title: Antisocial behavior and polymorphisms in the oxytocin receptor gene: findings in two independent samples.
abstract: 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 (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. 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=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Hovey
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Lindstedt
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Zettergren
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Jonsson
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Behavioral Sciences and Philosophy, University of Turku, Turku, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Melke
authors.affiliation: Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Mölndal, Sweden.|R&D Unit, Swedish Prison and Probation Service, Gothenburg, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Kerekes
authors.affiliation: Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Mölndal, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Anckarsäter
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.identifier: 0000-0003-3037-5287
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Mölndal, Sweden.|R&D Unit, Swedish Prison and Probation Service, Gothenburg, Sweden.|Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Lundström
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Westberg
mesh_terms: D000293:Adolescent; D000374:Aggression / Q000502:physiology; D000483:Alleles; D000987:Antisocial Personality Disorder / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism; D012919:Social Behavior; D013548:Sweden; D014427:Twins
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin