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

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Serval ID
serval:BIB_661C5766F23D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
UNIL/CHUV
Title
Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.
Journal
Molecular psychiatry
Author(s)
Tielbeek J.J., Uffelmann E., Williams B.S., Colodro-Conde L., Gagnon É., Mallard T.T., Levitt B.E., Jansen P.R., Johansson A., Sallis H.M., Pistis G., Saunders GRB, Allegrini A.G., Rimfeld K., Konte B., Klein M., Hartmann A.M., Salvatore J.E., Nolte I.M., Demontis D., Malmberg ALK, Burt S.A., Savage J.E., Sugden K., Poulton R., Harris K.M., Vrieze S., McGue M., Iacono W.G., Mota N.R., Mill J., Viana J.F., Mitchell B.L., Morosoli J.J., Andlauer TFM, Ouellet-Morin I., Tremblay R.E., Côté S.M., Gouin J.P., Brendgen M.R., Dionne G., Vitaro F., Lupton M.K., Martin N.G., Castelao E., Räikkönen K., Eriksson J.G., Lahti J., Hartman C.A., Oldehinkel A.J., Snieder H., Liu H., Preisig M., Whipp A., Vuoksimaa E., Lu Y., Jern P., Rujescu D., Giegling I., Palviainen T., Kaprio J., Harden K.P., Munafò M.R., Morneau-Vaillancourt G., Plomin R., Viding E., Boutwell B.B., Aliev F., Dick D.M., Popma A., Faraone S.V., Børglum A.D., Medland S.E., Franke B., Boivin M., Pingault J.B., Glennon J.C., Barnes J.C., Fisher S.E., Moffitt T.E., Caspi A., Polderman TJC, Posthuma D.
Working group(s)
COGA Consortium, Spit for Science Working Group
Contributor(s)
Porjesz B., Hesselbrock V., Foroud T., Agrawal A., Edenberg H.J., Liu Y., Plawecki M.H., Kuperman S., Kramer J.R., Meyers J.M., Kamarajan C., Pandey A., Bierut L., Rice J., Bucholz K.K., Schuckit M.A., Tischfield J., Hart R., Almasy L., Goate A., Slesinger P., Scott D.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
11/2022
Peer-reviewed
Oui
Volume
27
Number
11
Pages
4453-4463
Language
english
Notes
Publication types: Meta-Analysis ; Journal Article
Publication Status: ppublish
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 <sup>-10</sup> ). 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 <sub>g</sub> = 0.63, insomnia r <sub>g</sub> = 0.47), physical health (overweight r <sub>g</sub> = 0.19, waist-to-hip ratio r <sub>g</sub> = 0.32), smoking (r <sub>g</sub> = 0.54), cognitive ability (intelligence r <sub>g</sub> = -0.40), educational attainment (years of schooling r <sub>g</sub> = -0.46) and reproductive traits (age at first birth r <sub>g</sub> = -0.58, father's age at death r <sub>g</sub> = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
Keywords
Animals, Mice, Antisocial Personality Disorder/genetics, Genome-Wide Association Study, Conduct Disorder/genetics, Conduct Disorder/psychology, Aggression/psychology, Multifactorial Inheritance/genetics, Membrane Proteins/genetics, Nerve Tissue Proteins/genetics
OAI-PMH
oai:serval.unil.ch:BIB_661C5766F23D
DOI
10.1038/s41380-022-01793-3
Pubmed
36284158
Web of science
000871806500001
Create date
02/11/2022 8:24
Last modification date
28/12/2022 6:52
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