associated with asthma in a sex-specific fashion.

PubMed

Hunninghake, G M; Soto-Quirós, M E; Avila, L; Kim, H P; Lasky-Su, J; Rafaels, N; Ruczinski, I; Beaty, T H; Mathias, R A; Barnes, K C; Wilk, J B; O'Connor, G T; Gauderman, W James; Vora, H; Baurley, J W; Gilliland, F; Liang, C; Sylvia, J S; Klanderman, B J; Sharma, S S; Himes, B E; Bossley, C J; Israel, E; Raby, B A; Bush, A; Choi, A M; Weiss, S T; Celedón, J C

2010-12-01

Single nucleotide polymorphisms (SNPs) in thymic stromal lymphopoietin (TSLP) have been associated with IgE (in girls) and asthma (in general). We sought to determine whether TSLP SNPs are associated with asthma in a sex-specific fashion. We conducted regular and sex-stratified analyses of association between SNPs in TSLP and asthma in families of children with asthma in Costa Rica. Significant findings were replicated in whites and African-American participants in the Childhood Asthma Management Program, in African-Americans in the Genomic Research on Asthma in the African Diaspora study, in whites and Hispanics in the Children's Health Study, and in whites in the Framingham Heart Study (FHS). Two SNPs in TSLP (rs1837253 and rs2289276) were significantly associated with a reduced risk of asthma in combined analyses of all cohorts (P values of 2 × 10(-5) and 1 × 10(-5) , respectively). In a sex-stratified analysis, the T allele of rs1837253 was significantly associated with a reduced risk of asthma in males only (P = 3 × 10(-6) ). Alternately, the T allele of rs2289276 was significantly associated with a reduced risk of asthma in females only (P = 2 × 10(-4) ). Findings for rs2289276 were consistent in all cohorts except the FHS. TSLP variants are associated with asthma in a sex-specific fashion. © 2010 John Wiley & Sons A/S.

Participation in organized sports is positively associated with employment in adults with spinal cord injury.

PubMed

Blauwet, Cheri; Sudhakar, Supreetha; Doherty, Ashley L; Garshick, Eric; Zafonte, Ross; Morse, Leslie R

2013-05-01

The aim of this study was to determine the association between participation in organized sports programs and employment in adults with chronic spinal cord injury. This is a cross-sectional study of 149 adults with chronic spinal cord injury. Motor level and completeness of injury were confirmed by physical examination. Information related to demographics, employment, level of education, body mass index, duration of injury, participation in individually planned exercise, and participation in organized sports was obtained using a standardized questionnaire. Multivariable logistic regression analyses were used to assess factors associated with employment. In univariate analyses, employment was associated with younger age (P = 0.001) and a higher level of education (P = 0.01), whereas obesity decreased the likelihood of employment (P = 0.04). Participation in organized sports approached significance (P = 0.06). In the multivariable analysis and after adjusting for age, education, and body mass index, participation in organized sports was significantly associated with employment (odds ratio, 2.4; P = 0.04). Sex, duration of injury, wheelchair use, and participation in individually planned exercise were not significantly associated with employment (P = 0.16-0.94). In the adults with chronic spinal cord injury, participation in organized sports was positively associated with employment. Further studies are necessary to determine the causative nature of this association and how various factors related to sports participation may contribute.

Women Firefighters and Workplace Harassment: Associated Suicidality and Mental Health Sequelae.

PubMed

Hom, Melanie A; Stanley, Ian H; Spencer-Thomas, Sally; Joiner, Thomas E

2017-12-01

This cross-sectional study investigated the association between harassment, career suicidality, and psychiatric symptoms among women firefighters. Women firefighters (n = 290) completed self-report measures of experiences with harassment on the job, career suicidality, and various psychiatric symptoms. Logistic regression analyses and one-way analyses of variance were used to address study aims. Of the sample, 21.7% reported having experienced sexual harassment and 20.3% reported having been threatened or harassed in another way on their firefighting job. Sexual harassment and other threats/harassment on the job were both significantly associated with a greater likelihood of reporting career suicidal ideation, as well as reporting more severe psychiatric symptoms. Harassment and threats experienced on the job may be associated with increased suicide risk and more severe psychiatric symptoms among women firefighters. Efforts are needed to reduce the occurrence of harassment and threats within the fire service and provide support for women firefighters who have been harassed or threatened.

Consensually defined facets of personality as prospective predictors of change in depression symptoms.

PubMed

Naragon-Gainey, Kristin; Watson, David

2014-08-01

Depression has robust associations with personality, showing a strong relation with neuroticism and more moderate associations with extraversion and conscientiousness. In addition, each Big Five domain can be decomposed into narrower facets. However, we currently lack consensus as to the contents of Big Five facets, with idiosyncrasies across instruments; moreover, few studies have examined associations with depression. In the current study, community participants completed six omnibus personality inventories; self-reported depressive symptoms were assessed at baseline and 5 years later. Exploratory factor analyses suggested three to five facets in each domain, and these facets served as prospective predictors of depression in hierarchical regressions, after accounting for baseline and trait depression. In these analyses, high anger (from neuroticism), low positive emotionality (extraversion), low conventionality (conscientiousness), and low culture (openness to experiences) were significant prospective predictors of depression. Results are discussed in regard to personality structure and assessment, as well as personality-psychopathology associations. © The Author(s) 2014.

Smoking among young urban Malaysian women and its risk factors.

PubMed

Manaf, Rosliza A; Shamsuddin, Khadijah

2008-01-01

This study was conducted to measure the prevalence of cigarette smoking and to determine the individual, family, and environmental factors associated with smoking among young urban women. A cross-sectional study through self-administered questionnaire was conducted on female students enrolled in private higher learning institutions in Kuala Lumpur and Selangor, Malaysia, between July and October 2005. Analysis on 408 respondents showed that current smoker prevalence rate was 18.6%. Adjusted analyses showed significant association between smoking and individual factors, which are the importance of slim image, average monthly allowance, and car ownership. For family factors, analyses showed significant association between smoking and parental marital status and smoking status of male siblings. Strong associations were seen between female smoking and environmental factors, such as having more smoker friends, having smokers as best friends, keeping cigarette-brand items, being offered free cigarette, and perceiving female smoking as normal. The identified risk factors could be used to develop more effective prevention programs to overcome smoking among young urban women.

Heritability and molecular-genetic basis of the P3 event-related brain potential: A genome-wide association study

PubMed Central

MALONE, STEPHEN M.; VAIDYANATHAN, UMA; BASU, SAONLI; MILLER, MICHAEL B.; MCGUE, MATT; IACONO, WILLIAM G.

2014-01-01

P3 amplitude is a candidate endophenotype for disinhibitory psychopathology, psychosis, and other disorders. The present study is a comprehensive analysis of the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic factor score in a large community sample (N = 4,211) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric models indicated that as much as 65% of the variance in each measure was due to additive genes. All SNPs in aggregate accounted for approximately 40% to 50% of the heritable variance. However, analyses of individual SNPs did not yield any significant associations. Analyses of individual genes did not confirm previous associations between P3 amplitude and candidate genes but did yield a novel association with myelin expression factor 2 (MYEF2). Main effects of individual variants may be too small to be detected by GWAS without larger samples. PMID:25387705

Using a health message with a testimonial to motivate colon cancer screening: associations with perceived identification and vividness.

PubMed

Dillard, Amanda J; Main, Jackie L

2013-12-01

Research suggests that testimonials, or first-person narratives, influence health behavior and health-related decision making, but few studies have examined conceptual factors that may be responsible for these effects. In the current study, older adults who were due for colorectal cancer screening read a message about screening that included a testimonial from a similar other who had previously made the screening decision. We assessed participants' identification with the testimonial character and the degree to which they found the message to be vivid. We explored associations between these factors and participants' knowledge following the message, mood, certainty about screening, and their behavioral intentions to look for more information about screening and to have a test in the next year. In bivariate analyses, identification and vividness were both significantly, positively associated with knowledge and behavioral intentions to have screening in the next year. However, multivariate analyses revealed that only vividness remained significantly associated with knowledge and intentions to be screened.

Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion.

PubMed

Pereza, Nina; Ostojić, Saša; Kapović, Miljenko; Peterlin, Borut

2017-01-01

1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA. Systematic review and meta-analysis. Not applicable. Couples with IRSA and their spontaneously aborted embryos. Summary odds ratios (ORs) were calculated by means of fixed- or random-effects models. Association of genetic variants with IRSA. The systematic review included 428 case-control studies (1990-2015), which differed substantially regarding RSA definition, clinical evaluation of patients, and selection of control subjects. In women, 472 variants in 187 genes were investigated. Meta-analyses were performed for 36 variants in 16 genes. Association with IRSA defined as three or more spontaneous abortions (SAs) was detected for 21 variants in genes involved in immune response (IFNG, IL10, KIR2DS2, KIR2DS3, KIR2DS4, MBL, TNF), coagulation (F2, F5, PAI-1, PROZ), metabolism (GSTT1, MTHFR), and angiogenesis (NOS3, VEGFA). However, ORs were modest (0.51-2.37), with moderate or weak epidemiologic credibility. Minor differences in summary ORs were detected between IRSA defined as two or more and as three or more SAs. Male partners were included in 12.1% of studies, and one study included spontaneously aborted embryos. Candidate gene studies show moderate associations with IRSA. Owing to large differences in RSA definition and selection criteria for participants, consensus is needed. Future GASs should include both partners and spontaneously aborted embryos. Genome-wide association studies and large-scale replications of identified associations are recommended. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Sedentary behaviours and its association with bone mass in adolescents: the HELENA cross-sectional study

PubMed Central

2012-01-01

Background We aimed to examine whether time spent on different sedentary behaviours is associated with bone mineral content (BMC) in adolescents, after controlling for relevant confounders such as lean mass and objectively measured physical activity (PA), and if so, whether extra-curricular participation in osteogenic sports could have a role in this association. Methods Participants were 359 Spanish adolescents (12.5-17.5 yr, 178 boys,) from the HELENA-CSS (2006–07). Relationships of sedentary behaviours with bone variables were analysed by linear regression. The prevalence of low BMC (at least 1SD below the mean) and time spent on sedentary behaviours according to extracurricular sport participation was analysed by Chi-square tests. Results In boys, the use of internet for non-study was negatively associated with whole body BMC after adjustment for lean mass and moderate to vigorous PA (MVPA). In girls, the time spent studying was negatively associated with femoral neck BMC. Additional adjustment for lean mass slightly reduced the negative association between time spent studying and femoral neck BMC. The additional adjustment for MVPA did not change the results at this site. The percentage of girls having low femoral neck BMC was significantly smaller in those participating in osteogenic sports (≥ 3 h/week) than in the rest, independently of the cut-off selected for the time spent studying. Conclusions The use of internet for non-study (in boys) and the time spent studying (in girls) are negatively associated with whole body and femoral neck BMC, respectively. In addition, at least 3 h/week of extra-curricular osteogenic sports may help to counteract the negative association of time spent studying on bone health in girls. PMID:23148760

Examining the associations between HIV-related stigma and health outcomes in people living with HIV/AIDS: a series of meta-analyses.

