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

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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 formeta-analysis from March 1, 2014, toMay 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
Issue number12
StatePublished - Dec 2017

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© 2017 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Psychiatry and Mental health


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