Uncovering the Genetic Architecture of Broad Antisocial Behavior through a Genome-Wide Association Study Meta-analysis

Abstract

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 25 discovery samples (N=85,359) and five independent replication samples (N = 8,058) 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 x 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ mice) from controls (the BALB/cByJ strain). The SNP-based heritability of ASB was 8.4% (s.e.= 1.2%). 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 positive genetic correlations between ASB and depression (rg = 0.63), smoking (rg = 0.54) and insomnia (rg = 0.47) as well as negative correlations with indicators of life history (age at first birth (rg = -0.58), fathers age at death (rg = -0.54)) and years of schooling (rg = -0.46). Our findings provide a starting point towards identifying critical biosocial risk mechanisms for the development of ASB.