The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
Journal article
Winkler, T.W., Justice, A.E., Graff, M., Barata, Llilda, Feitosa, M.F., Chu, Su, Czajkowski, Jacek, Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Yingchang, Mägi, R., Mihailov, E., Lorentzon, Karl Mattias, Vandenput, Liesbeth and et. al.. (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), pp. 1-42. https://doi.org/10.1371/journal.pgen.1005378
Authors | Winkler, T.W., Justice, A.E., Graff, M., Barata, Llilda, Feitosa, M.F., Chu, Su, Czajkowski, Jacek, Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Yingchang, Mägi, R., Mihailov, E., Lorentzon, Karl Mattias, Vandenput, Liesbeth and et. al. |
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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 | Genetic loci; Single nucleotide polymorphisms; Genome-wide association studies; Metaanalysis; Body mass index; Human genetics; Body weight; Sexual dimorphism |
Year | 01 Jan 2015 |
Journal | PLoS Genetics |
Journal citation | 11 (10), pp. 1-42 |
Publisher | Public Library of Science |
ISSN | 1553-7390 |
Digital Object Identifier (DOI) | https://doi.org/10.1371/journal.pgen.1005378 |
Web address (URL) | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005378 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-42 |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
01 Oct 2015 | |
Publication process dates | |
Accepted | 22 Jun 2015 |
Deposited | 20 May 2024 |
Additional information | 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. |
The stratified genome-wide association meta-analysis results for BMI and waist-hip ratio are available from the GIANT Consortium website www.broadinstitute.org/collaboration/giant | |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/90882/the-influence-of-age-and-sex-on-genetic-associations-with-adult-body-size-and-shape-a-large-scale-genome-wide-interaction-study
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Publisher's version
OA_Lorentzon_2015_The_influence_of_age_and_sex.pdf | |
License: CC0 | |
File access level: Open |
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