TY - JOUR
T1 - The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape
T2 - A Large-Scale Genome-Wide Interaction Study
AU - CHARGE consortium
AU - DIAGRAM Consortium
AU - GLGC Consortium
AU - Global BPgen Consortium
AU - ICBP Consortium
AU - MAGIC Consortium
AU - Winkler, Thomas W.
AU - Justice, Anne E.
AU - Graff, Mariaelisa
AU - Barata, Llilda
AU - Feitosa, Mary F.
AU - Chu, Su
AU - Czajkowski, Jacek
AU - Esko, Tõnu
AU - Fall, Tove
AU - Kilpeläinen, Tuomas O.
AU - Lu, Yingchang
AU - Mägi, Reedik
AU - Mihailov, Evelin
AU - Pers, Tune H.
AU - Rüeger, Sina
AU - Teumer, Alexander
AU - Ehret, Georg B.
AU - Ferreira, Teresa
AU - Heard-Costa, Nancy L.
AU - Karjalainen, Juha
AU - Lagou, Vasiliki
AU - Mahajan, Anubha
AU - Neinast, Michael D.
AU - Prokopenko, Inga
AU - Simino, Jeannette
AU - Teslovich, Tanya M.
AU - Jansen, Rick
AU - Westra, Harm Jan
AU - White, Charles C.
AU - Absher, Devin
AU - Ahluwalia, Tarunveer S.
AU - Ahmad, Shafqat
AU - Albrecht, Eva
AU - Alves, Alexessander Couto
AU - Bragg-Gresham, Jennifer L.
AU - de Craen, Anton J.M.
AU - Bis, Joshua C.
AU - Bonnefond, Amélie
AU - Boucher, Gabrielle
AU - Cadby, Gemma
AU - Cheng, Yu Ching
AU - Chiang, Charleston W.K.
AU - Delgado, Graciela
AU - Demirkan, Ayse
AU - Dueker, Nicole
AU - Eklund, Niina
AU - Eiriksdottir, Gudny
AU - Eriksson, Joel
AU - Feenstra, Bjarke
AU - Hottenga, Jouke Jan
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84961711372
U2 - 10.1371/journal.pgen.1005378
DO - 10.1371/journal.pgen.1005378
M3 - Article
C2 - 26426971
AN - SCOPUS:84961711372
SN - 1553-7390
VL - 11
SP - 1
EP - 42
JO - PLoS Genetics
JF - PLoS Genetics
IS - 10
M1 - e1005378
ER -