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

Abstract

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 five large datasets to characterize behavioral manifestations of a genetic liability toward externalizing from ages 6 months- 26 years. METHOD We used polygenic scores (PGS) derived from a multivariate GWAS of Externalizing that identified hundreds of significantly associated genetic variants (EXTPGS) to estimate associations of genetic liability with relevant phenotypes within and across developmental periods, ranging from toddlerhood to early adulthood. We used data from five population- and family-based datasets spanning three countries. RESULTS The EXTPGS was significantly associated with a breadth of externalizing phenotypes from toddlerhood to early adulthood. Higher EXTPGS was consistently associated with measures of impulsivity from early adolescence to early adulthood. Individuals with higher EXTPGS were more likely to experience conduct problems and symptoms of oppositional defiant and attention-deficit/hyperactivity disorders. Further, the EXTPGS was associated with higher levels of substance use and problems beginning in early adolescence through early adulthood, including alcohol and other 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.