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 PGS approaches have rarely accounted for the phenotypic and developmental heterogeneity in EXT outcomes. Additionally, many genetically informed studies of EXT tend to exclude non-European ancestry groups in their analyses, thus limiting the generalizability of previous findings. We used the ancestrally diverse National Longitudinal Study of Adolescent to Adult Health (analytic N=9,974), spanning age 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 (67.0%), while three were identified for SUB: High Use (35.2%), Typical Use (41.7%), and Low (23.0%). EXT PGSs were consistently associated with persistent trajectories for ASB and SUB (High Decline and High Use, respectively), relative to comparison groups. These findings were replicated when conducted with the European only subsample. Results suggest PGSs may be sensitive to developmental typologies of EXT, where PGSs are more strongly predictive of chronicity in addition to (or possibly rather than) absolute severity.