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

Jorim J Tielbeek, Ada Johansson, Tinca J C Polderman, Marja-Riitta Rautiainen, Philip Jansen, Michelle Taylor, Xiaoran Tong, Qing Lu, Alexandra S Burt, Henning Tiemeier, Essi Viding, Robert Plomin, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Grant Montgomery, Kevin M Beaver, Irwin Waldman, Joel Gelernter, Henry R KranzlerLindsay A Farrer, John R B Perry, Marcus Munafò, Devon LoParo, Tiina Paunio, Jari Tiihonen, Sabine E Mous, Irene Pappa, Christiaan de Leeuw, Kyoko Watanabe, Anke R Hammerschlag, Jessica E Salvatore, Fazil Aliev, Tim B Bigdeli, Danielle Dick, Stephen V Faraone, Arne Popma, Sarah E Medland, Danielle Posthuma, Broad Antisocial Behavior Consortium collaborators

Research output: Contribution to JournalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1242-1250
Number of pages9
JournalJAMA Psychiatry
Volume74
Issue number12
Early online date4 Oct 2017
DOIs
Publication statusPublished - Dec 2017

Funding

Additional Contributions: Meta-analyses and statistical analyses for the Twins Early Development Study were performed on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by grant NWO 480-05-003 from the Netherlands Organization for Scientific Research. Dr Mous was funded by National Health and Medical Research Council Senior Research Fellowship APP1103623. Gabriel Cellular Partida, PhD, University of Queensland Diamantina Institute, Translational Research Institute, University of Queensland, Brisbane, Queensland, Australia, provided the script for the Miami plot; J.C. Barnes, PhD, School of Criminal Justice, University of Cincinnati, Cincinnati, Ohio, and Philipp Koellinger, PhD, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands, provided helpful comments on the manuscript; and Richard Karlsson Linnér, MSc, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands, provided advice on statistical power. None of these individuals were compensated for their work. This research was facilitated by the Social Science Genetic Association Consortium. We thank the individuals who participated in the studies. A full list of cohort acknowledgments is provided in the Supplement. Funding/Support: This project was funded by grants 406-12-131 and 453-14-005 from the Netherlands Organization for Scientific Research, award K01DA033346 from the National Institute on Drug Abuse, an F32AA022269 fellowship, grant K01AA024152 from the National Institutes of Health, the Foundation “De Drie Lichten” in the Netherlands, the Waldemar von Frenckell Foundation, the Finnish Cultural Foundation, the Finnish Ministry of Health and Social Affairs through the development fund for Niuvanniemi Hospital, Kuopio, Finland, and the Society of Swedish Literature in Finland.

FundersFunder number
National Institutes of Health
National Institute on Drug AbuseF32AA022269, R01DA043501, K01AA024152, K01DA033346
National Health and Medical Research CouncilAPP1103623
Suomen Kulttuurirahasto
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Sosiaali- ja Terveysministeriö
Svenska Litteratursällskapet i Finland
Waldemar von Frenckells Stiftelse

    Keywords

    • Adolescent
    • Adult
    • Antisocial Personality Disorder
    • Child
    • Conduct Disorder
    • Environment
    • Female
    • Finland
    • Genetic Variation
    • Genome-Wide Association Study
    • Humans
    • Journal Article
    • Male
    • Middle Aged
    • Multifactorial Inheritance
    • Sex Factors

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