The E Is in the G: Gene–Environment–Trait Correlations and Findings From Genome-Wide Association Studies

Abstract

Genome-wide association studies (GWASs) have shown that pleiotropy is widespread (i.e., the same genetic variants affect multiple traits) and that complex traits are polygenic (i.e., affected by many genetic variants with very small effect sizes). However, despite the growing number of GWASs, the possible contribution of gene–environment correlations (rGEs) to pleiotropy and polygenicity has been mostly ignored. rGEs can lead to environmentally mediated pleiotropy or gene–environment–trait correlations (rGETs), given that an environment that is affected by one genetically influenced phenotype, can in turn affect a different phenotype. By adding correlations with environmentally mediated genetic variants, rGETs can contribute to polygenicity. Socioeconomic status (SES) and the experience of stressful life events may, for example, be involved in rGETs. Both are genetically influenced and have been associated with a myriad of physical and mental disorders. As a result, GWASs of these disorders may find the genetic correlates of SES and stressful life events. Consequently, some of the genetic correlates of physical and mental disorders may be modified by public policy that affects environments such as SES and stressful life events. Thus, identifying rGETs can shed light on findings from GWASs and have important implications for public health.