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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; Castelao, Enrique; Räikkönen, Katri; Eriksson, Johan G; Lahti, Jari; Hartman, Catharina A; Oldehinkel, Albertine J.
Affiliation
  • Tielbeek JJ; Center for Neurogenomics and Cognitive Research, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands. j.j.tielbeek@vu.nl.
  • Uffelmann E; Center for Neurogenomics and Cognitive Research, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands.
  • Williams BS; Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, 2020 West Main Street, Durham, NC, 27705, USA.
  • Colodro-Conde L; Psychiatric Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Gagnon É; Research Unit on Children's Psychosocial Maladjustment, École de psychologie, Université Laval, 2523 Allée des Bibliothèques, Quebec City, QC, G1V 0A6, Canada.
  • Mallard TT; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Levitt BE; Carolina Population Center, University of North Carolina at Chapel Hill, 123 Franklin St, Chapel Hill, NC, 27516, USA.
  • Jansen PR; Center for Neurogenomics and Cognitive Research, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands.
  • Johansson A; Department of Psychology, Faculty of Arts, Psychology, and Theology, Åbo Akademi University, Tuomiokirkontori 3, FI-20500, Turku, Finland.
  • Sallis HM; MRC Integrative Epidemiology Unit, University of Bristol, Oakfield Road, Bristol, BS8 2BN, UK.
  • Pistis G; Center for Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Route de Cery 25, CH-1008, Prilly, Vaud, Switzerland.
  • Saunders GRB; Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
  • Allegrini AG; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, DeCrespigny Park, Denmark Hill, London, SE5 8AF, UK.
  • Rimfeld K; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, DeCrespigny Park, Denmark Hill, London, SE5 8AF, UK.
  • Konte B; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Klein M; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Groteplein 10, 6500 HB, Nijmegen, The Netherlands.
  • Hartmann AM; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Salvatore JE; Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
  • Nolte IM; Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
  • Demontis D; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8000, Aarhus C, Aarhus, Denmark.
  • Malmberg ALK; Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
  • Burt SA; Michigan State University, East Lansing, MI, USA.
  • Savage JE; Center for Neurogenomics and Cognitive Research, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands.
  • Sugden K; Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, 2020 West Main Street, Durham, NC, 27705, USA.
  • Poulton R; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, Dunedin, New Zealand.
  • Harris KM; Department of Sociology, University of North Carolina at Chapel Hill, CB# 3210, 201 Hamilton Hall, Chapel Hill, NC, 27599, USA.
  • Vrieze S; Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
  • McGue M; Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
  • Iacono WG; Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
  • Mota NR; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Geert Groteplein 10, 6500 HB, Nijmegen, The Netherlands.
  • Mill J; University of Exeter Medical School, University of Exeter, Exeter, UK.
  • Viana JF; The Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Edgbaston, Birmingham, UK.
  • Mitchell BL; Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Morosoli JJ; Psychiatric Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Andlauer TFM; Department of Neurology, Technical University of Munich, 22 Ismaninger St., 81675, Munich, Germany.
  • Ouellet-Morin I; Research Unit on Children's Psychosocial Maladjustment, École de criminologie, Université of Montreal, 3150 Rue Jean-Brillant, Montreal, QC, H3T 1N8, Canada.
  • Tremblay RE; Research Unit on Children's Psychosocial Maladjustment, Département de pédiatrie et de psychologie, University of Montreal, 90 Avenue Vincent d'Indy, Montreal, QC, H2V 2S9, Canada.
  • Côté SM; Research Unit on Children's Psychosocial Maladjustment, CHU Ste-Justine Research Center and Department of Social and Preventive Medicine, University of Montreal, 3175 Chemin de la Côte Ste-Catherine, Montreal, QC, H3T 1C5, Canada.
  • Gouin JP; Department of Psychology, Concordia University, 7141 Sherbrooke St. West, Montreal, QC, H4B 1R6, Canada.
  • Brendgen MR; Research Unit on Children's Psychosocial Maladjustment, Département de psychologie, Université du Québec à Montréal, CP 8888 succursale Centre-ville, Montreal, QC, H3C 3P8, Canada.
  • Dionne G; Research Unit on Children's Psychosocial Maladjustment, École de psychologie, Université Laval, 2523 Allée des Bibliothèques, Quebec City, QC, G1V 0A6, Canada.
  • Vitaro F; Research Unit on Children's Psychosocial Maladjustment, CHU Sainte-Justine Research Center and University of Montreal, 3175 Chemin de la Côte Ste-Catherine, Montreal, QC, H3T 1C5, Canada.
  • Lupton MK; Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Martin NG; Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
  • Castelao E; Center for Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Route de Cery 25, CH-1008, Prilly, Vaud, Switzerland.
  • Räikkönen K; Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
  • Eriksson JG; Department of General Practice and Primary Health Care, University of Helsinki, Tukholmankatu 8 B, Helsinki, Finland.
  • Lahti J; Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
  • Hartman CA; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
  • Oldehinkel AJ; Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Mol Psychiatry ; 27(11): 4453-4463, 2022 11.
Article in En | MEDLINE | ID: mdl-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 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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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Conduct Disorder / Antisocial Personality Disorder Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Animals Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2022 Document type: Article Affiliation country: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Conduct Disorder / Antisocial Personality Disorder Type of study: Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Animals Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2022 Document type: Article Affiliation country: Netherlands