PubMed

Rueda, Sergio; Mitra, Sanjana; Chen, Shiyi; Gogolishvili, David; Globerman, Jason; Chambers, Lori; Wilson, Mike; Logie, Carmen H; Shi, Qiyun; Morassaei, Sara; Rourke, Sean B

2016-07-13

To conduct a systematic review and series of meta-analyses on the association between HIV-related stigma and health among people living with HIV. A structured search was conducted on 6 electronic databases for journal articles reporting associations between HIV-related stigma and health-related outcomes published between 1996 and 2013. Controlled studies, cohort studies, case-control studies and cross-sectional studies in people living with HIV were considered for inclusion. Mental health (depressive symptoms, emotional and mental distress, anxiety), quality of life, physical health, social support, adherence to antiretroviral therapy, access to and usage of health/social services and risk behaviours. 64 studies were included in our meta-analyses. We found significant associations between HIV-related stigma and higher rates of depression, lower social support and lower levels of adherence to antiretroviral medications and access to and usage of health and social services. Weaker relationships were observed between HIV-related stigma and anxiety, quality of life, physical health, emotional and mental distress and sexual risk practices. While risk of bias assessments revealed overall good quality related to how HIV stigma and health outcomes were measured on the included studies, high risk of bias among individual studies was observed in terms of appropriate control for potential confounders. Additional research should focus on elucidating the mechanisms behind the negative relationship between stigma and health to better inform interventions to reduce the impact of stigma on the health and well-being of people with HIV. This systematic review and series of meta-analyses support the notion that HIV-related stigma has a detrimental impact on a variety of health-related outcomes in people with HIV. This review can inform the development of multifaceted, intersectoral interventions to reduce the impact of HIV-related stigma on the health and well-being of people living with HIV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Temporal changes in occupational sitting time in the Danish workforce and associations with all-cause mortality: results from the Danish work environment cohort study.

PubMed

van der Ploeg, Hidde P; Møller, Simone Visbjerg; Hannerz, Harald; van der Beek, Allard J; Holtermann, Andreas

2015-06-02

Prolonged sitting has been negatively associated with a range of non-communicably diseases. However, the role of occupational sitting is less clear, and little is known on the changes of occupational sitting in a working population over time. The present study aimed to determine 1) temporal changes in occupational sitting time between 1990 and 2010 in the Danish workforce; 2) the association and possible dose-response relationship between occupational sitting time and all-cause mortality. This study analysed data from the Danish Work Environment Cohort Study (DWECS), which is a cohort study of the Danish working population conducted in five yearly intervals between 1990 and 2010. Occupational sitting time is self-reported in the DWECS. To determine the association with all-cause mortality, the DWECS was linked to the Danish Register of Causes of Death via the Central Person Register. Between 1990 and 2010 the proportion of the Danish workforce who sat for at least three quarters of their work time gradually increased from 33.1 to 39.1%. All-cause mortality analyses were performed with 149,773 person-years of observation and an average follow-up of 12.61 years, during which 533 deaths were registered. None of the presented analyses found a statistically significant association between occupational sitting time and all-cause mortality. The hazard ratio for all-cause mortality was 0.97 (95% CI: 0.79; 1.18) when ≥24 hr/wk occupational sitting time was compared to <24 hr/wk for the 1990-2005 waves. Occupational sitting time increased by 18% in the Danish workforce, which seemed to be limited to people with high socio-economic status. If this increase is accompanied by increases in total sitting time, this development has serious public health implications, given the detrimental associations between total sitting time and mortality. The current study was inconclusive on the specific role that occupational sitting might play in the increased all-cause mortality risk associated with the total volume of sitting.

Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis.

PubMed

Grosso, Giuseppe; Micek, Agnieszka; Godos, Justyna; Sciacca, Salvatore; Pajak, Andrzej; Martínez-González, Miguel A; Giovannucci, Edward L; Galvano, Fabio

2016-12-01

Coffee consumption has been associated with several benefits toward human health. However, its association with mortality risk has yielded contrasting results, including a non-linear relation to all-cause and cardiovascular disease (CVD) mortality and no association with cancer mortality. As smoking habits may affect the association between coffee and health outcomes, the aim of the present study was to update the latest dose-response meta-analysis of prospective cohort studies on the association between coffee consumption and mortality risk and conduct stratified analyses by smoking status and other potential confounders. A systematic search was conducted in electronic databases to identify relevant studies, risk estimates were retrieved from the studies, and dose-response analysis was modeled by using restricted cubic splines. A total of 31 studies comprising 1610,543 individuals and 183,991 cases of all-cause, 34,574 of CVD, and 40,991 of cancer deaths were selected. Analysis showed decreased all-cause [relative risk (RR) = 0.86, 95 % confidence interval (CI) = 0.82, 0.89)] and CVD mortality risk (RR = 0.85, 95 % CI = 0.77, 0.93) for consumption of up to 4 cups/day of coffee, while higher intakes were associated with no further lower risk. When analyses were restricted only to non-smokers, a linear decreased risk of all-cause (RR = 0.94, 95 % CI = 0.93, 0.96), CVD (RR = 0.94, 95 % CI = 0.91, 0.97), and cancer mortality (RR = 0.98, 95 % CI = 0.96, 1.00) for 1 cup/day increase was found. The search for other potential confounders, including dose-response analyses in subgroups by gender, geographical area, year of publication, and type of coffee, showed no relevant differences between strata. In conclusion, coffee consumption is associated with decreased risk of mortality from all-cause, CVD, and cancer; however, smoking modifies the observed risk when studying the role of coffee on human health.

Meta-analytic evaluation of the association between head injury and risk of amyotrophic lateral sclerosis.

PubMed

Watanabe, Yukari; Watanabe, Takamitsu

2017-10-01

Head injury is considered as a potential risk factor for amyotrophic lateral sclerosis (ALS). However, several recent studies have suggested that head injury is not a cause, but a consequence of latent ALS. We aimed to evaluate such a possibility of reverse causation with meta-analyses considering time lags between the incidence of head injuries and the occurrence of ALS. We searched Medline and Web of Science for case-control, cross-sectional, or cohort studies that quantitatively investigated the head-injury-related risk of ALS and were published until 1 December 2016. After selecting appropriate publications based on PRISMA statement, we performed random-effects meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CI). Sixteen of 825 studies fulfilled the eligibility criteria. The association between head injuries and ALS was statistically significant when the meta-analysis included all the 16 studies (OR 1.45, 95% CI 1.21-1.74). However, in the meta-analyses considering the time lags between the experience of head injuries and diagnosis of ALS, the association was weaker (OR 1.21, 95% CI 1.01-1.46, time lag ≥ 1 year) or not significant (e.g. OR 1.16, 95% CI 0.84-1.59, time lag ≥ 3 years). Although it did not deny associations between head injuries and ALS, the current study suggests a possibility that such a head-injury-oriented risk of ALS has been somewhat overestimated. For more accurate evaluation, it would be necessary to conduct more epidemiological studies that consider the time lags between the occurrence of head injuries and the diagnosis of ALS.

Replication Study Confirms the Association of the Common rs1800629 Variant of the TNFα Gene with Postmenopausal Osteoporosis Susceptibility in the Han Chinese Population.

PubMed

Jin, Xiaona; Zhou, Baozhen; Zhang, Dangfeng

2018-04-01

Previous studies have suggested that tumor necrosis factor α (TNF-α), encoded by the TNFα gene, can increase osteoclast formation, and that specific alleles of the TNFα gene are associated with postmenopausal osteoporosis susceptibility in some populations; however, the exact molecular mechanism remains unknown. To investigate the potential association of nineteen polymorphisms of the TNFα gene with postmenopausal osteoporosis and bone mineral density (BMD) traits in a sample of 1288 postmenopausal women from the Han Chinese population. A total of 437 postmenopausal osteoporosis patients and 851 unrelated age-matched healthy women were recruited to the study. Single marker and haplotype based analyses were conducted to evaluate the association of nineteen single nucleotide polymorphisms (SNPs) in both patient and control groups. The SNP rs1800629 was identified as being highly significantly associated with postmenopausal osteoporosis after accounting for age and body mass index (p = 0.000087). In addition, the GG genotype of this SNP was associated with significantly lower measures of femoral neck BMD and lumbar spine BMD. Moreover, haplotype based analyses suggested significant association signals between the haplotype block, including rs1800629 with postmenopausal osteoporosis (p < 0.001). We have shown that a TNFα gene polymorphism, rs1800629, is highly significantly associated with postmenopausal osteoporosis and BMD in the female Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this genomic region and its relationship with osteoporosis-related phenotypes.

Genetic polymorphisms in ESR1 and ESR2 genes, and risk of hypospadias in a multiethnic study population.

PubMed

Choudhry, Shweta; Baskin, Laurence S; Lammer, Edward J; Witte, John S; Dasgupta, Sudeshna; Ma, Chen; Surampalli, Abhilasha; Shen, Joel; Shaw, Gary M; Carmichael, Suzan L

2015-05-01

Estrogenic endocrine disruptors acting via estrogen receptors α (ESR1) and β (ESR2) have been implicated in the etiology of hypospadias, a common congenital malformation of the male external genitalia. We determined the association of single nucleotide polymorphisms in ESR1 and ESR2 genes with hypospadias in a racially/ethnically diverse study population of California births. We investigated the relationship between hypospadias and 108 ESR1 and 36 ESR2 single nucleotide polymorphisms in 647 cases and 877 population based nonmalformed controls among infants born in selected California counties from 1990 to 2003. Subgroup analyses were performed by race/ethnicity (nonHispanic white and Hispanic subjects) and by hypospadias severity (mild to moderate and severe). Odds ratios for 33 of the 108 ESR1 single nucleotide polymorphisms had p values less than 0.05 (p = 0.05 to 0.007) for risk of hypospadias. However, none of the 36 ESR2 single nucleotide polymorphisms was significantly associated. In stratified analyses the association results were consistent by disease severity but different sets of single nucleotide polymorphisms were significantly associated with hypospadias in nonHispanic white and Hispanic subjects. Due to high linkage disequilibrium across the single nucleotide polymorphisms, haplotype analyses were conducted and identified 6 haplotype blocks in ESR1 gene that had haplotypes significantly associated with an increased risk of hypospadias (OR 1.3 to 1.8, p = 0.04 to 0.00001). Similar to single nucleotide polymorphism analysis, different ESR1 haplotypes were associated with risk of hypospadias in nonHispanic white and Hispanic subjects. No significant haplotype association was observed for ESR2. The data provide evidence that ESR1 single nucleotide polymorphisms and haplotypes influence the risk of hypospadias in white and Hispanic subjects, and warrant further examination in other study populations. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption

PubMed Central

Bergen, Andrew W.; Michel, Martha; Nishita, Denise; Krasnow, Ruth; Javitz, Harold S.; Conneely, Karen N.; Lessov-Schlaggar, Christina N.; Hops, Hyman; Zhu, Andy Z. X.; Baurley, James W.; McClure, Jennifer B.; Hall, Sharon M.; Baker, Timothy B.; Conti, David V.; Benowitz, Neal L.; Lerman, Caryn; Tyndale, Rachel F.; Swan, Gary E.

2015-01-01

The Nicotine Metabolite Ratio (NMR, ratio of trans-3’-hydroxycotinine and cotinine), has previously been associated with CYP2A6 activity, response to smoking cessation treatments, and cigarette consumption. We searched for drug metabolizing enzyme and transporter (DMET) gene variation associated with the NMR and prospective abstinence in 2,946 participants of laboratory studies of nicotine metabolism and of clinical trials of smoking cessation therapies. Stage I was a meta-analysis of the association of 507 common single nucleotide polymorphisms (SNPs) at 173 DMET genes with the NMR in 449 participants of two laboratory studies. Nominally significant associations were identified in ten genes after adjustment for intragenic SNPs; CYP2A6 and two CYP2A6 SNPs attained experiment-wide significance adjusted for correlated SNPs (CYP2A6 P ACT=4.1E-7, rs4803381 P ACT=4.5E-5, rs1137115, P ACT=1.2E-3). Stage II was mega-regression analyses of 10 DMET SNPs with pretreatment NMR and prospective abstinence in up to 2,497 participants from eight trials. rs4803381 and rs1137115 SNPs were associated with pretreatment NMR at genome-wide significance. In post-hoc analyses of CYP2A6 SNPs, we observed nominally significant association with: abstinence in one pharmacotherapy arm; cigarette consumption among all trial participants; and lung cancer in four case:control studies. CYP2A6 minor alleles were associated with reduced NMR, CPD, and lung cancer risk. We confirmed the major role that CYP2A6 plays in nicotine metabolism, and made novel findings with respect to genome-wide significance and associations with CPD, abstinence and lung cancer risk. Additional multivariate analyses with patient variables and genetic modeling will improve prediction of nicotine metabolism, disease risk and smoking cessation treatment prognosis. PMID:26132489

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

PubMed

Arthur, Anna E; Goss, Amy M; Demark-Wahnefried, Wendy; Mondul, Alison M; Fontaine, Kevin R; Chen, Yi Tang; Carroll, William R; Spencer, Sharon A; Rogers, Laura Q; Rozek, Laura S; Wolf, Gregory T; Gower, Barbara A

2018-03-31

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted. © 2018 UICC.

