Associations Between a Genetic Liability Toward Externalizing and Behavioral Outcomes Spanning Toddlerhood Through Early Adulthood in Five Developmental Cohorts

Objective: Understanding how genetic risk unfolds across development will be important for using genetics to inform prevention and early intervention. The current study leverages information from 5 large datasets to characterize behavioral manifestations of a genetic liability toward externalizing from ages 6 months to 26 years. Method: We used polygenic scores (PGS) derived from a multivariate genome-wide association study (GWAS) of externalizing that identified hundreds of significantly associated genetic variants (EXT_PGS) to estimate associations of genetic liability with relevant phenotypes within and across developmental periods, ranging from toddlerhood to early adulthood. We used data from 5 population- and family-based datasets spanning 3 countries. Results: The EXT_PGS was significantly associated with a breadth of externalizing phenotypes from toddlerhood to early adulthood. Higher EXT_PGS was consistently associated with measures of impulsivity from early adolescence to early adulthood. Individuals with higher EXT_PGS were more likely to experience conduct problems and symptoms of oppositional defiant and attention-deficit/hyperactivity disorders. Furthermore, the EXT_PGS was associated with higher levels of substance use and problems beginning in early adolescence through early adulthood, including alcohol and illicit drug use. There was minimal evidence for sex interactions. Conclusion: A genetic liability toward externalizing is associated a wide array of behaviors and psychiatric/substance use outcomes beginning as early as childhood and through emerging adulthood. The early emergence and breadth of behaviors associated with a genetic liability toward externalizing could inform prevention and intervention.