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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tielbeek, JJ; Uffelmann, E; Williams, BS; Colodro-Conde, L; Gagnon, É; Mallard, TT; Levitt, BE; Jansen, PR; Johansson, A; Sallis, HM; Pistis, G; Saunders, GRB; Allegrini, AG; Rimfeld, K; Konte, B; Klein, M; Hartmann, AM; Salvatore, JE; Nolte, IM; Demontis, D; Malmberg, ALK; Burt, SA; Savage, JE; Sugden, K; Poulton, R; Harris, KM; Vrieze, S; McGue, M; Iacono, WG; Mota, NR; Mill, J; Viana, JF; Mitchell, BL; Morosoli, JJ; Andlauer, TFM; Ouellet-Morin, I; Tremblay, RE; Côté, SM; Gouin, J-P; Brendgen, MR; Dionne, G; Vitaro, F; Lupton, MK; Martin, NG; COGA Consortium, ; Spit for Science Working Group, ; Castelao, E; Räikkönen, K; Eriksson, JG; Lahti, J; Hartman, CA; Oldehinkel, AJ; Snieder, H; Liu, H; Preisig, M; Whipp, A; Vuoksimaa, E; Lu, Y; Jern, P; Rujescu, D; Giegling, I; Palviainen, T; Kaprio, J; Harden, KP; Munafò, MR; Morneau-Vaillancourt, G; Plomin, R; Viding, E; Boutwell, BB; Aliev, F; Dick, DM; Popma, A; Faraone, SV; Børglum, AD; Medland, SE; Franke, B; Boivin, M; Pingault, J-B; Glennon, JC; Barnes, JC; Fisher, SE; Moffitt, TE; Caspi, A; Polderman, TJC; Posthuma, D

Published Date

  • November 2022

Published In

Volume / Issue

  • 27 / 11

Start / End Page

  • 4453 - 4463

PubMed ID

  • 36284158

Electronic International Standard Serial Number (EISSN)

  • 1476-5578

International Standard Serial Number (ISSN)

  • 1359-4184

Digital Object Identifier (DOI)

  • 10.1038/s41380-022-01793-3


  • eng