Segregation of anterior temporal regions critical for retrieving names of unique and non-unique entities reflects underlying long-range connectivity.

PubMed

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2016-02-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category-specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus (UNC) was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus (ILF) was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2008-04-09

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

A Combined Pathway and Regional Heritability Analysis Indicates NETRIN1 Pathway Is Associated With Major Depressive Disorder.

PubMed

Zeng, Yanni; Navarro, Pau; Fernandez-Pujals, Ana M; Hall, Lynsey S; Clarke, Toni-Kim; Thomson, Pippa A; Smith, Blair H; Hocking, Lynne J; Padmanabhan, Sandosh; Hayward, Caroline; MacIntyre, Donald J; Wray, Naomi R; Deary, Ian J; Porteous, David J; Haley, Chris S; McIntosh, Andrew M

2017-02-15

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk. We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and linear mixed model analyses, was tested. In GS:SFHS, four pathways were significantly associated with MDD, and two of these explained a significant amount of pathway-level regional heritability. In PGC:MDD, one pathway was significantly associated with MDD. Pathway-level regional heritability was significant in this pathway in one subset of PGC:MDD. For both samples the regional heritabilities were further localized to the gene and subregion levels. The NETRIN1 signaling pathway showed the most consistent association with MDD across the two samples. PRSs from this pathway showed competitive predictive accuracy compared with the whole-genome PRSs when using area under the curve statistics, logistic regression, and linear mixed model. These post-GWAS analyses highlight the value of combining multiple methods on multiple GWAS data for the identification of risk pathways for MDD. The NETRIN1 signaling pathway is identified as a candidate pathway for MDD and should be explored in further large population studies. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

No association between gender inequality and peak HIV prevalence in developing countries - an ecological study.

PubMed

Kenyon, Chris R; Buyze, Jozefien

2015-01-01

The prevalence of both gender inequality and HIV prevalence vary considerably both within all developing countries and within those in sub-Saharan Africa. We test the hypothesis that the extent of gender inequality is associated with national peak HIV prevalence. Linear regression was used to test the association between national peak HIV prevalence and three markers of gender equality - the gender-related development index (GDI), the gender empowerment measure (GEM), and the gender inequality index (GII). No evidence was found of a positive relationship between gender inequality and HIV prevalence, either in the analyses of all developing countries or those limited to Africa. In the bivariate analyses limited to Africa, there was a positive association between the two measures of gender "equality" and peak HIV prevalence (GDI: coefficient 28, 95% confidence interval (CI) 9.1-46.8; GEM: coefficient 54.8, 95% CI 20.5-89.1). There was also a negative association between the marker of gender "inequality" and peak HIV prevalence (GII: coefficient -66.9, 95% CI -112.8 to -21.0). These associations all disappeared on multivariate analyses. We could not find any evidence to support the hypothesis that variations in the extent of gender inequality explain variations in HIV prevalence in developing countries.

Individual, Psychosocial, and Social Correlates of Unprotected Anal Intercourse in a New Generation of Young Men Who Have Sex With Men in New York City

PubMed Central

Kapadia, Farzana; Siconolfi, Daniel E.; Moeller, Robert W.; Figueroa, Rafael Perez; Barton, Staci C.; Blachman-Forshay, Jaclyn

2013-01-01

Objectives. We examined associations of individual, psychosocial, and social factors with unprotected anal intercourse (UAI) among young men who have sex with men in New York City. Methods. Using baseline assessment data from 592 young men who have sex with men participating in an ongoing prospective cohort study, we conducted multivariable logistic regression analyses to examine the associations between covariates and likelihood of recently engaging in UAI with same-sex partners. Results. Nineteen percent reported recent UAI with a same-sex partner. In multivariable models, being in a current relationship with another man (adjusted odds ratio [AOR] = 4.87), an arrest history (AOR = 2.01), greater residential instability (AOR = 1.75), and unstable housing or homelessness (AOR = 3.10) was associated with recent UAI. Although high levels of gay community affinity and low internalized homophobia were associated with engaging in UAI in bivariate analyses, these associations did not persist in multivariable analyses. Conclusions. Associations of psychosocial and socially produced conditions with UAI among a new generation of young men who have sex with men warrant that HIV prevention programs and policies address structural factors that predispose sexual risk behaviors. PMID:23488487

Brain morphology of childhood aggressive behavior: A multi-informant study in school-age children.

PubMed

Thijssen, Sandra; Ringoot, Ank P; Wildeboer, Andrea; Bakermans-Kranenburg, Marian J; El Marroun, Hanan; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; van IJzendoorn, Marinus H; White, Tonya

2015-09-01

Few studies have focused on the neuroanatomy of aggressive behavior in children younger than 10 years. Here, we explored the neuroanatomical correlates of aggression in a population-based sample of 6- to 9-year-old children using a multiple-informant approach. Magnetic resonance (MR) scans were acquired from 566 children from the Generation R study who participated in the Berkeley Puppet Interview and whose parents had completed the Child Behavior Checklist. Linear regression analyses were used to examine associations between aggression and amygdala and hippocampal volume. We performed surface-based analyses to study the association between aggression and cortical thickness, surface area, and gyrification. Aggressive behavior was associated with smaller amygdala (p < .05) but not hippocampal volume. Aggression was associated with a thinner cortex in the left precentral cortex (p < .01) and in a cluster including the right inferior parietal, supramarginal, and postcentral cortex (p < .001). Gender moderated the association between aggression and cortical thickness in the right medial posterior cortex (p = .001) and the right prefrontal cortex (p < .001). Aggression was associated with decreased gyrification in a large cluster including the right precentral, postcentral, frontal, and parietal cortex (p = .01). Moreover, aggression was associated with decreased gyrification in the right occipital and parietal cortex (p = .02). We found novel evidence that childhood aggressive behavior is related to decreased amygdala volume, decreased sensorimotor cortical thickness, and decreased global right hemisphere gyrification. Aggression is related to cortical thickness in regions associated with the default mode network, with negative associations in boys and positive associations in girls.

Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver Disease and Renal Function among Normal Weight Subjects

PubMed Central

Oniki, Kentaro; Saruwatari, Junji; Izuka, Tomoko; Kajiwara, Ayami; Morita, Kazunori; Sakata, Misaki; Otake, Koji; Ogata, Yasuhiro; Nakagawa, Kazuko

2015-01-01

In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the risk of NAFLD and/or renal dysfunction; however, the influence of the weight status on the associations remains unknown. We aimed to clarify the associations of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while also paying careful attention to the weight status of the subjects. Cross-sectional and retrospective longitudinal studies with 5.5 ± 1.1 years of follow-up were conducted in 740 and 393 Japanese participants (61.2 ± 10.5 and 67.5 ± 6.0 years), respectively, during a health screening program. Among 591 subjects who did not have a habitual alcohol intake and/or hepatitis B or C virus infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in normal weight subjects [odds ratio (95% CI): 3.06 (1.11–8.43), P < 0.05]. Among all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a lower eGFR than those of the C/C genotype [partial regression coefficient (SE): -3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal analyses. Among the overweight subjects, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses; however, the power of the analyses was small, especially in the analyses among overweight subjects. The findings of this study suggest that carriers of the PNPLA3 G/G genotype with a normal weight status should nevertheless be carefully monitored for the presence of NAFLD and/or renal dysfunction. PMID:26200108

Physical inactivity mediates the association between the perceived exercising behavior of social network members and obesity: a cross-sectional study.

PubMed

Leroux, Janette S; Moore, Spencer; Richard, Lucie; Gauvin, Lise

2012-01-01

Social networks influence the spread of depression, health behaviors, and obesity. The social networks of older urban-dwelling adults were examined to assess whether physical inactivity mediated the association between social networks and obesity. Data come from the Montreal Neighborhood Networks and Healthy Aging study (n=2707). Self-reported height and weight were used to calculate body mass index (BMI) with obesity defined as a BMI ≥ 30. A name generator/interpreter instrument was used to elicit participants' core ties (i.e., alters), and assess whether alters exercised regularly and resided in participants' neighborhoods. The International Physical Activity Questionnaire was used to measure physical inactivity. Separate multilevel logistic regression analyses were conducted for younger (18-54 years) and older (55 years plus) age groups to examine the association between the exercising behavior of alters and obesity. Ancillary analyses examined whether the residential location of alters was associated with obesity. Mediation analyses assessed whether physical inactivity mediated the association between alter exercising behavior and obesity. Models adjusted for participant socio-demographic and -economic characteristics. Among the older age stratum (55 years plus), physically inactive individuals were more likely obese (OR 2.14; 95% CIs: 1.48-3.10); participants who had more exercising alters were less likely obese (OR: 0.85; 95% CIs: 0.72-0.99). Physical inactivity mediated the association between exercising alters and obesity. Ancillary analyses showed that having exercising alters in the neighborhood compared to other locations tended to reduce the odds of obesity. This work demonstrates the importance of social networks among older adults in facilitating a physically active lifestyle and reducing the odds of obesity. Such findings can inform the design of public health interventions that seek to improve the environmental conditions supporting the physical activity of older adults.

Whole exome sequence-based association analyses of plasma amyloid-β in African and European Americans; the Atherosclerosis Risk in Communities-Neurocognitive Study.

PubMed

Simino, Jeannette; Wang, Zhiying; Bressler, Jan; Chouraki, Vincent; Yang, Qiong; Younkin, Steven G; Seshadri, Sudha; Fornage, Myriam; Boerwinkle, Eric; Mosley, Thomas H

2017-01-01

We performed single-variant and gene-based association analyses of plasma amyloid-β (aβ) concentrations using whole exome sequence from 1,414 African and European Americans. Our goal was to identify genes that influence plasma aβ42 concentrations and aβ42:aβ40 ratios in late middle age (mean = 59 years), old age (mean = 77 years), or change over time (mean = 18 years). Plasma aβ measures were linearly regressed onto age, gender, APOE ε4 carrier status, and time elapsed between visits (fold-changes only) separately by race. Following inverse normal transformation of the residuals, seqMeta was used to conduct race-specific single-variant and gene-based association tests while adjusting for population structure. Linear regression models were fit on autosomal variants with minor allele frequencies (MAF)≥1%. T5 burden and Sequence Kernel Association (SKAT) gene-based tests assessed functional variants with MAF≤5%. Cross-race fixed effects meta-analyses were Bonferroni-corrected for the number of variants or genes tested. Seven genes were associated with aβ in late middle age or change over time; no associations were identified in old age. Single variants in KLKB1 (rs3733402; p = 4.33x10-10) and F12 (rs1801020; p = 3.89x10-8) were significantly associated with midlife aβ42 levels through cross-race meta-analysis; the KLKB1 variant replicated internally using 1,014 additional participants with exome chip. ITPRIP, PLIN2, and TSPAN18 were associated with the midlife aβ42:aβ40 ratio via the T5 test; TSPAN18 was significant via the cross-race meta-analysis, whereas ITPRIP and PLIN2 were European American-specific. NCOA1 and NT5C3B were associated with the midlife aβ42:aβ40 ratio and the fold-change in aβ42, respectively, via SKAT in African Americans. No associations replicated externally (N = 725). We discovered age-dependent genetic effects, established associations between vascular-related genes (KLKB1, F12, PLIN2) and midlife plasma aβ levels, and identified a plausible Alzheimer's Disease candidate gene (ITPRIP) influencing cell death. Plasma aβ concentrations may have dynamic biological determinants across the lifespan; plasma aβ study designs or analyses must consider age.

