Which genetic variants are associated with antisocial behavior, are they sex specific, and do they correlate with other traits?
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.
Larger samples, divided by sex, are needed to validly identify genetic variants associated with antisocial behavior.
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.
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.
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.
Tielbeek JJ, Johansson A, Polderman TJC, Rautiainen M, Jansen P, Taylor M, Tong X, Lu Q, Burt AS, Tiemeier H, Viding E, Plomin R, Martin NG, Heath AC, Madden PAF, Montgomery G, Beaver KM, Waldman I, Gelernter J, Kranzler HR, Farrer LA, Perry JRB, Munafò M, LoParo D, Paunio T, Tiihonen J, Mous SE, Pappa I, de Leeuw C, Watanabe K, Hammerschlag AR, Salvatore JE, Aliev F, Bigdeli TB, Dick D, Faraone SV, Popma A, Medland SE, Posthuma D, for the Broad Antisocial Behavior Consortium collaborators. Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior. JAMA Psychiatry. Published online October 04, 2017. doi:10.1001/jamapsychiatry.2017.3069
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