Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study...

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10^-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression r_g = 0.63, insomnia r_g = 0.47), physical health (overweight r_g = 0.19, waist-to-hip ratio r_g = 0.32), smoking (r_g = 0.54), cognitive ability (intelligence r_g = -0.40), educational attainment (years of schooling r_g = -0.46) and reproductive traits (age at first birth r_g = -0.58, father's age at death r_g = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.