Gene–Environment Interplay Beyond Interactions: Psychosocial Environments Mediate Genetic Effects Underlying Externalizing-Behavior Trajectories

Studies of gene-environment interplay largely focus on just one form of interplay–interaction–while neglecting the possibility of mediation, where genetic effects may operate indirectly through psychosocial environments. In this study, we used data from the National Longitudinal Study of Adolescent to Adult Health (N = 20,745) to characterize latent trajectories of substance use (SUB) and antisocial behavior (ASB) from ages 13 to 41 and computed polygenic scores (PGS; N = 4,868) for externalizing behaviors to investigate both interaction and mediation effects for SUB and ASB trajectories. Environmental factors examined were supportive parenting, delinquent peer affiliation, school connectedness, and neighborhood connectedness. Results showed no evidence of interaction effects. The association of PGS with SUB and ASB trajectories operated indirectly through psychosocial environments, most prominently via deviant peer affiliation, which mediated 13.6 - 51.3% of total genetic effects. Findings highlight how the interplay between nature and nurture goes beyond interactions alone.