Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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36284158
TITLE
Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.
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 ). 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  = 0.63, insomnia r  = 0.47), physical health (overweight r  = 0.19, waist-to-hip ratio r  = 0.32), smoking (r  = 0.54), cognitive ability (intelligence r  = -0.40), educational attainment (years of schooling r  = -0.46) and reproductive traits (age at first birth r  = -0.58, father's age at death r  = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
DATE PUBLISHED
2022 Oct 25
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2022/02/24
accepted 2022/09/09
revised 2022/08/03
entrez 2022/10/25 23:59
pubmed 2022/10/26 06:00
medline 2022/10/26 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Tielbeek JJ Tielbeek Jorim J 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 Uffelmann Emil 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 Williams Benjamin S 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 Colodro-Conde Lucía L Psychiatric Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Gagnon É Gagnon Éloi 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 Mallard Travis T TT Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Levitt BE Levitt Brandt E BE Carolina Population Center, University of North Carolina at Chapel Hill, 123 Franklin St, Chapel Hill, NC, 27516, USA.
Jansen PR Jansen Philip R 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 Johansson Ada A Department of Psychology, Faculty of Arts, Psychology, and Theology, Åbo Akademi University, Tuomiokirkontori 3, FI-20500, Turku, Finland.
Sallis HM Sallis Hannah M HM MRC Integrative Epidemiology Unit, University of Bristol, Oakfield Road, Bristol, BS8 2BN, UK.
Pistis G Pistis Giorgio 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 Saunders Gretchen R B GRB Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
Allegrini AG Allegrini Andrea G AG Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, DeCrespigny Park, Denmark Hill, London, SE5 8AF, UK.
Rimfeld K Rimfeld Kaili K Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, DeCrespigny Park, Denmark Hill, London, SE5 8AF, UK.
Konte B Konte Bettina B Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Klein M Klein Marieke 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 Hartmann Annette M AM Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Salvatore JE Salvatore Jessica E JE Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA.
Nolte IM Nolte Ilja M IM Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Demontis D Demontis Ditte D iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8000, Aarhus C, Aarhus, Denmark.
Malmberg ALK Malmberg Anni L K ALK Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
Burt SA Burt S Alexandra SA Michigan State University, East Lansing, MI, USA.
Savage JE Savage Jeanne E 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 Sugden Karen K Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, 2020 West Main Street, Durham, NC, 27705, USA.
Poulton R Poulton Richie R Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, Dunedin, New Zealand.
Harris KM Harris Kathleen Mullan KM Department of Sociology, University of North Carolina at Chapel Hill, CB# 3210, 201 Hamilton Hall, Chapel Hill, NC, 27599, USA.
Vrieze S Vrieze Scott S Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
McGue M McGue Matt M Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota, 75 E. River Road, Minneapolis, MN, 55455, USA.
Mota NR Mota Nina Roth 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 Mill Jonathan J University of Exeter Medical School, University of Exeter, Exeter, UK.
Viana JF Viana Joana F JF The Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Edgbaston, Birmingham, UK.
Mitchell BL Mitchell Brittany L BL Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Morosoli JJ Morosoli Jose J JJ Psychiatric Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Andlauer TFM Andlauer Till F M TFM Department of Neurology, Technical University of Munich, 22 Ismaninger St., 81675, Munich, Germany.
Ouellet-Morin I Ouellet-Morin Isabelle 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 Tremblay Richard E 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 Côté Sylvana M 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 Gouin Jean-Philippe JP Department of Psychology, Concordia University, 7141 Sherbrooke St. West, Montreal, QC, H4B 1R6, Canada.
Brendgen MR Brendgen Mara R 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 Dionne Ginette 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 Vitaro Frank 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 Lupton Michelle K MK Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Martin NG Martin Nicholas G NG Genetic Epidemiology, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
COGA Consortium
Spit for Science Working Group
Castelao E Castelao Enrique 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 Räikkönen Katri K Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
Eriksson JG Eriksson Johan G JG Department of General Practice and Primary Health Care, University of Helsinki, Tukholmankatu 8 B, Helsinki, Finland.
Lahti J Lahti Jari J Department of Psychology and Logopedics, University of Helsinki, Haartmaninkatu 3, 00014, Helsinki, Finland.
Hartman CA Hartman Catharina A CA Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Oldehinkel AJ Oldehinkel Albertine J AJ Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Liu H Liu Hexuan H School of Criminal Justice, University of Cincinnati, 2840 Bearcat Way, Cincinnati, OH, 45221, USA.
Preisig M Preisig Martin M 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.
Whipp A Whipp Alyce A Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 4, (Yliopistonkatu 3), 00014, Helsinki, Finland.
