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

Publication ,  Journal Article
Tielbeek, JJ; Uffelmann, E; Williams, BS; Colodro-Conde, L; Gagnon, É; Mallard, TT; Levitt, BE; Jansen, PR; Johansson, A; Sallis, HM; Pistis, G ...
Published in: Molecular psychiatry
November 2022

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.

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Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

November 2022

Volume

27

Issue

11

Start / End Page

4453 / 4463

Related Subject Headings

  • Psychiatry
  • Nerve Tissue Proteins
  • Multifactorial Inheritance
  • Mice
  • Membrane Proteins
  • Genome-Wide Association Study
  • Conduct Disorder
  • Antisocial Personality Disorder
  • Animals
  • Aggression
 

Citation

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Tielbeek, J. J., Uffelmann, E., Williams, B. S., Colodro-Conde, L., Gagnon, É., Mallard, T. T., … Posthuma, D. (2022). Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis. Molecular Psychiatry, 27(11), 4453–4463. https://doi.org/10.1038/s41380-022-01793-3
Tielbeek, Jorim J., Emil Uffelmann, Benjamin S. Williams, Lucía Colodro-Conde, Éloi Gagnon, Travis T. Mallard, Brandt E. Levitt, et al. “Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.Molecular Psychiatry 27, no. 11 (November 2022): 4453–63. https://doi.org/10.1038/s41380-022-01793-3.
Tielbeek JJ, Uffelmann E, Williams BS, Colodro-Conde L, Gagnon É, Mallard TT, et al. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis. Molecular psychiatry. 2022 Nov;27(11):4453–63.
Tielbeek, Jorim J., et al. “Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.Molecular Psychiatry, vol. 27, no. 11, Nov. 2022, pp. 4453–63. Epmc, doi:10.1038/s41380-022-01793-3.
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. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis. Molecular psychiatry. 2022 Nov;27(11):4453–4463.

Published In

Molecular psychiatry

DOI

EISSN

1476-5578

ISSN

1359-4184

Publication Date

November 2022

Volume

27

Issue

11

Start / End Page

4453 / 4463

Related Subject Headings

  • Psychiatry
  • Nerve Tissue Proteins
  • Multifactorial Inheritance
  • Mice
  • Membrane Proteins
  • Genome-Wide Association Study
  • Conduct Disorder
  • Antisocial Personality Disorder
  • Animals
  • Aggression