TY  - JOUR
PY  - 2022//
TI  - Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
JO  - Molecular psychiatry
A1  - Tielbeek, Jorim J.
A1  - Uffelmann, Emil
A1  - Williams, Benjamin S.
A1  - Colodro-Conde, Lucia
A1  - Gagnon, Éloi
A1  - Mallard, Travis T.
A1  - Levitt, Brandt E.
A1  - Jansen, Philip R.
A1  - Johansson, Ada
A1  - Sallis, Hannah M.
A1  - Pistis, Giorgio
A1  - Saunders, Gretchen R. B.
A1  - Allegrini, Andrea G.
A1  - Rimfeld, Kaili
A1  - Konte, Bettina
A1  - Klein, Marieke
A1  - Hartmann, Annette M.
A1  - Salvatore, Jessica E.
A1  - Nolte, Ilja M.
A1  - Demontis, Ditte
A1  - Malmberg, Anni L. K.
A1  - Burt, S. Alexandra
A1  - Savage, Jeanne E.
A1  - Sugden, Karen
A1  - Poulton, Richie
A1  - Harris, Kathleen Mullan
A1  - Vrieze, Scott
A1  - McGue, Matt
A1  - Iacono, William G.
A1  - Mota, Nina Roth
A1  - Mill, Jonathan
A1  - Viana, Joana F.
A1  - Mitchell, Brittany L.
A1  - Morosoli, José J.
A1  - Andlauer, Till F. M.
A1  - Ouellet-Morin, Isabelle
A1  - Tremblay, Richard E.
A1  - Côté, Sylvana M.
A1  - Gouin, Jean-Philippe
A1  - Brendgen, Mara R.
A1  - Dionne, Ginette
A1  - Vitaro, Frank
A1  - Lupton, Michelle K.
A1  - Martin, Nicholas G.
A1  - Castelao, Enrique
A1  - Räikkönen, Katri
A1  - Eriksson, Johan G.
A1  - Lahti, Jari
A1  - Hartman, Catharina A.
A1  - Oldehinkel, Albertine J.
A1  - Snieder, Harold
A1  - Liu, Hexuan
A1  - Preisig, Martin
A1  - Whipp, Alyce
A1  - Vuoksimaa, Eero
A1  - Lu, Yi
A1  - Jern, Patrick
A1  - Rujescu, Dan
A1  - Giegling, Ina
A1  - Palviainen, Teemu
A1  - Kaprio, Jaakko
A1  - Harden, Kathryn Paige
A1  - Munafò, Marcus R.
A1  - Morneau-Vaillancourt, Genevieve
A1  - Plomin, Robert
A1  - Viding, Essi
A1  - Boutwell, Brian B.
A1  - Aliev, Fazil
A1  - Dick, Danielle M.
A1  - Popma, Arne
A1  - Faraone, Stephen V.
A1  - Børglum, Anders D.
A1  - Medland, Sarah E.
A1  - Franke, Barbara
A1  - Boivin, Michel
A1  - Pingault, Jean-Baptiste
A1  - Glennon, Jeffrey C.
A1  - Barnes, J. C.
A1  - Fisher, Simon E.
A1  - Moffitt, Terrie E.
A1  - Caspi, Avshalom
A1  - Polderman, Tinca J. C.
A1  - Posthuma, Danielle
SP  - ePub
EP  - ePub
VL  - ePub
IS  - ePub
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 r(g) = 0.63, insomnia r(g) = 0.47), physical health (overweight r(g) = 0.19, waist-to-hip ratio r(g) = 0.32), smoking (r(g) = 0.54), cognitive ability (intelligence r(g) = -0.40), educational attainment (years of schooling r(g) = -0.46) and reproductive traits (age at first birth r(g) = -0.58, father's age at death r(g) = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.<p />  <p>Language: en</p>
LA  - en
SN  - 1359-4184
UR  - http://dx.doi.org/10.1038/s41380-022-01793-3
ID  - ref1
ER  -