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dc.contributor.authorWinkler, Thomas W
dc.contributor.authorJustice, Anne E
dc.contributor.authorGraff, Mariaelisa
dc.contributor.authorBarata, Llilda
dc.contributor.authorFeitosa, Mary F
dc.contributor.authorChu, Su
dc.contributor.authorCzajkowski, Jacek
dc.contributor.authorEsko, Tõnu
dc.contributor.authorFall, Tove
dc.contributor.authorYaluri, Alena
dc.date.accessioned2016-06-06T09:08:34Z
dc.date.available2016-06-06T09:08:34Z
dc.date.issued2015-10-01
dc.identifierdoi: 10.1371/journal.pgen.1005378
dc.identifier.citationWinkler TW, Justice AE, Graff M, Barata L, Feitosa MF, Chu S, 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 Genet 11(10): e1005378. doi:10.1371/journal.pgen.1005378
dc.identifier.issn1553-7404
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/41
dc.descriptionArticle
dc.description.abstractGenome-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.
dc.language.isoen
dc.publisherPublic Library of Science (PLoS)
dc.relation.ispartofseries11 (10);
dc.relation.urihttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005378
dc.rightsThis 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.
dc.subjectGenetic loci
dc.subjectGenome-wide association studies
dc.subjectMeta-analysis
dc.subjectBody mass index
dc.subjectAdults
dc.subjectSexual dimorphism
dc.subjectHuman genetics
dc.subjectFats
dc.titleThe Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.rights.licenseLicenced under CC0 1.0 Universal (CC0 1.0) https://creativecommons.org/publicdomain/zero/1.0/
dc.description.versionPublisher's PDF
dc.contributor.departmentTerveystieteiden tiedekunta
uef.solecris.id35485014
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.type.publicationinfo:eu-repo/semantics/article
dc.relation.doidoi: 10.1371/journal.pgen.1005378
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.issn1553-7404


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