Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/98661
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Type: Journal article
Title: The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study
Author: Winkler, T.
Justice, A.
Graff, M.
Barata, L.
Feitosa, M.
Chu, S.
Czajkowski, J.
Esko, T.
Fall, T.
Kilpeläinen, T.
Lu, Y.
Mägi, R.
Mihailov, E.
Pers, T.
Rüeger, S.
Teumer, A.
Ehret, G.
Ferreira, T.
Heard-Costa, N.
Karjalainen, J.
et al.
Citation: PLoS Genetics, 2015; 11(10):e1005378-1-e1005378-42
Publisher: Public Library of Science
Issue Date: 2015
ISSN: 1553-7404
1553-7404
Statement of
Responsibility: 
Thomas W. Winkler ... Lyle J Palmer ... CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium ... et al.
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 ~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 provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
Keywords: CHARGE Consortium; DIAGRAM Consortium; GLGC Consortium; Global-BPGen Consortium; ICBP Consortium; MAGIC Consortium
Description: Corrected by Erratum: Correction: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study, in PLoS Genetics,12(6):e1006166. The arcOGEN Consortium should be listed as an author of this article.
Rights: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
RMID: 0030038677
DOI: 10.1371/journal.pgen.1005378
Appears in Collections:Public Health publications

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