Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores
Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores
Abstract ObjectiveOver 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium. MethodSamples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed comparing attempters to non-attempters in each disorder followed by meta-analysis across disorders. Polygenic risk scoring investigated the genetic relationship between SA and the psychiatric disorders. ResultsThree genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. Polygenic risk scores for major depression were significantly associated with SA in MDD (P=0.0002), BIP (P=0.0006) and SCZ (P=0.0006). ConclusionsThis study provides new information on genetic associations and the genetic etiology of SA across psychiatric disorders. The finding that polygenic risk scores for major depression predict suicide attempt across disorders provides a possible starting point for predictive modelling and preventative strategies. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt.
Agerbo Esben、Strohmaier Jana、McGuffin Peter、Bellivier Frank、O?ˉDonovan Michael C、Jamain St¨|phane、Hamilton Steven P、McElroy Susan L、Cichon Sven、Air Tracy M、Nimgaonkar Vishwajit、Cahn Wiepke、Milaneschi Yuri、McQuillin Andrew、Ophoff Roel A、Adolfsson Rolf、Shyn Stanley I、Heilmann-Heimbach Stefanie、Fanous Ayman H.、Starnawska Anna、Anjorin Adebayo、Corvin Aiden、Reif Andreas、?wi?tkowska Beata、Penninx Brenda WJH、Pato Carlos、Zai Clement、Quested Digby、Levinson Douglas F、Binder Elisabeth B、Byrne Enda M、Breen Gerome、Morken Gunnar、Turecki Gustavo、Rouleau Guy A、Vincent John B、Walters James TR、Hauser Joanna、Biernacka Joanna M、Smoller Jordan W、Berger Klaus、Rietschel Marcella、Ising Marcus、Grigoroiu-Serbanescu Maria、Hamshere Marian L、Preisig Martin、Owen Michael J、Renteria Miguel、Hoffmann Per、Kelsoe John、Budde Monika、Strauss John S、Kloiber Stefan、Kogevinas Manolis、Azevedo M. Helena、Baune Bernhard T、Hansen Thomas、Grabe Hans J、Auwera Sandra Van der、Demontis Ditte、Melle Ingrid、Sanders Alan R、Power Robert A.、Wray Naomi R、Rujescu Dan、Boehnke Michael、Degenhardt Franziska、B?rglum Anders D、Werge Thomas、Lawrence Jacob、Giegling Ina、V?lzke Henry、Lee Phil H、Mullins Niamh、Gejman Pablo V、Sklar Pamela、Mors Ole、Pimm Jonathan、Boks Marco、Potash James B、Leboyer Marion、Djurovic Srdjan、Streit Fabian、Scott Laura J、Coleman Jonathan R I、M¨1ller-Myhsok Bertram、Parra Jos¨| Guzman、Ripke Stephan、Bigdeli Tim B.、Lucae Susanne、Trzaskowski Maciej、Lewis Cathryn M、Smeland Olav B、Shi Jianxin、Koller Anna C、Stahl Eli A、Kahn Ren¨| S、Bass Nicholas、Nordentoft Merete、Pato Michele T、Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium、Mayoral Fermin、Lissowska Jolanta、Agartz Ingrid、Kendler Kenneth S、McGrath Patrick、Mehta Divya、Andreassen Ole A、Appadurai Vivek、Forstner Andreas J、Schulze Thomas G、Konte Bettina、Frye Mark、Alda Martin、N?then Markus M、Weissman Myrna M
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Centre for Integrated Register-based Research, Aarhus University||National Centre for Register-Based Research, Aarhus UniversityDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversitySocial Genetic and Developmental Psychiatry Centre, King?ˉs College LondonDepartment of Psychiatry and Addiction Medicine, Assistance Publique - H?pitaux de Paris||Paris Bipolar and TRD Expert Centres||UMR-S1144 Team 1: Biomarkers of relapse and therapeutic response in addiction and mood disorders||Psychiatry, Universit¨| Paris DiderotMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityFacult¨| de M¨|decine, Universit¨| Paris Est||Psychiatrie TranslationnellePsychiatry, Kaiser Permanente Northern CaliforniaResearch Institute, Lindner Center of HOPEInstitute of Medical Genetics and Pathology, University Hospital Basel||Institute of Human Genetics, University of Bonn||Department of Biomedicine, University of Basel||Institute of Neuroscience and Medicine (INM-1), Research Centre J¨1lichDiscipline of Psychiatry, University of AdelaidePsychiatry and Human Genetics, University of PittsburghDepartment of Psychiatry, UMC Utrecht Hersencentrum Rudolf MagnusDepartment of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeestDivision of Psychiatry, University College LondonJane and Terry Semel Institute for Neuroscience and Human Behavior||UMC Utrecht Hersencentrum Rudolf MagnusDepartment of Clinical Sciences, Psychiatry, Ume? University Medical FacultyBehavioral Health ServicesDepartment of Biomedicine, University of BaselDepartment of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center||Department of Psychiatry, Virginia Commonwealth UniversityDepartment of Biomedicine, Aarhus University||iSEQ, Centre for Integrative Sequencing, Aarhus University||iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric ResearchPsychiatry, Berkshire Healthcare NHS Foundation TrustNeuropsychiatric Genetics Research Group, Dept of Psychiatry and Trinity Translational Medicine Institute, Trinity College DublinDepartment of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital FrankfurtNofer Institute of Occupational MedicineDepartment of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeestCollege of Medicine Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine||Institute for Genomic Health, SUNY Downstate Medical Center College of MedicineCentre for Addiction and Mental HealthDepartment of Psychiatry, University of OxfordPsychiatry & Behavioral Sciences, Stanford UniversityDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry||Department of Psychiatry and Behavioral Sciences, Emory University School of MedicineInstitute for Molecular Bioscience, The University of QueenslandSocial Genetic and Developmental Psychiatry Centre, King?ˉs College London||NIHR Maudsley Biomedical Research Centre, King?ˉs College LondonMental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology - NTNU||Psychiatry, St Olavs University HospitalDepartment of Psychiatry, McGill UniversityDepartment of Neurology and Neurosurgery, McGill University, Faculty of Medicine||Montreal Neurological Institute and HospitalCentre for Addiction and Mental HealthMRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff UniversityDepartment of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical SciencesHealth Sciences Research, Mayo ClinicDepartment of Psychiatry, Massachusetts General Hospital||Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad InstituteInstitute of Epidemiology and Social Medicine, University of M¨1nsterDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityMax Planck Institute of PsychiatryBiometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric HospitalMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityDepartment of