Widespread covariation of early environmental exposures and trait-associated polygenic variation.

ABSTRACT

Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R2 = 0.008; P = 5e-13), parental smacking (R2 = 0.01; P = 4e-15), household income (R2 = 0.032; P = 1e-22), watching television (R2 = 0.034; P = 5e-47), and maternal education (R2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.