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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.authorKilpeläinen, Tuomas O.
dc.contributor.authorLu, Yingchang
dc.contributor.authorMägi, Reedik
dc.contributor.authorMihailov, Evelin
dc.contributor.authorPers, Tune H.
dc.contributor.authorRüeger, Sina
dc.contributor.authorTeumer, Alexander
dc.contributor.authorEhret, Georg B.
dc.contributor.authorFerreira, Teresa
dc.contributor.authorHeard-Costa, Nancy L.
dc.contributor.authorKarjalainen, Juha
dc.contributor.authorLagou, Vasiliki
dc.contributor.authorMahajan, Anubha
dc.contributor.authorNeinast, Michael D.
dc.contributor.authorProkopenko, Inga
dc.contributor.authorSimino, Jeannette
dc.contributor.authorTeslovich, Tanya M.
dc.contributor.authorJansen, Rick
dc.contributor.authorWestra, Harm-Jan
dc.contributor.authorWhite, Charles C.
dc.contributor.authorAbsher, Devin
dc.contributor.authorAhluwalia, Tarunveer S.
dc.contributor.authorAhmad, Shafqat
dc.contributor.authorAlbrecht, Eva
dc.contributor.authorAlves, Alexessander Couto
dc.contributor.authorBragg-Gresham, Jennifer L.
dc.contributor.authorde Craen, Anton J. M.
dc.contributor.authorBis, Joshua C.
dc.contributor.authorBonnefond, Amélie
dc.contributor.authorCadby, Gemma
dc.contributor.authorCheng, Yu-Ching
dc.contributor.authorChiang, Charleston W. K.
dc.contributor.authorDelgado, Graciela
dc.contributor.authorDemirkan, Ayse
dc.contributor.authorDueker, Nicole
dc.contributor.authorEklund, Niina
dc.contributor.authorEiriksdottir, Gudny
dc.contributor.authorHolmen, Oddgeir
dc.contributor.authorHveem, Kristian
dc.contributor.authorNjølstad, Inger
dc.date.accessioned2016-03-03T13:23:00Z
dc.date.available2016-03-03T13:23:00Z
dc.date.issued2015-10-01
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.en_US
dc.description.abstractAdult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.en_US
dc.identifier.citationPLoS Genetics 2015, 11(10)en_US
dc.identifier.issn1553-7404
dc.identifier.otherFRIDAID 1313928
dc.identifier.other10.1371/journal.pgen.1005378
dc.identifier.urihttps://hdl.handle.net/10037/8654
dc.identifier.urnURN:NBN:no-uit_munin_8234
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801en_US
dc.titleThe Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Studyen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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