Abstract
Importance: The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin may modulate interpersonal aggression.
Objective: To investigate whether single nucleotide polymorphisms in the oxytocin receptor gene are associated with the expression of antisocial behavior.
Design, setting, and participants: A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study of Sweden (CATSS; n=2,372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1,232) was used for replication. The participants were assessed for antisocial behavior, measured as continuous traits. Eight single nucleotide polymorphisms in the oxytocin receptor gene, selected on previous associations with social and antisocial behavior, were then genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication.
Main outcomes and measures: Participants completed self-assessment questionnaires – Life History of Aggression (available only in CATSS), and Self-Reported Delinquency (available in both samples) – designed to capture antisocial behavior.
Results: In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (p=6.2x10-7 in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded p=2.5x10-5. Furthermore, an association between rs4564970 and Life History of Aggression (p=0.00013) survived correction in the discovery sample, but there was no association with the Self-Reported Delinquency in the replication sample.
Conclusions and relevance: We conclude that the rs7632287 and rs4564970 polymorphisms in the oxytocin receptor gene may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and supports the oxytocin receptor as one potential target in the treatment of aggressive antisocial behavior.
