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C. and Abecasis, Goncalo R. and Assimes, Themistocles L. and Barroso, Ines and Berndt, Sonja I. and Boehnke, Michael and Deloukas, Panos and Fox, Caroline S. and Groop, Leif C. and Hunter, David J. and Ingelsson, Erik and Kaplan, Robert C. and McCarthy, Mark I. and Mohlke, Karen L. and O'Connell, Jeffrey R. and Schlessinger, David and Strachan, David P. and Stefansson, Kari and van Duijn, Cornelia M. and Hirschhorn, Joel N. and Lindgren, Cecilia M. and Heid, Iris M. and North, Kari E. and Borecki, Ingrid B. and Kutalik, Zoltan and Loos, Ruth J. F. (2015) The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. PLOS GENETICS, 11 (10): e1005378. ISSN 1553-7404,
Full text not available from this repository. (Request a copy)Abstract
Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SELF-REPORTED HEIGHT; FAT DISTRIBUTION; MASS INDEX; LIFE-COURSE; BIOLOGICAL PATHWAYS; NATURAL MENOPAUSE; PERIPHERAL-BLOOD; WEIGHT-GAIN; COMMON SNPS; LOCI; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Jun 2019 08:18 |
| Last Modified: | 06 Jun 2019 08:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4693 |
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