Associations of externalizing polygenic scores with externalizing disorders among Mexican youth

Abstract

Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations. Participants (N = 1064; age range 12-17 years old; 58.8% female) were adolescents recruited for a general population survey on adolescent mental health in the Mexico City Metropolitan region and were genotyped. Childhood adversity exposure and externalizing disorders, specifically attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder, and substance use disorder, were assessed via the computer-assisted World Mental Health Composite International Diagnostic Interview for adolescents. A greater externalizing PGS was associated with a greater odds of any externalizing disorder (OR = 1.29 [1.12, 1.48]; p < 0.01) and ADHD (OR = 1.40 [1.15, 1.70]; p < 0.01) in the whole sample, and in females in particular. There were no main effects of the externalizing PGS on conduct disorder, oppositional defiant disorder, or substance use disorder, nor did adversity exposure moderate these associations. Our results suggest that greater genetic propensity for externalizing disorders is associated with increased odds of any externalizing disorders and ADHD among Mexican adolescents, furthering our understanding of externalizing disorder manifestation in this population.

Keywords: Adolescence; Attention deficit hyperactivity disorder; Externalizing disorders; Mexican youth; Polygenic scores; Sex differences.