| 1. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 2. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 3. |
- Saxena, Richa, et al.
(författare)
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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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| 4. |
- Wormser, David, et al.
(författare)
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Adult height and the risk of cause-specific death and vascular morbidity in 1 million people : individual participant meta-analysis
- 2012
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 41:5, s. 1419-1433
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.MethodsWe calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies.ResultsFor people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.ConclusionAdult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.
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| 5. |
- Scott, Robert A, et al.
(författare)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Tidskriftsartikel (refereegranskat)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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| 6. |
- Hiyoshi, Ayako, 1972-, et al.
(författare)
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A new theory-based social classification in Japan and its validation using historically collected information
- 2013
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Ingår i: Social Science and Medicine. - Oxford, United Kingdom : Pergamon-Elsevier Ltd.. - 0277-9536 .- 1873-5347. ; 87, s. 84-92
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Tidskriftsartikel (refereegranskat)abstract
- Studies of health inequalities in Japan have increased since the millennium. However, there remains a lack of an accepted theory-based classification to measure occupation-related social position for Japan. This study attempts to derive such a classification based on the National Statistics Socio-economic Classification in the UK. Using routinely collected data from the nationally representative Comprehensive Survey of the Living Conditions of People on Health and Welfare, the Japanese Socioeconomic Classification was derived using two variables - occupational group and employment status. Validation analyses were conducted using household income, home ownership, self-rated good or poor health, and Kessler 6 psychological distress (n ≈ 36,000). After adjustment for age, marital status, and area (prefecture), one step lower social class was associated with mean 16% (p < 0.001) lower income, and a risk ratio of 0.93 (p < 0.001) for home ownership. The probability of good health showed a trend in men and women (risk ratio 0.94 and 0.93, respectively, for one step lower social class, p < 0.001). The trend for poor health was significant in women (odds ratio 1.12, p < 0.001) but not in men. Kessler 6 psychological distress showed significant trends in men (risk ratio 1.03, p = 0.044) and in women (1.05, p = 0.004). We propose the Japanese Socioeconomic Classification, derived from basic occupational and employment status information, as a meaningful, theory-based and standard classification system suitable for monitoring occupation-related health inequalities in Japan.
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| 7. |
- Hiyoshi, Ayako, 1972-, et al.
(författare)
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Health inequalities in Japan : the role of material, psychosocial, social relational and behavioural factors
- 2014
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Ingår i: Social Science and Medicine. - Oxford, United Kingdom : Pergamon-Elsevier Science Ltd. - 0277-9536 .- 1873-5347. ; 104, s. 201-209
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Tidskriftsartikel (refereegranskat)abstract
- The extent that risk factors, identified in Western countries, account for health inequalities in Japan remains unclear. We analysed a nationally representative sample (Comprehensive Survey of Living Conditions surveyed in 2001 (n = 40,243)). The cross-sectional association between self-rated fair or poor health and household income and a theory-based occupational social class was summarised using the relative index of inequality [RII]. The percentage attenuation in RII accounted for by candidate contributory factors - material, psychosocial, social relational and behavioural - was computed. The results showed that the RII for household income based on self-rated fair or poor health was reduced after including the four candidate contributory factors in the model by 20% (95% CI 2.1, 43.6) and 44% (95% CI 18.2, 92.5) in men and women, respectively. The RII for the Japanese Socioeconomic Classification [J-SEC] was reduced, not significantly, by 22% (95% CI -6.3, 100.0) in men in the corresponding model, while J-SEC was not associated with self-rated health in women. Material factors produced the most consistent and strong attenuation in RII for both socioeconomic indicators, while the contributions attributable to behaviour alone were modest. Social relational factors consistently attenuated the RII for both socioeconomic indicators in men whereas they did not make an independent contribution in women. The influence of perceived stress was inconsistent and depended on the socioeconomic indicator used. In summary, social inequalities in self-rated fair or poor health were reduced to a degree by the factors included. The results indicate that the levelling of health across the socioeconomic hierarchy needs to consider a wide range of factors, including material and psychosocial factors, in addition to the behavioural factors upon which the current public health policies in Japan focus. The analyses in this study need to be replicated using a longitudinal study design to confirm the roles of different factors in health inequalities.
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| 8. |
- Hiyoshi, Ayako, 1972-, et al.
(författare)
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Inequalities in self-rated health in Japan 1986-2007 according to household income and a novel occupational classification : national sampling survey series
- 2013
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Ingår i: Journal of Epidemiology and Community Health. - London, United Kingdom : BMJ Publishing Group. - 0143-005X .- 1470-2738. ; 67:11, s. 960-5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Japan, for the past two decades, has seen economic stagnation and substantial social change. We examined whether health inequalities increased over this period.Methods: Using eight triennial waves of a series of large nationally representative surveys between 1986 and 2007 (n=398 303), temporal trends in relative and slope indices of inequality (RII, SII, respectively) were tested based on self-rated health in relation to theory-based social class and household income.Results: Age-standardised prevalence of self-rated fair or poor health showed V-shaped time trends in both sexes with the lowest prevalence in early/mid-1990s. In 1986, RII and SII in household social class and income were significant for both sexes. In men, RII and SII according to income showed significant narrowing of temporal trends in poor health (-1.4% and -0.1% annually, respectively), but these were stable in women. After multilevel multiple imputation for missing income data, the findings in men were not altered but narrowing trends became evident and significant in women (-1% and -0.1% annually, respectively). Inequality indices for social class remained constant over the study period in both sexes.Conclusions: Relative and absolute health inequalities for social class and income based on self-rated fair or poor health narrowed or remained stable between 1986 and 2007, despite the economic stagnation and adverse social changes. Overall population health across socioeconomic groups initially improved but then worsened. The positive finding regarding the health inequality trend seen in the Japanese context is informative for the wider international community during this period of economic uncertainty.
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| 9. |
- Theorell, Töres, et al.
(författare)
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Job Strain as a Risk Factor for Type 2 Diabetes : A Pooled Analysis of 124,808 Men and Women
- 2014
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 37:8, s. 2268-2275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as "job strain," is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06-1.25) with no difference between men and women (1.19 [1.06-1.34] and 1.13 [1.00-1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00-1.23). CONCLUSIONS Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors.
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| 10. |
- Theorell, Töres, et al.
(författare)
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Job strain and cardiovascular disease risk factors : Meta-analysis of individual-participant data from 47,000 men and women
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6, s. e67323-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundJob strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain – heart disease association.Methodology and Principal FindingsWe pooled cross-sectional, individual-level data from eight studies comprising 47,045 participants to investigate the association between job strain and the following cardiovascular disease risk factors: diabetes, blood pressure, pulse pressure, lipid fractions, smoking, alcohol consumption, physical inactivity, obesity, and overall cardiovascular disease risk as indexed by the Framingham Risk Score. In age-, sex-, and socioeconomic status-adjusted analyses, compared to those without job strain, people with job strain were more likely to have diabetes (odds ratio 1.29; 95% CI: 1.11–1.51), to smoke (1.14; 1.08–1.20), to be physically inactive (1.34; 1.26–1.41), and to be obese (1.12; 1.04–1.20). The association between job strain and elevated Framingham risk score (1.13; 1.03–1.25) was attributable to the higher prevalence of diabetes, smoking and physical inactivity among those reporting job strain.ConclusionsIn this meta-analysis of work-related stress and cardiovascular disease risk factors, job strain was linked to adverse lifestyle and diabetes. No association was observed between job strain, clinic blood pressure or blood lipids.
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