Vuoksimaa E Vuoksimaa Eero E Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 4, (Yliopistonkatu 3), 00014, Helsinki, Finland.
Lu Y Lu Yi Y Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Väg 12A, 171 77, Stockholm, Sweden.
Jern P Jern Patrick P Department of Psychology, Faculty of Arts, Psychology, and Theology, Åbo Akademi University, Tuomiokirkontori 3, FI-20500, Turku, Finland.
Rujescu D Rujescu Dan D Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Giegling I Giegling Ina I Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 4, (Yliopistonkatu 3), 00014, Helsinki, Finland.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, PO Box 4, (Yliopistonkatu 3), 00014, Helsinki, Finland.
Harden KP Harden Kathryn Paige KP Department of Psychology and Population Research Center, University of Texas at Austin, 108 E Dean Keeton Stop #A8000, Austin, TX, 78712, USA.
Munafò MR Munafò Marcus R MR MRC Integrative Epidemiology Unit, University of Bristol, Oakfield Road, Bristol, BS8 2BN, UK.
Morneau-Vaillancourt G Morneau-Vaillancourt Geneviève G Research Unit on Children's Psychosocial Maladjustment, École de psychologie, Université Laval, 2523 Allée des Bibliothèques, Quebec City, QC, G1V 0A6, Canada.
Plomin R Plomin Robert R Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, DeCrespigny Park, Denmark Hill, London, SE5 8AF, UK.
Viding E Viding Essi E Division of Psychology and Language Sciences, University College London, London, UK.
Boutwell BB Boutwell Brian B BB School of Applied Sciences, University of Mississippi, John D. Bower School of Population Health, University of Mississippi Medical Center, 84 Dormitory Row West, University, MS, 38677, USA.
Aliev F Aliev Fazil F Department of Psychology, Virginia Commonwealth University, Box 842018, 806W Franklin St, Richmond, VA, 23284, USA.
Dick DM Dick Danielle M DM Department of Psychology, Virginia Commonwealth University, Box 842018, 806W Franklin St, Richmond, VA, 23284, USA.
Popma A Popma Arne A Amsterdam UMC, VKC Psyche, Child and Adolescent Psychiatry & Psychosocial Care, Amsterdam, The Netherlands.
Faraone SV Faraone Stephen V SV Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
Børglum AD Børglum Anders D AD iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, 8000, Aarhus C, Aarhus, Denmark.
Medland SE Medland Sarah E SE Psychiatric Genetics, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia.
Franke B Franke Barbara B Department of Human Genetics, Donders Institute for Brain, Cognition and Behaivour, Radboud University Medical Center, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands.
Boivin M Boivin Michel M Research Unit on Children's Psychosocial Maladjustment, École de psychologie, Université Laval, 2523 Allée des Bibliothèques, Quebec City, QC, G1V 0A6, Canada.
Pingault JB Pingault Jean-Baptiste JB Department of Clinical, Educational and Health Psychology, University College London, London, UK.
Glennon JC Glennon Jeffrey C JC Conway Institute of Biomolecular and Biomedical Sciences, School of Medicine, University College Dublin, Dublin, Ireland.
Barnes JC Barnes J C JC School of Criminal Justice, University of Cincinnati, 2840 Bearcat Way, Cincinnati, OH, 45221, USA.
Fisher SE Fisher Simon E SE Language and Genetics Department, Max Planck Institute for Psycholinguistics, Wundtlaan 1, 6525 XD, Nijmegen, The Netherlands.
Moffitt TE Moffitt Terrie E TE Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, 2020 West Main Street, Durham, NC, 27705, USA.
Caspi A Caspi Avshalom A Department of Psychology and Neuroscience, Trinity College of Arts and Sciences, Duke University, 2020 West Main Street, Durham, NC, 27705, USA.
Polderman TJC Polderman Tinca J C TJC Amsterdam UMC, VKC Psyche, Child and Adolescent Psychiatry & Psychosocial Care, Amsterdam, The Netherlands.
Posthuma D Posthuma Danielle D Center for Neurogenomics and Cognitive Research, Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Porjesz Bernice B
Hesselbrock Victor V
Foroud Tatiana T
Agrawal Arpana A
Edenberg Howard J HJ
Liu Yunlong Y
Plawecki Martin H MH
Kuperman Samuel S
Kramer John R JR
Meyers Jacquelyn M JM
Kamarajan Chella C
Pandey Ashwini A
Bierut Laura L
Rice John J
Bucholz Kathleen K KK
Schuckit Marc A MA
Tischfield Jay J
Hart Ronald R
Almasy Laura L
Goate Alison A
Slesinger Paul P
Scott Denise D
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol Psychiatry
YEAR: 2022
MONTH: Oct
DAY: 25
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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