Characterizing behavioral manifestations of a genetic liability towards self-regulation deficits across development
Creators: name: Choi, Maia
Publisher: name: No Publisher Supplied
Year: 2023

description: Introduction: Behaviors and disorders such as ADHD, conduct disorder, and substance use disorders, aggression, risk taking, and sensation seeking are characterized by impulsivity and 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 externalizing polygenic score (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 had three main aims. First, we used this EXT PGS, to estimate associations between genetic risk for externalizing and relevant behavioral phenotypes across developmental periods, ranging from childhood to adulthood. Second, we examined interactions between the EXT PGS and sex in predicting the externalizing phenotypes. Third, we examined the effects of positive parenting in moderating the association between the EXT PGS and externalizing phenotypes in adolescence.Methods: 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 periods: toddlerhood (0-2), 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.Results: Results indicate significant associations between the EXT PGS and the variety of phenotypes from toddlerhood to early adulthood. Significant associations with the EXT PGS began in toddlerhood with temperament (pFDR&lt;.05). From early childhood to early adulthood, the EXT PGS was consistently associated with the hyperactivity and conduct subscales of the Strengths and Difficulties Questionnaire (pFDR&lt;.05). The EXT PGS was significantly associated with ADHD, ODD, and CD at all timepoints from middle childhood to late adolescence (pFDR&lt;.05) such that individuals with higher EXT PGS also reported higher symptom endorsement for the disorders. There was no evidence for sex interactions with the EXT PGS (pFDR&gt;.05). Parenting practices significantly buffered the association between the EXT PGS and delinquency in early adolescence (pFDR&lt;.05).Conclusion: Overall, findings show wide ranging manifestations of genetic risk for self- regulation deficits across a variety of developmental periods. 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.