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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Rauramaa R; Jorgensen T; Scholtens S; Mahajan A; Gu YM; Boomsma DI; Pervjakova N; Bluher M; Leach IM; Cadby G; Waldenberger M; Musk AW; Renstrom F; Sarzynski MA; Fox CS; Neinast MD; Rotter JI; Hassinen M; van der Velde N; Tuomilehto J; Launer LJ; Liu YP; van Setten J; Tonjes A; Sorensen TIA; Palotie A; Langenberg C; Lindgren CM; Collins FS; Sung YJ; Kuh D; Lettre G; Heliovaara M; Stirrups K; Grarup N; Juonala M; Lahti J; Ferrucci L; Rice KM; Kaplan RC; Moll FL; Laakso M; Husemoen LL; Swift AJ; Tyrer JP; Clegg DJ; Ridker PM; Monda KL; Farmaki AE; Thorand B; Franks PW; Smith AV; Willenborg C; Rao DC; Bergman RN; Sennblad B; Liu YF; Maerz W; Justice AE; Illig T; Dedoussis G; Grassler J; Viikari JS; Koenig W; Bennett DA; Graff M; Jacobs KB; Rayner NW; Wennauer R; Willemsen G; Pedersen NL; Pers TH; Gudnason V; Zeggini E; Kaakinen M; Albrecht E; de Geus EJC; Hirschhorn JN; Rizzi F; Tachmazidou I; Eury E; Hu F; Schwarz PEH; Jalilzadeh S; Gottesman O; Grammer TB; Waite LL; Duan J; Raitakari OT; 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Martin NG; Barroso I; Andersson EA; Chanock SJ; Yang J; Nieminen MS; van der Most PJ
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
- Rinnakkaistallenteet [19207]