Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10
). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression r
= 0.63, insomnia r
= 0.47), physical health (overweight r
= 0.19, waist-to-hip ratio r
= 0.32), smoking (r
= 0.54), cognitive ability (intelligence r
= -0.40), educational attainment (years of schooling r
= -0.46) and reproductive traits (age at first birth r
= -0.58, father's age at death r
= -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
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- Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
- Jorim J TielbeekEmil UffelmannBenjamin S WilliamsLucía Colodro-CondeÉloi GagnonTravis T MallardBrandt E LevittPhilip R JansenAda JohanssonHannah M SallisGiorgio PistisGretchen R B SaundersAndrea G AllegriniKaili RimfeldBettina KonteMarieke KleinAnnette M HartmannJessica E SalvatoreIlja M NolteDitte DemontisAnni L K MalmbergS Alexandra BurtJeanne E SavageKaren SugdenRichie PoultonKathleen Mullan HarrisScott VriezeMatt McGueWilliam G IaconoNina Roth MotaJonathan MillJoana F VianaBrittany L MitchellJose J MorosoliTill F M AndlauerIsabelle Ouellet-MorinRichard E TremblaySylvana M CôtéJean-Philippe GouinMara R BrendgenGinette DionneFrank VitaroMichelle K LuptonNicholas G MartinEnrique CastelaoKatri RäikkönenJohan G ErikssonJari LahtiCatharina A HartmanAlbertine J OldehinkelHarold SniederHexuan LiuMartin PreisigAlyce WhippEero VuoksimaaYi LuPatrick JernDan RujescuIna GieglingTeemu PalviainenJaakko KaprioKathryn Paige HardenMarcus R MunafòGeneviève Morneau-VaillancourtRobert PlominEssi VidingBrian B BoutwellFazil AlievDanielle M DickArne PopmaStephen V FaraoneAnders D BørglumSarah E MedlandBarbara FrankeMichel BoivinJean-Baptiste PingaultJeffrey C GlennonJ C BarnesSimon E FisherTerrie E MoffittAvshalom CaspiTinca J C PoldermanDanielle PosthumaCOGA Consortium
- Molecular psychiatry, Vol.27(11), pp.4453-4463
- Psychology; Dunedin Multidisciplinary Health and Development Research Unit (DMHDRU)
- Springer Nature
- Department of Health R01 DA050721 / NIDA NIH HHS R34 AA027347 / NIAAA NIH HHS MC_UU_00011/7 / Medical Research Council U10 AA008401 / NIAAA NIH HHS G19/2 / Medical Research Council R25 AA027402 / NIAAA NIH HHS G1002190 / Medical Research Council MR/P005918/1 / Medical Research Council MC_PC_15018 / Medical Research Council
- 01/11/2022
- Copyright © Springer Nature 2022. All rights reserved. This work was first published in Molecular Psychiatry (Springer). The open access link to the subscription article is provided under the Springer Nature SharedIt Content-Sharing Initiative (https://www.springernature.com/gp/researchers/sharedit) making the view-only full-text article freely and legally accessible to anyone for research purposes and private study via the link: https://rdcu.be/d23jo
- English
- Journal article