Partners or Partners in Crime? The Relationship Between Criminal Associates and Criminogenic Thinking.

PubMed

Whited, William H; Wagar, Laura; Mandracchia, Jon T; Morgan, Robert D

2017-04-01

Meta-analyses examining the risk factors for recidivism have identified the importance of ties with criminal associates as well as thoughts and attitudes conducive to the continuance of criminal behavior (e.g., criminogenic thinking). Criminologists have theorized that a direct relationship exists between the association with criminal peers and the development of criminogenic thinking. The present study empirically explored the relationship between criminal associates and criminogenic thinking in 595 adult male inmates in the United States. It was hypothesized that the proportion of free time spent with and number of criminal associates would be associated with criminogenic thinking, as measured by two self-report instruments, the Measure of Offender Thinking Styles-Revised (MOTS-R) and the Psychological Inventory of Criminal Thinking Styles (PICTS). Hierarchal linear regression analyses demonstrated that the proportion of free time spent with criminal associates statistically predicted criminogenic thinking when controlling for demographic variables. The implications of these findings on correctional practice (including assessment and intervention) as well as future research are discussed.

Association of Acculturation and Health Literacy with Prevalent Dysglycemia and Diabetes Control Among Latinos in the Boston Area Community Health (BACH) Survey.

PubMed

López, Lenny; Grant, Richard W; Marceau, Lisa; Piccolo, Rebecca; McKinlay, John B; Meigs, James B

2016-12-01

This study assessed the effect of acculturation on type 2 diabetes and whether health literacy may mediate this association. The Boston Area Community Health cohort is a multi-stage stratified random sample of adults from Boston including 744 Latinos. We defined dysglycemia as a HbA1c ≥5.7 %. Multivariable analyses examined the associations between acculturation and health literacy adjusting for demographic and clinical variables. Similar analyses were performed among participants with HbA1c ≥7.0 % to assess the association between acculturation and diabetes control. Among an insured primarily foreign born Spanish speaking Latino population, with a long residence period in the US and good healthcare utilization, higher levels of acculturation were not associated with dysglycemia. Lower levels of acculturation were associated with worse diabetes control. Health literacy level did not modify these associations. Elucidating the components of heterogeneity among Latinos will be essential for understanding the influence of acculturation on diabetes.

MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample

PubMed Central

2012-01-01

Background Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. Methods We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. Results When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. Conclusions The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease. PMID:23116433

MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample.

PubMed

Zhao, Jinying; Forsberg, Christopher W; Goldberg, Jack; Smith, Nicholas L; Vaccarino, Viola

2012-11-02

Atherosclerosis is a complex process involving both genetic and epigenetic factors. The monoamine oxidase A (MAOA) gene regulates the metabolism of key neurotransmitters and has been associated with cardiovascular risk factors. This study investigates whether MAOA promoter methylation is associated with atherosclerosis, and whether this association is confounded by familial factors in a monozygotic (MZ) twin sample. We studied 84 monozygotic (MZ) twin pairs drawn from the Vietnam Era Twin Registry. Carotid intima-media thickness (IMT) was measured by ultrasound. DNA methylation in the MAOA promoter region was quantified by bisulfite pyrosequencing using genomic DNA isolated from peripheral blood leukocytes. The association between DNA methylation and IMT was first examined by generalized estimating equation, followed by matched pair analyses to determine whether the association was confounded by familial factors. When twins were analyzed as individuals, increased methylation level was associated with decreased IMT at four of the seven studied CpG sites. However, this association substantially reduced in the matched pair analyses. Further adjustment for MAOA genotype also considerably attenuated this association. The association between MAOA promoter methylation and carotid IMT is largely explained by familial factors shared by the twins. Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment. Clarification of familial factors associated with DNA methylation and early atherosclerosis will provide important information to uncover clinical correlates of disease.

Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

PubMed

Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

2016-11-01

Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

Are personality disorders associated with social welfare burden in the United States?

PubMed

Vaughn, Michael G; Fu, Quana; Beaver, Devin; DeLisi, Matt; Perron, Brian; Howard, Matthew

2010-12-01

This study examined the association between personality disorders and use of major social welfare services in a nationally representative sample of U.S. adults (N = 43,093). Social welfare services received and diagnoses of personality, substance use, mood, and anxiety disorders were assessed with the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV-version. Analyses quantified the association between personality disorders and forms of public assistance while controlling for numerous confounds. Logistic regression analyses revealed dependent personality disorder, paranoid personality disorder, antisocial personality disorder, and avoidant personality disorder were significantly associated with increased odds of receiving public assistance. In contrast, persons diagnosed with histrionic, schizoid, and obsessive-personality disorder were not significantly more likely to receive any public welfare service. Development of effective prevention and treatment of personality disorders would likely lead to reductions in overall social welfare burden.

Power considerations for λ inflation factor in meta-analyses of genome-wide association studies.

PubMed

Georgiopoulos, Georgios; Evangelou, Evangelos

2016-05-19

The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor (λ) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0·001 to 0·5 and λ was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real λ values) and (ii) selected scenario from simulation parameter modification. Adjustment for λ was considered under single correction (within study corrected standard errors) and double correction (additional λ corrected summary estimate). MAF was a pivotal determinant of observed power. In random λ scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF 1·2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.

Increased prevalence of low back pain among physiotherapy students compared to medical students.

PubMed

Falavigna, Asdrubal; Teles, Alisson Roberto; Mazzocchin, Thaís; de Braga, Gustavo Lisbôa; Kleber, Fabrício Diniz; Barreto, Felipe; Santin, Juliana Tosetto; Barazzetti, Daniel; Lazzaretti, Lucas; Steiner, Bruna; Beckenkamp, Natália Laste

2011-03-01

Some studies have demonstrated that physiotherapists have a high prevalence of low back pain (LBP). The association between physiotherapy students, who are potentially exposed to the same LBP occupational risks as graduates, and LBP has never been demonstrated. The objective of the study is to evaluate the association between undergraduate physiotherapy study and LBP. The study design includes a cross-sectional study. A questionnaire-based study was carried out with physiotherapy and medical students. LBP was measured as lifetime, 1-year and point prevalence. Bivariate and multivariate analyses were performed to find the factors associated with LBP. Bivariate analyses were also performed to assess differences between LBP characteristics in the two courses. 77.9% of the students had LBP at some point in their lives, 66.8% in the last year and 14.4% of them reported they were suffering from LBP at the moment of answering the questionnaire. Physiotherapy students reported a higher prevalence of LBP when compared with the medical students in all measures. In the logistic regression model, physiotherapy students (A-OR 2.51; 95% CI 1.35-4.67; p = 0.003), and being exposed to the undergraduate study for more than four semesters (A-OR 2.55; 95% CI 1.43-4.55; p = 0.001) were independently associated with LBP. There were no differences between the courses concerning pain intensity and disability. As it was a cross-sectional study, we were not able to observe accurately if there is an increasing incidence of LBP during the course. Also, we did not intend to identify which activities in the course were associated with the development of LBP. This study clearly demonstrated an association between undergraduate physiotherapy study and LBP. The length of course exposure is also associated with LBP.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

PubMed Central

Vimaleswaran, Karani S; Cavadino, Alana; Berry, Diane J; Jorde, Rolf; Dieffenbach, Aida Karina; Lu, Chen; Alves, Alexessander Couto; Heerspink, Hiddo J Lambers; Tikkanen, Emmi; Eriksson, Joel; Wong, Andrew; Mangino, Massimo; Jablonski, Kathleen A; Nolte, Ilja M; Houston, Denise K; Ahluwalia, Tarunveer Singh; van der Most, Peter J; Pasko, Dorota; Zgaga, Lina; Thiering, Elisabeth; Vitart, Veronique; Fraser, Ross M; Huffman, Jennifer E; de Boer, Rudolf A; Schöttker, Ben; Saum, Kai-Uwe; McCarthy, Mark I; Dupuis, Josée; Herzig, Karl-Heinz; Sebert, Sylvain; Pouta, Anneli; Laitinen, Jaana; Kleber, Marcus E; Navis, Gerjan; Lorentzon, Mattias; Jameson, Karen; Arden, Nigel; Cooper, Jackie A; Acharya, Jayshree; Hardy, Rebecca; Raitakari, Olli; Ripatti, Samuli; Billings, Liana K; Lahti, Jari; Osmond, Clive; Penninx, Brenda W; Rejnmark, Lars; Lohman, Kurt K; Paternoster, Lavinia; Stolk, Ronald P; Hernandez, Dena G; Byberg, Liisa; Hagström, Emil; Melhus, Håkan; Ingelsson, Erik; Mellström, Dan; Ljunggren, Östen; Tzoulaki, Ioanna; McLachlan, Stela; Theodoratou, Evropi; Tiesler, Carla M T; Jula, Antti; Navarro, Pau; Wright, Alan F; Polasek, Ozren; Hayward, Caroline; Wilson, James F; Rudan, Igor; Salomaa, Veikko; Heinrich, Joachim; Campbell, Harry; Price, Jacqueline F; Karlsson, Magnus; Lind, Lars; Michaëlsson, Karl; Bandinelli, Stefania; Frayling, Timothy M; Hartman, Catharina A; Sørensen, Thorkild I A; Kritchevsky, Stephen B; Langdahl, Bente Lomholt; Eriksson, Johan G; Florez, Jose C; Spector, Tim D; Lehtimäki, Terho; Kuh, Diana; Humphries, Steve E; Cooper, Cyrus; Ohlsson, Claes; März, Winfried; de Borst, Martin H; Kumari, Meena; Kivimaki, Mika; Wang, Thomas J; Power, Chris; Brenner, Hermann; Grimnes, Guri; van der Harst, Pim; Snieder, Harold; Hingorani, Aroon D; Pilz, Stefan; Whittaker, John C; Järvelin, Marjo-Riitta; Hyppönen, Elina

2015-01-01

Summary Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97−0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96−0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study. PMID:24974252

Understanding the role of personality in explaining associations between marital quality and parenting

PubMed Central

Ganiban, Jody M.; Ulbricht, Jennifer A.; Spotts, Erica L.; Lichtenstein, Paul; Reiss, David; Hansson, Kjell; Neiderhiser, Jenae M.

2010-01-01

This study examined the contributions of personality to the emotional and behavior dynamics of families. Analyses assessed the degrees to which personality accounts for associations between marital quality and parenting, and mediates genetic contributions to these relationships. Participants included 318 male and 544 female same-sex twin pairs from the Twin and Offspring Study in Sweden. All twins completed self-report measures of marital quality and personality (anxiousness, aggression, sociability). Composite measures of parent negativity and warmth were derived from the twins' and their adolescent children's ratings of the twins' disciplinary styles and the emotional tone of the parent-child relationship. Observational ratings of marital quality and parenting were also obtained for a subset of twins. Analyses indicated that personality characteristics explain 33% to 42% of the covariance between reported marital quality and parenting, and 26% to 28% of the covariance between observed marital quality and parenting. For both sets of analyses personality accounted for more than half of the genetic contributions to covariance between marital quality and parenting. Results indicate that personality significantly contributes to associations between marital quality and parenting, and that personality is an important path through which genetic factors contribute to family relationships. PMID:19803601

Somatic Complaints in Adolescence and Labour Market Participation in Young Adulthood.

PubMed

Winding, Trine Nøhr; Andersen, Johan Hviid

2018-05-01

The primary aim was to investigate the association between somatic symptoms at ages 15 or 18 and reduced labour market participation at age 23, when socioeconomic, social, and mental health risk factors were taken into account. The study included 3223 participants from the West Jutland Cohort Study with questionnaire information on somatic symptoms at ages 15 or 18 and with register information on labour market participation at age 23, gathered from a national register on all public transfer benefits for a 52-week period. The analyses included additional information about socioeconomic background, number of negative life events, social climate in the family, social relations with friends, and depressive symptoms. Logistic regression analyses yielded odds ratios with 95% confidence intervals. Among the males, associations between reporting somatic symptoms at age 18 and low labour market participation was seen in both crude and adjusted analyses (odds ratio: 1.66; 95% confidence intervals: 1.01-2.75), whereas the association among the females disappeared after adjustments (odds ratio: 0.97; 95% confidence intervals: 0.63-1.52). The males that reported somatic symptoms in late adolescence appeared to be the most vulnerable to future reduced labour market participation.

Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma

PubMed Central

Danford, Ian D.; Verkuil, Lana D.; Choi, Daniel J.; Collins, David W.; Gudiseva, Harini V.; Uyhazi, Katherine E.; Lau, Marisa K.; Kanu, Levi N.; Grant, Gregory R.; Chavali, Venkata R.M.; O’Brien, Joan M.

2017-01-01

Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the “POAGome.” We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG. PMID:28223208

Phthalate esters and childhood asthma: A systematic review and congener-specific meta-analysis.

PubMed

Li, Ming-Chieh; Chen, Chi-Hsien; Guo, Yue Leon

2017-10-01

Exposure to phthalate esters (PAEs) has been associated with childhood asthma, but the congener-specific effects of PAEs on childhood asthma were unclear. We aimed to systematically review and meta-analyze observational studies on the associations between specific effects of PAEs and the risk of childhood asthma. Relevant studies were identified by searching three databases up to October 20, 2016. The reference lists of the retrieved articles were also reviewed. We included observational studies that reported risk estimates with 95% confidence intervals (CIs) for the associations between phthalate exposure and the risk of childhood asthma. Fixed-effects models were generally applied to calculate pooled risk estimates. When heterogeneity was present, random-effects models were applied. A total of nine studies featuring 43 data points were included in our final meta-analyses. Results indicated that the benzyl butyl phthalate (BBzP) exposure had a significant association with the risk of childhood asthma. The Odd Ratios (ORs) were from 1.39 to 1.41 for different combination strategies. Subgroup analyses by different exposure period or samples used showed that prenatal exposure to BBzP had a stronger association with the risk of childhood asthma (OR = 1.38, 95% CI = 1.09-1.75), compared to those with postnatal exposure. Besides, the association was evident when the phthalate exposure was measured from dust samples. The OR for the associations between di-2-ethylhexyl phthalate (DEHP) in dust and childhood asthma was 2.71 (95% CI = 1.39-5.28), and 2.08 (95% CI = 1.10-3.92) for BBzP. Our study suggested a positive association between DEHP and BBzP exposure and childhood asthma. Future studies are warranted to identify the underlying mechanisms of the association. Copyright © 2017 Elsevier Ltd. All rights reserved.

Further evidence for the association between LRP8 and schizophrenia.

PubMed

Xiao, Xiao; Yu, Hao; Li, Jun; Wang, Lu; Li, Lingyi; Chang, Hong; Zhang, Dai; Yue, Weihua; Li, Ming

2017-05-08

Previous studies (including genome-wide association study (GWAS) and candidate gene studies) have revealed the important roles of genetic risk factors in schizophrenia, and RELN has been identified as a risk gene for this illness. We recently found that the low-density lipoprotein receptor-related protein 8 (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly associated with schizophrenia and bipolar disorder in European populations. To further enhance our understanding of its role in the risk of psychiatric illnesses, we conducted meta-analyses of a higher density of single nucleotide polymorphisms (SNPs, N=173) in LRP8 to understand their associations with schizophrenia in much larger samples (39,400 cases and 50,357 controls) from populations of European, Chinese and African American ancestries. The significant risk SNPs then underwent further analyses to understand their correlations with bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed that rs5177 in the 3' untranslated region (3'UTR) of LRP8 was associated with schizophrenia and other psychiatric disorders, and rs5177 was also associated with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia susceptibility gene, and suggest that this variant is likely a risk locus in general populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Physical Activity and Anthropometric Characteristics Among Urban Youth in Mexico: A Cross-Sectional Study.

PubMed

Parker, Nathan; Atrooshi, Darran; Lévesque, Lucie; Jauregui, Edtna; Barquera, Simón; Taylor, Juan Lopez Y; Lee, Rebecca E

2016-10-01

Obesity is a critical problem among Mexican youth, but few studies have investigated associations among physical activity (PA) modes and anthropometrics in this population. This study examined associations among active commuting to school (ACS), sports or other organized PA, outdoor play, and body mass index (BMI) percentile and waist circumference (WC) among Mexican youth. Parents of school children (N = 1996, ages 6 to 14 years, 53.1% female) in 3 Mexican cities reported PA participation using the (modified) fourth grade School Physical Activity and Nutrition Survey. Trained assessors measured BMI percentile and WC in person. Parents reported that 52.3% of children engaged in ACS, 57.3% participated in sports or organized PA, and a median of 2 days in the previous week with at least 30 minutes of outdoor play. In complete case analyses (n = 857), ACS was negatively associated with BMI percentile, and outdoor play was negatively associated with WC after adjusting for school, age, sex, and income. In analyses incorporating data from multiple imputation (N = 1996), outdoor play was negatively associated with WC (all Ps < . 05). ACS and outdoor play are favorably associated with anthropometrics and may help prevent childhood obesity in Mexico. ACS and outdoor play should be priorities for increasing youth PA in Mexico.

Occupational asphalt is not associated with head and neck cancer.

PubMed

Fogleman, E V; Eliot, M; Michaud, D S; Nelson, H H; McClean, M D; Langevin, S M; Kelsey, K T

2015-10-01

Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). To better elucidate this relationship by including known risk factors in a large case-control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever-smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A Daily Process Examination of the Temporal Association Between Alcohol Use and Verbal and Physical Aggression in Community Couples

PubMed Central

Testa, Maria; Derrick, Jaye L.

2014-01-01

Alcohol use has been associated with intimate partner aggression perpetration and victimization; however, much of the evidence is based on survey research. Few studies have addressed the proximal effects of drinking episodes on the subsequent occurrence of partner aggression. The current study used daily diary methodology to consider the daily and temporal association between drinking episodes and episodes of partner verbal and physical aggression among a community sample of married and cohabiting couples (N = 118). Male and female partners each provided 56 days of independent daily reports of drinking and partner conflict episodes, including verbal and physical aggression, using interactive voice response technology. Dyadic data analyses, guided by the actor-partner interdependence model, were conducted using hierarchical generalized linear modeling with multivariate outcomes. Daily analyses revealed that alcohol consumption was associated with perpetration of verbal and physical aggression the same day, but not with victimization. Temporal analyses revealed that the likelihood of perpetrating verbal and physical aggression, and the likelihood of being verbally and physically victimized, increased significantly when alcohol was consumed in the previous four hours. Findings did not differ according to gender of perpetrator or victim, and the interaction between perpetrator and victim's alcohol use was not significant in any analysis. The study provides clear evidence that, within a sample of community couples without substance-use disorders or other psychopathology, alcohol consumption by men and women contributes to the occurrence of partner aggression episodes. PMID:24341618

The influence of endometriosis-related symptoms on work life and work ability: a study of Danish endometriosis patients in employment.

PubMed

Hansen, Karina E; Kesmodel, Ulrik S; Baldursson, Einar B; Schultz, Rikke; Forman, Axel

2013-07-01

Little is known about the implications of endometriosis on women's work life. This study aimed at examining the relation between endometriosis-related symptoms and work ability in employed women with endometriosis. In a cohort study, 610 patients with diagnosed endometriosis and 751 reference women completed an electronic survey based on the Endometriosis Health Profile 30-questionnaire and the Work Ability Index (short form). Percentages were reported for all data. Binary and multivariate logistic regression analyses were used to assess risk factors for low work ability. The level of statistical significance was set at p<0.025 in all analyses. In binary analyses a diagnosis of endometriosis was associated with more sick days, work disturbances due to symptoms, lower work ability and a wide number of other implications on work life in employed women. Moreover, a higher pain level and degree of symptoms were associated with low work ability. Full regression analysis indicated that tiredness, frequent pain, a higher daily pain level, a higher number of sick days and feeling depressed at work were associated with low work ability. A long delay from symptom onset to diagnosis was associated with low work ability. These data indicate a severe impact of endometriosis on the work ability of employed women with endometriosis and add to the evidence that this disease represents a significant socio-economic burden. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Gaseous Air Pollution and the Risk for Stroke Admissions: A Case-Crossover Study in Beijing, China.

PubMed

Huang, Fangfang; Luo, Yanxia; Tan, Peng; Xu, Qin; Tao, Lixin; Guo, Jin; Zhang, Feng; Xie, Xueqin; Guo, Xiuhua

2017-02-14

Background: Though increasing evidence supports association between gaseous air pollution and stroke, it remains unclear whether the effects differ in season, sex and age. The aim of this study was to examine the associations of gaseous air pollution with stroke admissions in Beijing, 2013-2014 in different subgroups. Methods: Case-crossover design and conditional logistic regression were used to perform the analyses. We examined the exposure-response relationship between air pollution and stroke. Stratified analyses were performed in different seasons, sex, and age groups. Results: There were 147,624 stroke admissions during the study period. In the whole study period, percent changes of stroke admissions were 0.82% (95% CI: 0.52% to 1.13%) and 0.73% (95% CI: 0.44% to 1.03%) per 10 μg/m³ increase in the same day conentration of nitrogen dioxide (NO₂) and sulfur dioxide (SO₂). The positive associations were higher in warm seasons and with patients >65 years ( p < 0.05). Contrary effects of carbon monoxide (CO) and ozone on stroke admissions were observed in different seasons. Conclusions: NO₂ and SO₂ were positively associated with stroke admissions, with stronger effects in warm seasons and with patients >65 years. The associations of CO and ozone with stroke admissions differed across seasons.

Neighbourhood social capital as a moderator between individual cognitions and sports behaviour among Dutch adolescents.

PubMed

Prins, R G; Beenackers, M A; Boog, M C; Van Lenthe, F J; Brug, J; Oenema, A

2014-03-01

This study aimed to explore whether individual cognitions and neighbourhood social capital strengthen each other in their relation with engaging in sports at least three times per week. Cross-sectional analyses on data from the last wave of the YouRAction trial (2009-2010, Rotterdam, the Netherlands; baseline response: 98%) were conducted. In total 1129 had data on the last wave questionnaire (93%) and 832 of them had complete data on a self-administered questionnaire on frequency of sports participation, perceived neighbourhood social capital, cognitions (attitude, subjective norm, perceived behavioural control and intention toward sport participation) and demographics. Ecometric methods were used to aggregate perceived neighbourhood social capital to the neighbourhood level. Multilevel logistic regression analyses (neighbourhood and individual as levels) were conducted to examine associations of cognitions, neighbourhood social capital and the social capital by individual cognition interaction with fit norm compliance. If the interaction was significant, simple slopes analyses were conducted to decompose interaction effects. It was found that neighbourhood social capital was significantly associated with fit norm compliance (OR: 5.40; 95% CI: 1.13-25.74). Moreover, neighbourhood social capital moderated the association of attitude, perceived behavioural control and intention with fit norm compliance. The simple slope analyses visualized that the associations of cognitions with fit norm compliance were stronger in case of more neighbourhood social capital. Hence, higher levels of neighbourhood social capital strengthen the associations of attitude, perceived behavioural control and intention in their association with fit norm compliance. Copyright © 2014 Elsevier Ltd. All rights reserved.

ParallABEL: an R library for generalized parallelization of genome-wide association studies.

