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- Arking, D. E., et al.
(author)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Journal article (peer-reviewed)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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- Vasan, Ramachandran S, et al.
(author)
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Genetic variants associated with cardiac structure and function : a meta-analysis and replication of genome-wide association data
- 2009
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:2, s. 168-178
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Journal article (peer-reviewed)abstract
- CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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- Greiser, K. H., et al.
(author)
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Association of neighbourhood socioeconomic status and individual socioeconomic status with cardiovascular risk factors in an Eastern German population : the CARLA Study 2002–2006
- 2011
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In: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland Programme and abstracts. - : BMJ. ; , s. A249-
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Conference paper (peer-reviewed)abstract
- Introduction/objectives: Individual socioeconomic status (SES) is a determinant of cardiovascular risk factors (RF). Recent studies suggest an independent association of neighbourhood SES with cardiovascular RF, but the mechanisms have not fully been understood. Our aim was to assess the association of neighbourhood and individual SES with cardiovascular RF in an Eastern German population. Methods: We used cross-sectional data of 1779 participants aged 45–83 years of the population-based CARLA study. We calculated linear mixed models to assess the age-adjusted influence of neighbourhood-specific unemployment rates and individual SES on smoking, systolic blood pressure (SBP), and body mass index (BMI). Spatial dependencies within and between neighbourhoods were adjusted for by using ICAR models. Results: Neighbourhood-specific unemployment rates varied between 6.3 and 35.3%. Per 1% increase in the neighbourhood's unemployment rate, the number of cigarettes smoked/day increased by 0.11 in men (95% CI 0.09 to 0.12) and 0.05, (CI 0.04 to 0.07) in women. In women, SBP increased by 0.04 mm Hg with unemployment rate (CI 0.03 to 0.06), while there was no statistically significant association of SBP with SES in men. BMI was only in women significantly associated with unemployment (increase in BMI per 1% increase in unemployment rate 0.04 (CI 0.02 to 0.05)). Associations of RF with individual SES were stronger than with neighbourhood SES in multiple models. Conclusions: Our findings confirm the previously described association of neighbourhood SES with smoking independent of individual SES, while we found inconsistent associations with SBP and BMI. The neighbourhood environment may be more relevant for behavioural than for biomedical risk factors.
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- Schumann, Barbara, et al.
(author)
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Association of occupation with prevalent hypertension in an elderly East German population : an exploratory cross-sectional analysis
- 2011
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In: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 0340-0131 .- 1432-1246. ; 84, s. 361-369
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Journal article (peer-reviewed)abstract
- Purpose Hypertension is one of the most relevant risk factors for cardiovascular disease; however, little is known about differences in hypertension by occupation. The aim of this study was to explore the association between occupational group and prevalent hypertension. Methods Cross-sectional data of the CARLA study were used, a representative sample of an East German population aged 45–83. Job titles of the current or last held occupation of 967 men and 808 women were coded using the German classification of occupation. Hypertension was defined as blood pressure of ≥140 mmHg (systolic), ≥90 mmHg (diastolic) or use of antihypertensives. Sex-stratified, age-adjusted prevalence risk ratios (PR) with 95% confidence intervals (CI) were calculated for 31 occupational groups. Results Hypertension was prevalent in 79% of the population. In men, highest age-adjusted prevalence ratios were observed in metal-processing workers, carpenters/painters, and electricians with PRs of 1.31 (CI 1.04–1.65), 1.28 (CI 1.00–1.64), and 1.21 (0.95–1.53), respectively, compared to office clerks. In women, highest PRs were found in technicians/forewomen, scrutinisers/storekeepers, and food-processing occupations with PR 1.28 (1.09–1.49), 1.23 (0.99–1.51), and 1.22 (1.01–1.48), respectively. Adjustment for education, smoking, body mass index, and current work hours did not fully explain occupational differences. Excluding currently non-working subjects lead to decreased PRs in men and to increased PR in women. Conclusions Differences in the prevalences of hypertension by occupational group were only partly explained by conventional risk factors and may require workplace interventions targeted at high-risk occupations. Longitudinal data with large cohorts and work-related exposure assessment are needed to confirm a temporal relationship between occupation and incident hypertension.
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