A Polygenic Risk Score Enhances Risk Prediction for Adolescents' Antisocial Behavior over the Combined Effect of 22 Extra-familial, Familial, and Individual Risk Factors in the Context of the Family Check-Up.

Abstract

Possessing informative tools to predict who is most at risk for antisocial behavior in adolescence is important to help identify families most in need of early intervention. Polygenic risk scores (PRSs) have been shown to predict antisocial behavior, but it remains unclear whether PRSs provide additional benefit above more conventional tools to early risk detection for antisocial behavior. This study examined the utility of a PRS in predicting adolescents' antisocial behavior after accounting for a broad index of children's contextual and individual risk factors for antisocial behavior. Participants were drawn from a longitudinal family-based prevention study (N = 463; Ncontrol = 224; 48.8% girls; 45.1% White; 30.2% Black; 12.7% Hispanic/Latino, 10.4% biracial; 0.2% Native American). Participants were recruited from US-based Women, Infants, and Children Nutritional Supplement programs. A risk tolerance PRS was created from a genome-wide association study. We created a robust measure capturing additive effects of 22 conventional measures of a risk of antisocial behavior assessed at child age 2 (before intervention). A latent variable capturing antisocial behavior (ages 10.5-16) was created. After accounting for intervention status and the conventional risk index, the risk tolerance PRS predicted independent variance in antisocial behavior. A PRS-by-conventional risk interaction showed that the conventional risk measure only predicted antisocial behavior at high levels of the PRS. Thus, the risk tolerance PRS provides unique predictive information above conventional screening tools and, when combined with them, identified a higher-risk subgroup of children. Integrating PRSs could facilitate risk identification and, ultimately, prevention screening, particularly in settings unable to serve all individuals in need.