Gene–environment correlations across geographic regions affect genome-wide association studies

Gene-environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene-environment correlations, and that migration extends these gene-environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals. Controlling for geographic regions significantly decreased the heritability for socioeconomic status (SES)-related traits, most strongly for educational attainment and income. For most traits, controlling for regions significantly reduced genetic correlations with educational attainment and income, most significantly for body mass index/body fat, sedentary behavior and substance use, consistent with gene-environment correlations related to regional socio-economic differences. The effects of controlling for birthplace and current address suggest both passive and active sources of gene-environment correlations. Our results show that the geographic clustering of DNA and SES introduces gene-environment correlations that affect GWAS results.