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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Salo P; Sanna S; Scharnagl H; Shi JX; Smith AV; Southam L; Stancakova A; Steinthorsdottir V; Strawbridge RJ; Sung YJ; Tachmazidou I; Tanaka T; Thorleifsson G; Trompet S; Pervjakova N; Tyrer JP; Vandenput L; van der Laan SW; van der Velde N; van Setten J; van Vliet-Ostaptchouk JV; Verweij N; Vlachopoulou E; Waite LL; Wang SR; Wang ZM; Wild SH; Willenborg C; Wilson JF; Wong A; Yang J; Yengo L; Yerges-Armstrong LM; Yu L; Zhang WH; Zhao JH; Andersson EA; Bakker SJL; Baldassarre D; Banasik K; Barcella M; Barlassina C; Bellis C; Benaglio P; Blangero J; Bluher M; Bonnet F; Bonnycastle LL; Boyd HA; Bruinenberg M; Buchman AS; Campbell H; Chen YDI; Chines PS; Claudi-Boehm S; Cole J; Collins FS; de Geus EJC; de Groot LCPGM; Dimitriou M; Duan J; Enroth S; Eury E; Farmaki AE; Forouhi NG; Friedrich N; Gejman PV; Gigante B; Glorioso N; Go AS; Gottesman O; Grassler J; Grallert H; Grarup N; Gu YM; Broer L; Ham AC; Hansen T; Harris TB; Hartman CA; Hassinen M; Hastie N; Hattersley AT; Heath AC; Henders AK; Hernandez D; Hillege H; Holmen O; Hovingh KG; Hui J; Husemoen LL; Hutri-Kahonen N; Hysi PG; Illig T; De Jager PL; Jalilzadeh S; Jorgensen T; Jukema JW; Juonala M; Kanoni S; Karaleftheri M; Khaw KT; Kinnunen L; Kittner SJ; Koenig W; Kolcic I; Kovacs P; Krarup NT; Kratzer W; Kruger J; Kuh D; Kumari M; Kyriakou T; Langenberg C; Lannfelt L; Lanzani C; Lotay V; Launer LJ; Leander K; Lindstrom J; Linneberg A; Liu YP; Lobbens S; Luben R; Lyssenko V; Mannisto S; Magnusson PK; McArdle WL; Menni C; Merger S; Milani L; Montgomery GW; Morris AP; Narisu N; Nelis M; Ong KK; Palotie A; Perusse L; Pichler I; Pilia MG; Pouta A; Rheinberger M; Ribel-Madsen R; Richards M; Rice KM; Rice TK; Rivolta C; Salomaa V; Sanders AR; Sarzynski MA; Scholtens S; Scott RA; Scott WR; Sebert S; Sengupta S; Sennblad B; Seufferlein T; Silveira A; Slagboom PE; Smit JH; Sparso TH; Stirrups K; Stolk RP; Stringham HM; Swertz MA; Swift AJ; Syvanen AC; Tan ST; Thorand B; Tonjes A; Tremblay A; Tsafantakis E; van der Most PJ; Volker U; 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Hirschhorn JN; Lindgren CM; Heid IM; North KE; Borecki IB; Kutalik Z; Loos RJF
https://urn.fi/URN:NBN:fi-fe2021042715239
Tiivistelmä
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.
Kokoelmat
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