title: Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior.
abstract: Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Child and Adolescent Psychiatry, VU University Medical Center Amsterdam, Duivendrecht, The Netherlands.|Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jorim J
authors.initials: JJ
authors.lastname: Tielbeek
authors.affiliation: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Karlsson Linnér
authors.affiliation: Department of Child and Adolescent Psychiatry, VU University Medical Center Amsterdam, Duivendrecht, The Netherlands.|Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Koko
authors.initials: K
authors.lastname: Beers
authors.affiliation: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam, Amsterdam, The Netherlands.|Section Complex Trait Genetics, Department of Clinical Genetics, Neuroscience Campus Amsterdam (NCA), VU University Medical Centre Amsterdam, Amsterdam, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Posthuma
authors.affiliation: Department of Child and Adolescent Psychiatry, VU University Medical Center Amsterdam, Duivendrecht, The Netherlands.|Faculty of Law, Institute of Criminal Law and Criminology, Leiden University, Leiden, The Netherlands.
authors.forename: Arne
authors.initials: A
authors.lastname: Popma
authors.affiliation: Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tinca J C
authors.initials: TJ
authors.lastname: Polderman
mesh_terms: D000374:Aggression / Q000502:physiology* / Q000523:psychology; D000483:Alleles; D000987:Antisocial Personality Disorder / Q000235:genetics*; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012919:Social Behavior
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: adverse childhood environment (ACE); criminology; genetics; maltreatment; review