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

Jorim Tielbeek*, Emil Uffelmann, Benjamin Williams, Lucia Colodro-Conde, Eloi Gagnon, Travis Mallard, Brandt Levitt, Philip Jansen, Ada Johansson, Hannah Sallis, Giorgio Pistis, Gretschen Saunders, Andrea Allegrini, Kaili Rimfeld, Bettina Konte, Marieke Klein, Annette Hartmann, Jessica Salvatore, Ilja Nolte, Ditte DemontisAnni Malmberg, Alexandra Burt, Jeanne Savage, Karen Sugden, Richie Poulton, Kathleen Mullan Harris, Scott Vrieze, Matt McGue, William Iacono, Nina Roth Mota, Jonathan Mill, Joana Viana, Brittany Mitchell, Jose Morosoli, Till Andlauer, Isabelle Ouellet-Morin, Richard Tremblay, Sylvana Côté, Jean-Philippe Gouin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Michelle Lupton, Nicholas Martin, COGA Consortium, Spit for Science Working Group, Enrique Castelao, Katri Räikkönen, Johan Eriksson, Jari Lahti, Catharina Hartman, Albertine Oldehinkel, Harold Snieder, Hexuan Liu, Martin Preisig, Alyce Whipp, Eero Vuoksimaa, Yi Lu, Patrik Jern, Dan Rujescu, Ina Giegling, Teemu Palviainen, Jaakko Kaprio, Kathryn Paige Harden, Marcus Munafò, Geneviève Morneau-Vaillancourt, Robert Plomin, Essi Viding, Brian Boutwell, Fazil Aliev, Danielle Dick, Arne Popma, Stephen Faraone, Anders Børglum, Sarah Medland, Barbara Franke, Michel Boivin, Jean-Baptiste Pingault, Jeffrey Glennon, J. C. Barnes, Simon Fisher, Terrie Moffitt, Avshalom Caspi, Tinca Polderman, Danielle Posthuma

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

21 Citations (Scopus)
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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 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.
Original languageEnglish
Pages (from-to)4453-4463
Number of pages11
JournalMolecular Psychiatry
Volume27
Publication statusPublished - 2022
MoE publication typeA1 Journal article-refereed

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