The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape

A Large-Scale Genome-Wide Interaction Study

CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e1005378
JournalPLoS Genetics
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

body shape
Body Size
anthropometric measurements
body size
genome
Genome
gender
Meta-Analysis
Body Weights and Measures
Waist-Hip Ratio
Genome-Wide Association Study
waist-to-hip ratio
loci
Single Nucleotide Polymorphism
effect
dimorphism
meta-analysis
statistics
Weights and Measures
Biological Sciences

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, & MAGIC Consortium (2015). The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. PLoS Genetics, 11(10), e1005378. https://doi.org/10.1371/journal.pgen.1005378

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study. / CHARGE Consortium; DIAGRAM Consortium; GLGC Consortium; Global-BPGen Consortium; ICBP Consortium; MAGIC Consortium.

In: PLoS Genetics, Vol. 11, No. 10, 01.10.2015, p. e1005378.

Research output: Contribution to journalArticle

CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium & MAGIC Consortium 2015, 'The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study', PLoS Genetics, vol. 11, no. 10, pp. e1005378. https://doi.org/10.1371/journal.pgen.1005378
CHARGE Consortium, DIAGRAM Consortium, GLGC Consortium, Global-BPGen Consortium, ICBP Consortium, MAGIC Consortium. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. PLoS Genetics. 2015 Oct 1;11(10):e1005378. https://doi.org/10.1371/journal.pgen.1005378
CHARGE Consortium ; DIAGRAM Consortium ; GLGC Consortium ; Global-BPGen Consortium ; ICBP Consortium ; MAGIC Consortium. / The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study. In: PLoS Genetics. 2015 ; Vol. 11, No. 10. pp. e1005378.
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AU - ICBP Consortium

AU - MAGIC Consortium

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