TY - JOUR
T1 - Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
AU - COGA Consortium
AU - Spit for Science Working Group
AU - Tielbeek, Jorim J.
AU - Uffelmann, Emil
AU - Williams, Benjamin S.
AU - Colodro-Conde, Lucía
AU - Gagnon, Éloi
AU - Mallard, Travis T.
AU - Levitt, Brandt E.
AU - Jansen, Philip R.
AU - Johansson, Ada
AU - Sallis, Hannah M.
AU - Pistis, Giorgio
AU - Saunders, Gretchen R.B.
AU - Allegrini, Andrea G.
AU - Rimfeld, Kaili
AU - Konte, Bettina
AU - Klein, Marieke
AU - Hartmann, Annette M.
AU - Salvatore, Jessica E.
AU - Nolte, Ilja M.
AU - Demontis, Ditte
AU - Malmberg, Anni L.K.
AU - Burt, S. Alexandra
AU - Savage, Jeanne E.
AU - Sugden, Karen
AU - Poulton, Richie
AU - Harris, Kathleen Mullan
AU - Vrieze, Scott
AU - McGue, Matt
AU - Iacono, William G.
AU - Mota, Nina Roth
AU - Mill, Jonathan
AU - Viana, Joana F.
AU - Mitchell, Brittany L.
AU - Morosoli, Jose J.
AU - Andlauer, Till F.M.
AU - Ouellet-Morin, Isabelle
AU - Tremblay, Richard E.
AU - Côté, Sylvana M.
AU - Gouin, Jean Philippe
AU - Brendgen, Mara R.
AU - Dionne, Ginette
AU - Vitaro, Frank
AU - Lupton, Michelle K.
AU - Martin, Nicholas G.
AU - Porjesz, Bernice
AU - Hesselbrock, Victor
AU - Foroud, Tatiana
AU - Agrawal, Arpana
AU - Goate, Alison
AU - Slesinger, Paul
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/11
Y1 - 2022/11
N2 - 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 × 10−10). 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.
AB - 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 × 10−10). 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.
UR - http://www.scopus.com/inward/record.url?scp=85141068730&partnerID=8YFLogxK
U2 - 10.1038/s41380-022-01793-3
DO - 10.1038/s41380-022-01793-3
M3 - Article
C2 - 36284158
AN - SCOPUS:85141068730
SN - 1359-4184
VL - 27
SP - 4453
EP - 4463
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 11
ER -