A1 Refereed original research article in a scientific journal

Genome-wide association studies of a broad spectrum of antisocial behavior




AuthorsTielbeek JJ, Johansson A, Polderman TJC, Rautiainen MR, 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, Munafo 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

PublisherAMER MEDICAL ASSOC

Publication year2017

JournalJAMA Psychiatry

Journal name in sourceJAMA PSYCHIATRY

Journal acronymJAMA PSYCHIAT

Volume74

Issue12

First page 1242

Last page1250

Number of pages9

ISSN2168-622X

eISSN2168-6238

DOIhttps://doi.org/10.1001/jamapsychiatry.2017.3069

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/28726726


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) (R-2 = 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.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.





Last updated on 2024-26-11 at 23:27