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Original Investigation
October 4, 2017

Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

Author Affiliations
  • 1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  • 2Department of Child and Adolescent Psychiatry, VU University Medical Center, Amsterdam, the Netherlands
  • 3QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
  • 4Department of Psychology and Speech-Language Pathology, University of Turku, Turku, Finland
  • 5Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • 6Department of Psychology, Faculty of Arts, Psychology, and Theology, Åbo Akademi University, Turku, Finland
  • 7National Institute for Health and Welfare, Helsinki, Finland
  • 8Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio
  • 9Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • 10Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
  • 11Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, England
  • 12Department of Epidemiology and Biostatistics, Michigan State University, East Lansing
  • 13Department of Psychology, Michigan State University, East Lansing
  • 14Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Center–Sophia Children’s Hospital, Rotterdam, the Netherlands
  • 15Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands
  • 16Division of Psychology and Language Sciences, University College London, London, England
  • 17Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri
  • 18College of Criminology and Criminal Justice, Florida State University, Tallahassee
  • 19Center for Social and Humanities Research, King Abdulaziz University, Jeddah, Saudi Arabia
  • 20Psychology Department, Emory University, Atlanta, Georgia
  • 21Department of Psychology and the Virginia Institute for Psychiatric and Behavioural Genetics, Virginia Commonwealth University, Richmond
  • 22Department of African American Studies, Virginia Commonwealth University, Richmond
  • 23Faculty of Business, Karabuk University, Karabuk, Turkey
  • 24Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond
  • 25Department of Psychology, African American Studies, and Human & Molecular Genetics, Virginia Commonwealth University, Richmond
  • 26Department of Psychiatry and Behavioral Sciences, Psychiatric Genetic Epidemiology and Neurobiology Laboratory, SUNY Upstate Medical University, Syracuse, New York
  • 27Department of Neuroscience and Physiology, Psychiatric Genetic Epidemiology and Neurobiology Laboratory, SUNY Upstate Medical University, Syracuse, New York
  • 28Department of Clinical Genetics, Neuroscience Campus Amsterdam, Vrije Universiteit Medical Center, Amsterdam, the Netherlands
  • 29Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
  • 30Veterans Affairs (VA) Connecticut Healthcare Center, New Haven
  • 31Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 32Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania
  • 33Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts
  • 34MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, England
  • 35Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 36Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland
JAMA Psychiatry. Published online October 4, 2017. doi:10.1001/jamapsychiatry.2017.3069
Key Points

Questions  Which genetic variants are associated with antisocial behavior, are they sex specific, and do they correlate with other traits?

Findings  In this study of genome-wide association data from 5 population-based cohorts and 3 target samples, antisocial behavior was associated with polygenic traits, demonstrating pleiotropic genetic associations with educational attainment and distinct genetic effects across sex.

Meaning  Larger samples, divided by sex, are needed to validly identify genetic variants associated with antisocial behavior.

Abstract

Importance  Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified.

Objectives  To estimate the single-nucleotide polymorphism–based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium.

Design, Setting, and Participants  Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals).

Main Outcome and Measures  This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges.

Results  The discovery samples comprised 16 400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2 = 0.0017 in the most optimal model, P = 0.03). Significant inverse genetic correlation of ASB with educational attainment (r = –0.52, P = .005) was detected.

Conclusions and Relevance  The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.

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