PubMed

Sangket, Unitsa; Mahasirimongkol, Surakameth; Chantratita, Wasun; Tandayya, Pichaya; Aulchenko, Yurii S

2010-04-29

Genome-Wide Association (GWA) analysis is a powerful method for identifying loci associated with complex traits and drug response. Parts of GWA analyses, especially those involving thousands of individuals and consuming hours to months, will benefit from parallel computation. It is arduous acquiring the necessary programming skills to correctly partition and distribute data, control and monitor tasks on clustered computers, and merge output files. Most components of GWA analysis can be divided into four groups based on the types of input data and statistical outputs. The first group contains statistics computed for a particular Single Nucleotide Polymorphism (SNP), or trait, such as SNP characterization statistics or association test statistics. The input data of this group includes the SNPs/traits. The second group concerns statistics characterizing an individual in a study, for example, the summary statistics of genotype quality for each sample. The input data of this group includes individuals. The third group consists of pair-wise statistics derived from analyses between each pair of individuals in the study, for example genome-wide identity-by-state or genomic kinship analyses. The input data of this group includes pairs of SNPs/traits. The final group concerns pair-wise statistics derived for pairs of SNPs, such as the linkage disequilibrium characterisation. The input data of this group includes pairs of individuals. We developed the ParallABEL library, which utilizes the Rmpi library, to parallelize these four types of computations. ParallABEL library is not only aimed at GenABEL, but may also be employed to parallelize various GWA packages in R. The data set from the North American Rheumatoid Arthritis Consortium (NARAC) includes 2,062 individuals with 545,080, SNPs' genotyping, was used to measure ParallABEL performance. Almost perfect speed-up was achieved for many types of analyses. For example, the computing time for the identity-by-state matrix was linearly reduced from approximately eight hours to one hour when ParallABEL employed eight processors. Executing genome-wide association analysis using the ParallABEL library on a computer cluster is an effective way to boost performance, and simplify the parallelization of GWA studies. ParallABEL is a user-friendly parallelization of GenABEL.

Tea consumption and risk of type 2 diabetes mellitus: a systematic review and meta-analysis update

PubMed Central

Yang, Jian; Mao, Qun-Xia; Xu, Hong-Xia; Ma, Xu; Zeng, Chun-Yu

2014-01-01

Objective Tea has been suggested to decrease blood glucose levels and protect pancreatic β cells in diabetic mice. However, human epidemiological studies showed inconsistent results for the association between tea consumption and type 2 diabetes mellitus (T2DM) risk. The aim of this study was to conduct a meta-analysis to further explore the association between tea consumption and incidence of T2DM. Design Systematic review and meta-analysis. Methods We performed a systematic literature search up to 30 August 2013 in PubMed, EMBASE, Chinese Wanfang Database and CNKI database. Pooling relative risks (RRs) were estimated by random-effect models. Two kinds of subgroup analyses (according to sex and regions) were performed. Sensitive analyses were performed according to types of tea. Results Overall, no statistically significant relationship between tea consumption and risk of T2DM was found based on 12 eligible studies (pooling RR 0.99, 95% CI 0.95 to 1.03). Compared with the lowest/non-tea group, daily tea consumption (≥3 cups/day) was associated with a lower T2DM risk (RR 0.84, 95% CI 0.73 to 0.97). Subgroup analyses showed a difference between men and women. Overall, the RRs (95% CI) were 0.92 (0.84 to 1.00) for men, and 1.00 (0.96 to 1.05) for women, respectively. Tea consumption of ≥3 cups/day was associated with decreased T2DM risk in women (RR 0.84, 95% CI 0.71 to 1.00). Overall, the RRs (95% CIs) were 0.84 (0.71 to 1.00) for Asians, and 1.00 (0.97 to 1.04) for Americans and Europeans, respectively. No obvious change was found in sensitivity analyses. Conclusions The results suggest that daily tea consumption (≥3 cups/day) is associated with a lower T2DM risk. However, further studies are needed to enrich related evidence, especially with regard to types of tea or sex. PMID:25052177

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk

PubMed Central

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A.; Gupta, Nilesh S.; Tang, Deliang; Rybicki, Benjamin A.

2017-01-01

BACKGROUND Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias towards the null in epidemiologic studies of over-all risk. METHODS Within a cohort of 6,692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. RESULTS Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95% CI 1.01, 1.97) and obese status (OR = 1.59; 95% CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95% CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95% CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95% CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. CONCLUSIONS In studies of obesity and PCa, differences in prostate volume cause a bias towards the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. PMID:28349547

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk.

PubMed

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A; Gupta, Nilesh S; Tang, Deliang; Rybicki, Benjamin A

2017-06-01

Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias toward the null in epidemiologic studies of over-all risk. Within a cohort of 6692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP, and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95%CI 1.01, 1.97), and obese status (OR = 1.59; 95%CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95%CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95%CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95%CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. In studies of obesity and PCa, differences in prostate volume cause a bias toward the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. © 2017 Wiley Periodicals, Inc.

The Role of Positive Alcohol Expectancies in Underage Binge Drinking Among College Students

PubMed Central

McBride, Nicole M.; Barrett, Blake; Moore, Kathleen A.; Schonfeld, Lawrence

2014-01-01

Objective This study explored associations between positive alcohol expectancies, demographics, as well as academic status and binge drinking among underage college students. Participants A sample of 1,553 underage college students at three public universities and one college in the southeast who completed the Core Alcohol and Drug Survey in the spring 2013 semester. Methods A series of bivariate analyses and logistic regression models were used to examine associations between demographic and academic status variables as well as positive alcohol expectancies with self-reported binge drinking. Positive alcohol expectancies were examined in multivariable models via two factors derived from principal component analyses. Results Students who endorsed higher agreement of these two emergent factors (Sociability; Sexuality) were more likely to report an occurrence of binge drinking in the past two weeks. Conclusions Study results document associations between positive alcohol expectancies and binge drinking among underage students; implications for prevention and treatment are discussed. PMID:24678848

Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

PubMed Central

Bindman, Samantha W.; Pomerantz, Eva M.; Roisman, Glenn I.

2015-01-01

This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers’ parenting from the NICHD Study of Early Child Care and Youth Development (N = 1,306), analyses revealed that mothers’ autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers’ warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers’ educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement. PMID:26366009

Condomless Sex Among Homeless Youth: The Role of Multidimensional Social Norms and Gender.

PubMed

Barman-Adhikari, Anamika; Hsu, Hsun-Ta; Begun, Stephanie; Portillo, Andrea Perez; Rice, Eric

2017-03-01

Most studies of condomless sex among homeless youth have focused on peer norms, while excluding other potentially pertinent influences. This study explored how different types of relationships contributed to norms about condomless sex and whether such norms were associated with engagement in condomless sex among homeless youth. Additionally, because recent work has noted gender differences in social networks of male and female homeless youth, gender differences in social network norms of condomless sex were also assessed. Egocentric network data were collected from homeless youth accessing services at two drop-in centers in Los Angeles, CA (N = 976). Multivariate analyses (non-stratified and stratified by gender) assessed associations between descriptive, injunctive, and communicative norms and participants' engagement in condomless sex. Multivariate analyses indicated that perception of peer condom use and communication with sexual partners were significantly associated with not engaging in condomless sex. These relationships, however, varied by gender. Implications for interventions are discussed.

Do Children's Executive Functions Account for Associations Between Early Autonomy-Supportive Parenting and Achievement Through High School?

PubMed

Bindman, Samantha W; Pomerantz, Eva M; Roisman, Glenn I

2015-08-01

This study evaluated whether the positive association between early autonomy-supportive parenting and children's subsequent achievement is mediated by children's executive functions. Using observations of mothers' parenting from the NICHD Study of Early Child Care and Youth Development ( N = 1,306), analyses revealed that mothers' autonomy support over the first 3 years of life predicted enhanced executive functions (i.e., inhibition, delay of gratification, and sustained attention) during the year prior to kindergarten and academic achievement in elementary and high school even when mothers' warmth and cognitive stimulation, as well as other factors (e.g., children's early general cognitive skills and mothers' educational attainment) were covaried. Mediation analyses demonstrated that over and above other attributes (e.g., temperament), children's executive functions partially accounted for the association between early autonomy-supportive parenting and children's subsequent achievement.

Study on drug costs associated with COPD prescription medicine in Denmark.

PubMed

Jakobsen, Marie; Anker, Niels; Dollerup, Jens; Poulsen, Peter Bo; Lange, Peter

2013-10-01

Spirometric studies of the general population estimate that 430 000 Danes have chronic obstructive pulmonary disease (COPD). COPD is mainly caused by smoking, and smoking cessation is the most important intervention to prevent disease progression. Cost-of-illness studies conclude that the costs associated with COPD in Denmark are significant, but costs of prescription medicine for COPD were not analysed. To analyse the societal costs associated with prescription medicine for COPD in Denmark. The study was designed as a nationwide retrospective register study of the drug costs (ATC group R03) associated with COPD in the period 2001-2010. Data were retrieved from the Prescription Database, the National Patient Register and the Centralised Civil Register. The population comprised individuals (40+ years) who had at least one prescription of selected R03 drugs and who had been either hospitalised with a COPD diagnosis or had at least one prescription for drugs primarily used for COPD. The study population comprised 166 462 individuals of which 97 916 were alive on 31 December 2010. The average annual drug costs (R03) were DKK 7842 (EUR 1055) per patient in 2010 with total costs of DKK 685 million (EUR 92 million). The average lifetime costs associated with COPD prescription medicine were estimated to be DKK 70 000-75 000 (EUR 9416-10 089) per patient (2010 prices). The costs associated with prescription medicine for COPD in Denmark are significant. © 2012 John Wiley & Sons Ltd.

Associations Across Caregiver and Care Recipient Symptoms: Self-Organizing Map and Meta-analysis.

PubMed

Voutilainen, Ari; Ruokostenpohja, Nora; Välimäki, Tarja

2018-03-19

The main objective of this study was to reveal generalizable associations across caregiver burden (CGB), caregiver depression (CGD), care recipient cognitive ability (CRCA), and care recipient behavioral and psychological symptoms of dementia (BPSD). Studies published between 2004 and 2014 and reporting CGB and/or CGD together with CRCA and/or BPSD were included. Only 95 out of 1,955 studies provided enough data for data clustering with the Self-Organizing Map (SOM) and 27 of them for meta-analyses based on correlation coefficients. Caregiver and care recipient symptoms were not tightly associated with each other, except for the CGB-BPSD interaction at the individual level. SOM emphasized the cluster comprising studies reporting low CGB, low CGD, high CRCA, and few BPSD. Meta-analyses indicated high heterogeneity between the original studies. Relationships between caregiver and care recipient symptoms should be treated as situation-specific phenomena, at least when the symptoms are moderate at most. Dementia caregiving per se should not be understood as a source of stress and mental health problems. More systematic and coherent use of measures is necessary to enable a comprehensive analysis of caregiving.

Selective serotonin reuptake inhibitors and risk of major congenital anomalies for pregnancies in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study.

PubMed

Nishigori, Hidekazu; Obara, Taku; Nishigori, Toshie; Mizuno, Satoshi; Metoki, Hirohito; Hoshiai, Tetsuro; Watanabe, Zen; Sakurai, Kasumi; Ishikuro, Mami; Tatsuta, Nozomi; Nishijima, Ichiko; Fujiwara, Ikuma; Kuriyama, Shinichi; Arima, Takahiro; Nakai, Kunihiko; Yaegashi, Nobuo

2017-05-01

We analyzed data from the Japan Environment and Children's Study (JECS), on the association between selective serotonin reuptake inhibitors (SSRI) use during pregnancy and the risk of developing of major congenital anomalies in Japan. JECS is an ongoing nationwide birth cohort study. The study includes 95 994 single pregnant women and their offspring. Among them, 172 used any SSRI up to the 12 th gestational week. Crude analyses show a significantly increased incidence of upper limb, abdominal, and urogenital abnormalities. In particular, the incidence of microcephaly, hydrencephalus, esophageal atresia, small intestinal atresia, and achondroplasia was significantly higher with than without exposure to these substances. On multivariate analyses, urogenital abnormality was significant (odds ratio 3.227; 95% confidence interval: 1.460-7.134). This Japanese nationwide birth cohort survey clarified that the use of any SSRI until the 12 th gestational week was associated with urogenital abnormality in children. The survey for association with minor classification abnormality needs further examination in Japan. © 2016 Japanese Teratology Society.

Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas

PubMed Central

Montazeri, Zahra; Theodoratou, Evropi; Nyiraneza, Christine; Timofeeva, Maria; Chen, Wanjing; Svinti, Victoria; Sivakumaran, Shanya; Gresham, Gillian; Cubitt, Laura; Carvajal-Carmona, Luis; Bertagnolli, Monica M; Zauber, Ann G; Tomlinson, Ian; Farrington, Susan M; Dunlop, Malcolm G; Campbell, Harry; Little, Julian

2018-01-01

Background Low penetrance genetic variants, primarily single nucleotide polymorphisms, have substantial influence on colorectal cancer (CRC) susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here, we report the first comprehensive field synopsis that catalogues all genetic association studies on CRA, with a parallel online database (http://www.chs.med.ed.ac.uk/CRAgene/). Methods We performed a systematic review, reviewing 9750 titles and then extracted data from 130 publications reporting on 181 polymorphisms in 74 genes. We conducted meta-analyses to derive summary effect estimates for 37 polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False Discovery Probability (BFDP) to assess the levels of the credibility of associations. Results We considered the association with the rs6983267 variant at 8q24 as “highly credible”, reaching genome wide statistical significance in at least one meta-analysis model. We identified “less credible” associations (higher heterogeneity, lower statistical power, BFDP>0.02) with a further four variants of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which positive associations with CRA risk have been previously reported, the meta-analyses revealed no credible evidence to support these as true associations. Conclusions The limited number of credible associations between low penetrance genetic variants and CRA reflects the lower volume of evidence and associated lack of statistical power to detect associations of the magnitude typically observed for genetic variants and chronic diseases. The CRAgene database provides context for CRA genetic association data and will help inform future research directions. PMID:26451011

Should studies of risk factors for musculoskeletal disorders be stratified by gender? Lessons from the 1998 Québec Health and Social Survey.

PubMed

Messing, Karen; Stock, Susan R; Tissot, France

2009-03-01

Several studies have reported male-female differences in the prevalence of symptoms of work-related musculoskeletal disorders (MSD), some arising from workplace exposure differences. The objective of this paper was to compare two strategies analyzing a single dataset for the relationships between risk factors and MSD in a population-based sample with a wide range of exposures. The 1998 Québec Health and Social Survey surveyed 11 735 respondents in paid work and reported "significant" musculoskeletal pain in 11 body regions during the previous 12 months and a range of personal, physical, and psychosocial risk factors. Five studies concerning risk factors for four musculoskeletal outcomes were carried out on these data. Each included analyses with multiple logistic regression (MLR) performed separately for women, men, and the total study population. The results from these gender-stratified and unstratified analyses were compared. In the unstratified MLR models, gender was significantly associated with musculoskeletal pain in the neck and lower extremities, but not with low-back pain. The gender-stratified MLR models identified significant associations between each specific musculoskeletal outcome and a variety of personal characteristics and physical and psychosocial workplace exposures for each gender. Most of the associations, if present for one gender, were also found in the total population. But several risk factors present for only one gender could be detected only in a stratified analysis, whereas the unstratified analysis added little information. Stratifying analyses by gender is necessary if a full range of associations between exposures and MSD is to be detected and understood.

Does age modify the association between psychosocial factors at work and deterioration of self-rated health?

PubMed

Burr, Hermann; Hasselhorn, Hans Martin; Kersten, Norbert; Pohrt, Anne; Rugulies, Reiner

2017-09-01

Objectives Few epidemiological studies have examined whether associations of psychosocial working conditions with risk of poor health differ by age. Based on results from mostly cross-sectional studies, we test whether (i) psychosocial relational factors (social support) are more strongly associated with declining health of older than younger employees and (ii) psychosocial job factors (workpace, influence, possibilities for development) are more strongly associated with declining health of younger than older employees. Methods We extracted two cohorts from the Danish Work Environment Cohort Study (DWECS): the 2000-2005 and 2005-2010 cohorts. The participating 5281 employees with good self-rated health (SRH) at baseline were observed in 6585 5-year time windows. Using log-binomial regression analyses, we analysed whether psychosocial factors at work predicted 5-year deterioration of SRH. Effect modification by age was estimated by calculating relative excess risk due to interaction (RERI). Results High workpace among men, low influence at work as well as low social support from colleagues among women, and low possibilities for development and low social support from supervisors among both genders predicted 5-year decline in SRH. Of the 20 interaction analyses, only 1 was statistically significant and in the opposite direction of what was hypothesized (higher risk for declining SRH among middle-aged men with low possibilities for development compared to the young men with high possibilities for development). Conclusions Psychosocial working conditions predicted decline in SRH in this 5-year follow-up study. The model did not support our hypotheses about modifying effects by age.

Cumulative Risk and Physiological Stress Responses in African American Adolescents.

PubMed

Kliewer, Wendy; Robins, Jo Lynne W

2017-07-01

To investigate associations between components of cumulative risk (CR) and physiological stress responses in African American adolescents and evaluate emotion regulation as a mediator and sex as a moderator of these associations. Cortisol and salivary alpha amylase (sAA) were collected in adolescents ( N = 205; 55% female; 12.1 ± 1.6 years at baseline) as part of a longitudinal study of stress and adjustment in families. CR was assessed at baseline and emotion regulation was assessed at baseline and 2 years later at Wave 3 (W3) using caregiver and adolescent reports. Cortisol and sAA responses to the social competence interview were assessed at W3. Repeated-measures analyses of variance predicting cortisol and controlling for time of day, adolescent age, medication usage, and pubertal status revealed significant interactions of time with both psychosocial and sociodemographic risk. In both analyses, youths with higher levels of risk showed a steeper decline in cortisol than youths with lower levels of risk. In parallel analyses predicting sAA, time interacted with psychosocial but not with sociodemographic risk. There were no interactions with sex in any of the analyses. Although CR was associated with changes in emotion regulation, there was no evidence that these changes accounted for the observed CR-stress response associations. These findings illustrate the potential importance of disentangling CR and suggest that additional work is needed to help explicate why and how CR is associated with specific physiological responses to stress.

Sedentary behaviour and adiposity in youth: a systematic review of reviews and analysis of causality.

PubMed

Biddle, Stuart J H; García Bengoechea, Enrique; Wiesner, Glen

2017-03-28

Sedentary behaviour (sitting time) has becoming a very popular topic for research and translation since early studies on TV viewing in children in the 1980s. The most studied area for sedentary behaviour health outcomes has been adiposity in young people. However, the literature is replete with inconsistencies. We conducted a systematic review of systematic reviews and meta-analyses to provide a comprehensive analysis of evidence and state-of-the-art synthesis on whether sedentary behaviours are associated with adiposity in young people, and to what extent any association can be considered 'causal'. Searches yielded 29 systematic reviews of over 450 separate papers. We analysed results by observational (cross-sectional and longitudinal) and intervention designs. Small associations were reported for screen time and adiposity from cross-sectional evidence, but associations were less consistent from longitudinal studies. Studies using objective accelerometer measures of sedentary behaviour yielded null associations. Most studies assessed BMI/BMI-z. Interventions to reduce sedentary behaviour produced modest effects for weight status and adiposity. Accounting for effects from sedentary behaviour reduction alone is difficult as many interventions included additional changes in behaviour, such as physical activity and dietary intake. Analysis of causality guided by the classic Bradford Hill criteria concluded that there is no evidence for a causal association between sedentary behaviour and adiposity in youth, although a small dose-response association exists. Associations between sedentary behaviour and adiposity in children and adolescents are small to very small and there is little to no evidence that this association is causal. This remains a complex field with different exposure and outcome measures and research designs. But claims for 'clear' associations between sedentary behaviour and adiposity in youth, and certainly for causality, are premature or misguided.

A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood

PubMed Central

Jiang, Jiyang; Thalamuthu, Anbupalam; Ho, Jennifer E.; Mahajan, Anubha; Ek, Weronica E.; Brown, David A.; Breit, Samuel N.; Wang, Thomas J.; Gyllensten, Ulf; Chen, Ming-Huei; Enroth, Stefan; Januzzi, James L.; Lind, Lars; Armstrong, Nicola J.; Kwok, John B.; Schofield, Peter R.; Wen, Wei; Trollor, Julian N.; Johansson, Åsa; Morris, Andrew P.; Vasan, Ramachandran S.; Sachdev, Perminder S.; Mather, Karen A.

2018-01-01

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ∼5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10-35), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the“COPI-mediated anterograde transport” gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction (p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels. PMID:29628937

A Meta-Analysis of Genome-Wide Association Studies of Growth Differentiation Factor-15 Concentration in Blood.

PubMed

Jiang, Jiyang; Thalamuthu, Anbupalam; Ho, Jennifer E; Mahajan, Anubha; Ek, Weronica E; Brown, David A; Breit, Samuel N; Wang, Thomas J; Gyllensten, Ulf; Chen, Ming-Huei; Enroth, Stefan; Januzzi, James L; Lind, Lars; Armstrong, Nicola J; Kwok, John B; Schofield, Peter R; Wen, Wei; Trollor, Julian N; Johansson, Åsa; Morris, Andrew P; Vasan, Ramachandran S; Sachdev, Perminder S; Mather, Karen A

2018-01-01

Blood levels of growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), have been associated with various pathological processes and diseases, including cardiovascular disease and cancer. Prior studies suggest genetic factors play a role in regulating blood MIC-1/GDF-15 concentration. In the current study, we conducted the largest genome-wide association study (GWAS) to date using a sample of ∼5,400 community-based Caucasian participants, to determine the genetic variants associated with MIC-1/GDF-15 blood concentration. Conditional and joint (COJO), gene-based association, and gene-set enrichment analyses were also carried out to identify novel loci, genes, and pathways. Consistent with prior results, a locus on chromosome 19, which includes nine single nucleotide polymorphisms (SNPs) (top SNP, rs888663, p = 1.690 × 10 -35 ), was significantly associated with blood MIC-1/GDF-15 concentration, and explained 21.47% of its variance. COJO analysis showed evidence for two independent signals within this locus. Gene-based analysis confirmed the chromosome 19 locus association and in addition, a putative locus on chromosome 1. Gene-set enrichment analyses showed that the"COPI-mediated anterograde transport" gene-set was associated with MIC-1/GDF15 blood concentration with marginal significance after FDR correction ( p = 0.067). In conclusion, a locus on chromosome 19 was associated with MIC-1/GDF-15 blood concentration with genome-wide significance, with evidence for a new locus (chromosome 1). Future studies using independent cohorts are needed to confirm the observed associations especially for the chromosomes 1 locus, and to further investigate and identify the causal SNPs that contribute to MIC-1/GDF-15 levels.

