Characterizing behavioral manifestations of a genetic liability towards self-regulation deficits across development

Behaviors and disorders such as ADHD, conduct disorder, and substance use disorders, aggression, risk taking, and sensation seeking are characterized by self-regulation deficits. These behaviors and disorders are highly correlated and are often referred to as externalizing phenotypes. A large study led by the externalizing consortium used data from ∼1.5 million individuals to identify genes involved in externalizing. The multivariate externalizing factor was derived from summary statistics from seven individual GWAS on ADHD, problematic alcohol use, cannabis initiation, age at first sex, number of lifetime sexual partners, general risk tolerance, and tobacco initiation. The externalizing (EXT) PGS accounted for nearly 10% of the variance in phenotypic externalizing and is also associated with mental health, behavioral, and social outcomes in independent samples, making it one of the most robust genetic predictors of behavior. In this current project, we used this EXT PGS, to estimate associations between genetic risk for self-regulation deficits and externalizing phenotypes across developmental periods, ranging from early childhood to early adulthood. Data came from The Avon Longitudinal Study of Parents and Children (ALSPAC), which is a large scale, longitudinal cohort study started in 1990 in the United Kingdom. Analyses for this project focused on the offspring with available genotypic data (n=8,013). Externalizing phenotypes studied include temperament, behavioral traits, emotional and behavioral difficulties, antisocial behavior, psychiatric disorders, and substance use. Analyses were divided into developmental epochs: early childhood (3-5 years), middle childhood (6-8 years) late childhood (9-11 years), early adolescence (12-14 years), late adolescence (15-17 years), emerging adulthood (18-21), early adulthood (22-26). For each developmental stage, regression analyses were performed wherein each externalizing phenotype was regressed on the EXT PGS and relevant covariates. For repeated measures within the same developmental period, the maximum score of the measure was used as the phenotype. Results indicate significant associations between the EXT PGS and the variety of phenotypes from early childhood to early adulthood. From early childhood to early adulthood, the EXT PGS was significantly, positively associated with the hyperactivity and conduct subscales of the Strengths and Difficulties Questionnaire (β 0.11-0.21, all p < .0005). The EXT PGS was significantly associated with ADHD, ODD, and CD at all timepoints from middle childhood to late adolescence (β 0.05-0.81, all p < .0005) such that individuals with higher EXT PGS also reported higher symptom endorsement for the disorders. Further, the EXT PGS was significantly associated with the AUDIT alcohol consumption and problem subscales from late adolescence to early adulthood (β 0.16-0.43, all p < .0005) such that higher EXT PGS was associated with higher alcohol consumption and problems. Overall, findings show wide ranging manifestations of genetic risk for self-regulation deficits across a variety of developmental epochs. Results from this study will inform our understanding of the ways in which genetic risk for externalizing is associated with various phenotypes across developmental periods.