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Quantification of the overall contribution of gene-environment interaction for obesity-related traits

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  • Jonathan Sulc

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics)

  • Ninon Mounier

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics)

  • Felix Günther

    (University of Regensburg)

  • Thomas Winkler

    (University of Regensburg)

  • Andrew R. Wood

    (University of Exeter Medical School, University of Exeter)

  • Timothy M. Frayling

    (University of Exeter Medical School, University of Exeter)

  • Iris M. Heid

    (University of Regensburg)

  • Matthew R. Robinson

    (University of Lausanne)

  • Zoltán Kutalik

    (University Center for Primary Care and Public Health, University of Lausanne
    Swiss Institute of Bioinformatics
    University of Exeter Medical School, University of Exeter)

Abstract

The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).

Suggested Citation

  • Jonathan Sulc & Ninon Mounier & Felix Günther & Thomas Winkler & Andrew R. Wood & Timothy M. Frayling & Iris M. Heid & Matthew R. Robinson & Zoltán Kutalik, 2020. "Quantification of the overall contribution of gene-environment interaction for obesity-related traits," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15107-0
    DOI: 10.1038/s41467-020-15107-0
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