The Moderating Effect of Parental Warmth on the Association between Spanking and Child Aggression: A Longitudinal Approach

ERIC Educational Resources Information Center

Stacks, Ann Michele; Oshio, Toko; Gerard, Jean; Roe, Jacqueline

2009-01-01

Using data from the Early Head Start Research and Evaluation Study, this study analysed the stability of child aggressive behaviour beginning in infancy and tested whether spanking when the child was 36 months was associated with aggressive child behaviour among three ethnic groups and whether maternal warmth moderated the effect of spanking on…

Computer-Assisted Second Language Vocabulary Learning in a Paired-Associate Paradigm: A Critical Investigation of Flashcard Software

ERIC Educational Resources Information Center

Nakata, Tatsuya

2011-01-01

The present study aims to conduct a comprehensive investigation of flashcard software for learning vocabulary in a second language. Nine flashcard programs were analysed using 17 criteria derived from previous studies on flashcard learning as well as paired-associate learning. Results suggest that in general, most programs have been developed in a…

Predictors of Word-Reading Ability in 7-Year-Olds: Analysis of Data from a U.K. Cohort Study

ERIC Educational Resources Information Center

Russell, Ginny; Ukoumunne, Obioha C.; Ryder, Denise; Golding, Jean; Norwich, Brahm

2018-01-01

Previous U.K. population-based studies have found associations amongst early speech and language difficulties, socioeconomic disadvantage and children's word-reading ability later on. We examine the strength of these associations in a recent U.K. population-based birth cohort. Analyses were based on 13,680 participants. Linear regression models…

Psychological Factors Associated with Development of TMD: the OPPERA Prospective Cohort Study

PubMed Central

Fillingim, Roger B.; Ohrbach, Richard; Greenspan, Joel D.; Knott, Charles; Diatchenko, Luda; Dubner, Ronald; Bair, Eric; Baraian, Cristina; Mack, Nicole; Slade, Gary D.; Maixner, William

2013-01-01

Case-control studies have consistently associated psychological factors with chronic pain in general and with temporomandibular disorders (TMD) specifically. However, only a handful of prospective studies has explored whether pre-existing psychological characteristics represent risk factors for first-onset TMD. The current findings derive from the prospective cohort study of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 3,263 TMD-free participants completed a battery of psychological instruments assessing general psychological adjustment and personality, affective distress, psychosocial stress, somatic symptoms, and pain coping and catastrophizing. Study participants were then followed prospectively for an average of 2.8 years to ascertain cases of first-onset of TMD, and 2,737 provided follow-up data and were considered in the analyses of TMD onset. In bivariate and demographically-adjusted analyses, several psychological variables predicted increased risk of first-onset TMD, including reported somatic symptoms, psychosocial stress, and affective distress. Principal component analysis of 26 psychological scores was used to identify latent constructs, revealing four components: stress and negative affectivity, global psychological and somatic symptoms, passive pain coping, and active pain coping. In multivariable analyses, global psychological and somatic symptoms emerged as the most robust risk factor for incident TMD. These findings provide evidence that measures of psychological functioning can predict first-onset of TMD. Future analyses in the OPPERA cohort will determine whether these psychological factors interact with other variables to increase risk for TMD onset and persistence. PMID:24275225

The Health Impact of Intensive and Nonintensive Grandchild Care in Europe: New Evidence From SHARE

PubMed Central

Glaser, Karen; Tinker, Anthea

2016-01-01

Objectives: Grandparents are an important source of childcare. However, caring for grandchildren may affect grandparents’ health in both positive and negative ways. Our study examines the association between grandparental childcare and grandparents’ health at 2- and 4-year follow-up. Method: Our study is based on grandparents aged 50 and older from Waves 1–4 of the Survey of Health, Ageing and Retirement in Europe (SHARE). Using multivariate analyses, we investigated associations between intensive and nonintensive grandparental childcare at Wave 2 and subsequent health (self-rated health, depressive symptoms, and disability) controlling for covariates and health at baseline. Associations between changes over time in grandparental childcare and health at follow-up were also explored. Multiple imputation techniques and sensitivity analyses were undertaken to investigate possible biases arising from sample attrition. Results: Grandparents looking after grandchildren, whether intensively or nonintensively, experienced some health benefits. Associations strengthened when attrition was accounted for, particularly if it is assumed that those who dropped out of the study were in poor health. Discussion: Our results show better health among grandparents who provided grandchild care in the European countries studied. These results are important given the widespread provision of grandchild care in Europe. PMID:26315046

Association between overweight/obesity and periodontal disease in children and adolescents: a systematic review and meta-analysis.

PubMed

Martens, L; De Smet, S; Yusof, M Y P M; Rajasekharan, S

2017-04-01

To provide a systematic review and meta-analyses investigating the association between overweight/obesity as defined by Body Mass Index (BMI) and periodontal disease in terms of clinical periodontal outcomes. A systematic search of the literature was conducted by two authors (SR and SD) independently in the Cochrane Library, PubMed, Web of Science (ISI), Scopus, Scielo, Lilacs and System for Information on Grey Literature in Europe (SIGLE) for full articles published until September 2015. Studies analysing the association between overweight/obesity as defined by Body Mass Index (BMI) and periodontal disease in children and/or adolescents (age ≤18 years) were included. The Gwets AC1 inter-rater reliability coefficient for screening data was calculated using Agreestat 2011.1. Meta-analyses were carried out by using RStudio version 0.97.551-©2009-2012 RStudio, Inc. software. A total of 769 titles and abstracts were screened and 12 articles met the inclusion criteria for the systematic review while only 7 were selected for meta-analyses. The Gwets AC1 inter-rater reliability coefficient for screening data was excellent (0.98; CI 0.98-0.99). A positive association between overweight/obesity and a number of periodontal diseases was seen. For the association between prevalent periodontal disease and obesity in children, the overall fixed-effects OR and 95% CI was 1.46 (1.20-1.77) with a χ 2 statistic for heterogeneity (Q) of 33.4 with 6 degrees of freedom (P < 0.005). The available evidence suggests a significantly positive association between periodontal disease and obesity in children. Paediatric dentists should be aware of periodontal alterations as a potential hazard associated with obesity.

Hydronephrosis in patients with cervical cancer: an assessment of morbidity and survival

PubMed Central

Patel, Krishna; Foster, Nathan R.; Kumar, Amanika; Grudem, Megan; Longenbach, Sherri; Bakkum-Gamez, Jamie; Haddock, Michael; Dowdy, Sean; Jatoi, Aminah

2015-01-01

Purpose Hydronephrosis is a frequently observed but understudied complication in patients with cervical cancer. To better characterize hydronephrosis in cervical cancer patients, the current study sought (1) to describe hydronephrosis-associated morbidity and (2) to analyze the prognostic effect of hydronephrosis in patients with a broad range of cancer stages over time. Methods The Mayo Clinic Tumor Registry was interrogated for all invasive cervical cancer patients seen at the Mayo Clinic from 2008 through 2013 in Rochester, Minnesota; these patients’ medical records were then reviewed in detail. Results Two hundred seventy-nine cervical cancer patients with a median age of 49 years and a range of cancer stages were included. Sixty-five patients (23 %) were diagnosed with hydronephrosis at some point during their disease course. In univariate analyses, hydronephrosis was associated with advanced cancer stage (p<0.0001), squamous histology (p=0.0079), and nonsurgical cancer treatment (p=0.0039). In multivariate analyses, stage and tumor histology were associated with hydronephrosis. All but one patient underwent stent placement or urinary diversion; hydronephrosis-related morbidity included pain, urinary tract infections, nausea and vomiting, renal failure, and urinary tract bleeding. In landmark univariate survival analyses, hydronephrosis was associated with worse survival at all time points. In landmark multivariate analyses (adjusted for patient age, stage, cancer treatment, and tumor histology), hydronephrosis was associated with a trend toward worse survival over time (hazard ratios ranged from 1.47 to 4.69). Conclusion Hydronephrosis in cervical cancer patients is associated with notable morbidity. It is also associated with trends toward worse survival—even if it occurs after the original cancer diagnosis. PMID:25339620

A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions.

PubMed

Janssens, A Cecile J W; Gwinn, Marta; Bradley, Linda A; Oostra, Ben A; van Duijn, Cornelia M; Khoury, Muin J

2008-03-01

Predictive genomic profiling used to produce personalized nutrition and other lifestyle health recommendations is currently offered directly to consumers. By examining previous meta-analyses and HuGE reviews, we assessed the scientific evidence supporting the purported gene-disease associations for genes included in genomic profiles offered online. We identified seven companies that offer predictive genomic profiling. We searched PubMed for meta-analyses and HuGE reviews of studies of gene-disease associations published from 2000 through June 2007 in which the genotypes of people with a disease were compared with those of a healthy or general-population control group. The seven companies tested at least 69 different polymorphisms in 56 genes. Of the 56 genes tested, 24 (43%) were not reviewed in meta-analyses. For the remaining 32 genes, we found 260 meta-analyses that examined 160 unique polymorphism-disease associations, of which only 60 (38%) were found to be statistically significant. Even the 60 significant associations, which involved 29 different polymorphisms and 28 different diseases, were generally modest, with synthetic odds ratios ranging from 0.54 to 0.88 for protective variants and from 1.04 to 3.2 for risk variants. Furthermore, genes in cardiogenomic profiles were more frequently associated with noncardiovascular diseases than with cardiovascular diseases, and though two of the five genes of the osteogenomic profiles did show significant associations with disease, the associations were not with bone diseases. There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention.

Is healthcare really equal for all? Assessing the horizontal and vertical equity in healthcare utilisation among older Ghanaians.

PubMed

Dei, Vincent; Sebastian, Miguel San

2018-06-20

There is a lack of focused research on the older population in Ghana and about issues pertaining to their access to healthcare services. Furthermore, information is lacking regarding the fairness in the access to these services. This study aimed to ascertain whether horizontal and vertical equity requirements were being met in the healthcare utilisation among older adults aged 50 years and above. This study was based on a secondary cross-sectional data from the World Health Organization's Study on global AGEing (SAGE) and adult health wave 1 conducted from 2007 to 2008 in Ghana. Data on 4304 older adults aged 50 years-plus were analysed. Bivariate and multivariable analyses were carried out to analyse the association between outpatient/inpatient utilisation and (1) socioeconomic status (SES), controlling for need variables (horizontal equity) and (2) need variables, controlling for SES (vertical equity). Odds ratios with 95% confidence intervals were calculated to analyse the association between relevant variables. Horizontal and vertical inequities were found in the utilisation of outpatient services. Inpatient healthcare utilisation was both horizontally and vertically equitable. Women were found to be more likely to use outpatient services than men but had reduced odds of using inpatient services. Possessing a health insurance was also significantly associated with the use of both inpatient and outpatient services. Whilst equity exists in inpatient care utilisation, more needs to be done to achieve equity in the access to outpatient services. The study reaffirms the need to evaluate both the horizontal and vertical dimensions in the assessment of equity in healthcare access. It provides the basis for further research in bridging the healthcare access inequity gap among older adults in Ghana.

Investigating the relationship between iron and depression.

PubMed

Mills, Natalie T; Maier, Robert; Whitfield, John B; Wright, Margaret J; Colodro-Conde, Lucia; Byrne, Enda M; Scott, James G; Byrne, Gerard J; Hansell, Narelle K; Vinkhuyzen, Anna A E; CouvyDuchesne, Baptiste; Montgomery, Grant W; Henders, Anjali K; Martin, Nicholas G; Wray, Naomi R; Benyamin, Beben

2017-11-01

Lower levels of circulating iron have been associated with depression. Our objective was to investigate the phenotypic and genetic relationship between measures of circulating levels of iron (serum iron, transferrin, transferrin saturation, and ferritin) and depressive symptoms. Data were available from ongoing studies at QIMR Berghofer Medical Research Institute (QIMRB), including twin adolescents (mean age 15.1 years, standard deviation (SD) 3.2 years), and twin adults (mean age 23.2 years, SD 2.2 years). In the adolescent cohort, there were 3416 participants from 1688 families. In the adult cohort there were 9035 participants from 4533 families. We estimated heritabilities of, and phenotypic and genetic correlations between, traits. We conducted analyses that linked results from published large-scale genome-wide association studies (including iron and Major Depressive Disorder) with our study samples using single SNP and multi-SNP genetic risk score analyses, and LD score regression analyses. In both cohorts, measures of iron, transferrin, transferrin saturation, and log 10 of ferritin (L10Fer) were all highly heritable, while depressive measures were moderately heritable. In adolescents, depression measures were higher in those in the middle 10th versus top 10th percentile of transferrin saturation measures (p = 0.002). Genetic profile risk scores of the iron measures were not significantly associated with depression in study participants. LD score analyses showed no significant genetic relationship between iron and depression. Genetic factors strongly influence iron measures in adolescents and adults. Using several different strategies we find no evidence for a genetic contribution to the relationship between blood measures of iron and measures of depression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term mobile phone use and acoustic neuroma risk.

PubMed

Pettersson, David; Mathiesen, Tiit; Prochazka, Michaela; Bergenheim, Tommy; Florentzson, Rut; Harder, Henrik; Nyberg, Gunnar; Siesjö, Peter; Feychting, Maria

2014-03-01

There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.