Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

dc.contributor.authorTielbeek, Jorim J.
dc.contributor.authorUffelmann, Emil
dc.contributor.authorWilliams, Benjamin S.
dc.contributor.authorColodro-Conde, Lucía
dc.contributor.authorGagnon, Éloi
dc.contributor.authorMallard, Travis T.
dc.contributor.authorLevitt, Brandt E.
dc.contributor.authorJansen, Philip R.
dc.contributor.authorJohansson, Ada
dc.contributor.authorSallis, Hannah M.
dc.contributor.authorPistis, Giorgio
dc.contributor.authorSaunders, Gretchen R. B.
dc.contributor.authorAllegrini, Andrea G.
dc.contributor.authorRimfeld, Kaili
dc.contributor.authorKonte, Bettina
dc.contributor.authorKlein, Marieke
dc.contributor.authorHartmann, Annette M.
dc.contributor.authorSalvatore, Jessica E.
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorDemontis, Ditte
dc.contributor.authorMalmberg, Anni L. K.
dc.contributor.authorBurt, S. Alexandra
dc.contributor.authorSavage, Jeanne E.
dc.contributor.authorSugden, Karen
dc.contributor.authorPoulton, Richie
dc.contributor.authorMullan Harris, Kathleen
dc.contributor.authorVrieze, Scott
dc.contributor.authorMcGue, Matt
dc.contributor.authorIacono, William G.
dc.contributor.authorRoth Mota, Nina
dc.contributor.authorMill, Jonathan
dc.contributor.authorViana, Joana F.
dc.contributor.authorMitchell, Brittany L.
dc.contributor.authorMorosoli, Jose J.
dc.contributor.authorAndlauer, Till F. M.
dc.contributor.authorOuellet-Morin, Isabelle
dc.contributor.authorTremblay, Richard E.
dc.contributor.authorCôté, Sylvana M.
dc.contributor.authorGouin, Jean-Philippe
dc.contributor.authorBrendgen, Mara R.
dc.contributor.authorDionne, Ginette
dc.contributor.authorVitaro, Frank
dc.contributor.authorLupton, Michelle K.
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorCOGA Consortium
dc.contributor.authorSpit for Science Working Group
dc.contributor.authorCastelao, Enrique
dc.contributor.authorRäikkönen, Katri
dc.contributor.authorEriksson, Johan G.
dc.contributor.authorLahti, Jari
dc.contributor.authorHartman, Catharina A.
dc.contributor.authorOldehinkel, Albertine J.
dc.contributor.authorSnieder, Harold
dc.contributor.authorLiu, Hexuan
dc.contributor.authorPreisig, Martin
dc.contributor.authorWhipp, Alyce
dc.contributor.authorVuoksimaa, Eero
dc.contributor.authorLu, Yi
dc.contributor.authorJern, Patrick
dc.contributor.authorRujescu, Dan
dc.contributor.authorGiegling, Ina
dc.contributor.authorPalviainen, Teemu
dc.contributor.authorKaprio, Jaakko
dc.contributor.authorHarden, Kathryn Paige
dc.contributor.authorMunafò, Marcus R.
dc.contributor.authorMorneau-Vaillancourt, Geneviève
dc.contributor.authorPlomin, Robert
dc.contributor.authorViding, Essi
dc.contributor.authorBoutwell, Brian B.
dc.contributor.authorAliev, Fazil
dc.contributor.authorDick, Danielle M.
dc.contributor.authorPopma, Arne
dc.contributor.authorFaraone, Stephen V.
dc.contributor.authorBørglum, Anders D.
dc.contributor.authorMedland, Sarah E.
dc.contributor.authorFranke, Barbara
dc.contributor.authorBoivin, Michel
dc.contributor.authorPingault, Jean-Baptiste
dc.contributor.authorGlennon, Jeffrey C.
dc.contributor.authorBarnes, J. C.
dc.contributor.authorFisher, Simon E.
dc.contributor.authorMoffitt, Terrie E.
dc.contributor.authorCaspi, Avshalom
dc.contributor.authorPolderman, Tinca J. C.
dc.contributor.authorPosthuma, Danielle
dc.contributor.departmentMedical and Molecular Genetics, School of Medicine
dc.date.accessioned2025-03-05T12:28:15Z
dc.date.available2025-03-05T12:28:15Z
dc.date.issued2022
dc.description.abstractDespite 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 × 10-10). 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 rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationTielbeek JJ, Uffelmann E, Williams BS, et al. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis. Mol Psychiatry. 2022;27(11):4453-4463. doi:10.1038/s41380-022-01793-3
dc.identifier.urihttps://hdl.handle.net/1805/46213
dc.language.isoen_US
dc.publisherSpringer Nature
dc.relation.isversionof10.1038/s41380-022-01793-3
dc.relation.journalMolecular Psychiatry
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAggression
dc.subjectAntisocial personality disorder
dc.subjectConduct disorder
dc.subjectMembrane proteins
dc.subjectMultifactorial inheritance
dc.subjectNerve tissue proteins
dc.titleUncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
dc.typeArticle
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