The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

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 320485 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