Медицинская библиотека · Molecular psychiatry · 2022

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

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

МетаанализСтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаПеревод пока не подготовлен

Аннотация

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.

Для цитирования: Tielbeek Jorim J, Uffelmann Emil, Williams Benjamin S, Colodro-Conde Lucía, Gagnon Éloi, Mallard Travis T, Levitt Brandt E, Jansen Philip R, Johansson Ada, Sallis Hannah M, Pistis Giorgio, Saunders Gretchen R B, Allegrini Andrea G, Rimfeld Kaili, Konte Bettina, Klein Marieke, Hartmann Annette M, Salvatore Jessica E, Nolte Ilja M, Demontis Ditte, Malmberg Anni L K, Burt S Alexandra, Savage Jeanne E, Sugden Karen, Poulton Richie, Harris Kathleen Mullan, Vrieze Scott, McGue Matt, Iacono William G, Mota Nina Roth, Mill Jonathan, Viana Joana F, Mitchell Brittany L, Morosoli Jose J, Andlauer Till F M, Ouellet-Morin Isabelle, Tremblay Richard E, Côté Sylvana M, Gouin Jean-Philippe, Brendgen Mara R, Dionne Ginette, Vitaro Frank, Lupton Michelle K, Martin Nicholas G, COGA Consortium, Spit for Science Working Group, Castelao Enrique, Räikkönen Katri, Eriksson Johan G, Lahti Jari, Hartman Catharina A, Oldehinkel Albertine J, Snieder Harold, Liu Hexuan, Preisig Martin, Whipp Alyce, Vuoksimaa Eero, Lu Yi, Jern Patrick, Rujescu Dan, Giegling Ina, Palviainen Teemu, Kaprio Jaakko, Harden Kathryn Paige, Munafò Marcus R, Morneau-Vaillancourt Geneviève, Plomin Robert, Viding Essi, Boutwell Brian B, Aliev Fazil, Dick Danielle M, Popma Arne, Faraone Stephen V, Børglum Anders D, Medland Sarah E, Franke Barbara, Boivin Michel, Pingault Jean-Baptiste, Glennon Jeffrey C, Barnes J C, Fisher Simon E, Moffitt Terrie E, Caspi Avshalom, Polderman Tinca J C, Posthuma Danielle. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.. Molecular psychiatry. 2022. DOI: 10.1038/s41380-022-01793-3.

Предметные рубрики MeSH

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

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