Associations of polygenic scores and developmental trajectories of externalizing behaviors.

Polygenic scores (PGSs) have garnered increasing attention in the clinical sciences due to their robust prediction signals for psychopathology, including externalizing (EXT) behaviors. However, studies leveraging PGSs have rarely accounted for the phenotypic and developmental heterogeneity in EXT outcomes. We used the National Longitudinal Study of Adolescent to Adult Health (analytic = 4,416), spanning ages 13 to 41, to examine associations between EXT PGSs and trajectories of antisocial behaviors (ASB) and substance use behaviors (SUB) identified via growth mixture modeling. Four trajectories of ASB were identified: High Decline (3.6% of the sample), Moderate (18.9%), Adolescence-Peaked (10.6%), and Low (67%), while three were identified for SUB: High Use (35.2%), Typical Use (41.7%), and Low Use (23%). EXT PGSs were consistently associated with persistent trajectories of ASB and SUB (High Decline and High Use, respectively), relative to comparison groups. EXT PGSs were also associated with the Low Use trajectory of SUB, relative to the comparison group. Results suggest PGSs may be sensitive to developmental typologies of EXT, where PGSs are more strongly predictive of in addition to (or possibly rather than) absolute severity.