Citation

Tielbeek JJ, Uffelmann E, Williams BS, Colodro-Conde L, Gagnon, 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 JP, Brendgen MR, Dionne G, Vitaro F, Lupton MK, Martin NG, 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 JB, Glennon JC, Barnes JC, Fisher SE, Moffitt TE, Caspi A, Polderman TJC, Posthuma D. Mol. Psychiatry 2022; ePub(ePub): ePub.

Copyright

(Copyright © 2022, Nature Publishing Group)

DOI

10.1038/s41380-022-01793-3

PMID

36284158

Abstract

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.

Language: en