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 traitassociated 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 traitassociated 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 (R 2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R 2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R 2 = 0.008; P = 5e-13), parental smacking (R 2 = 0.01; P = 4e-15), household income (R 2 = 0.032; P = 1e-22), watching television (R 2 = 0.034; P = 5e-47), and maternal education (R 2 = 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.environmental risk | polygenic scores | gene-environment correlation | human complex traits | prediction

Using DNA from mothers and children to study parental investment in children's educational attainment

“…We extend this prior work by incorporating children's polygenic scores in our analyses, finding that children's educationassociated genetics shape the parenting they receive. Together with other recent studies (Dobewall et al, 2018;Krapohl et al, 2017;Selzam et al, 2018), these findings provide molecular-genetic evidence for a bidirectional model of parent-child relations, in which parenting is partly a response to children's characteristics (Bell, 1968;Crouter & Booth, 2003;Pardini, 2008;Sameroff, 2010).…”

“…We demonstrate this here for effects of a parents' genetics on children's outcomes, but this observation likely extends beyond parents to everyone who creates environments inhabited by people -family members; individuals residing outside the family context, such as peers and partners (Conley et al, 2016;Domingue et al, 2018); even people a child may be exposed to only indirectly, such as the grandparents who raised a child's parents (Hällsten & Pfeffer, 2017;Kong et al, 2018;Liu, 2018 ). As much as genetic confounding needs to be considered when estimating environmental effects, 'environmental confounding' needs to be taken into account when estimating genetic effects (Krapohl et al, 2017;Young et al, 2018). Third, our findings show that environments are part of the pathway from genotype to phenotype (Kandler & Zapko-Willmes, 2017;Scarr & McCartney, 1983).…”

The new genetics of intelligence

“…Associations between environmental measures and behavioural traits such as intelligence are also mediated in part by genetic differences. Research using GPS is beginning to confirm these twin study findings about the ‘nature of nurture’ by showing, for example, that EA GPS correlate with social mobility64 and capture covariation between environmental exposures and children’s behaviour problems and educational achievement65. GE correlation provides a general model for how genotypes become phenotypes — how children select, modify and create environments correlated with their genetic propensities.…”

Comparison of adopted and non-adopted individuals reveals gene-environment interplay for education in the UK Biobank

“…A developmental approach is helpful here, since gene-environment correlations likely arise early in childhood, when individuals interact closely with their relatives, and there will be complex reciprocal effects spanning through the life course. Researchers have already started to pinpoint genetically-influenced aspects of families that are associated with polygenic scores for education in the child generation (Wertz et al 2018;Wertz et al 2019;Krapohl et al 2017).…”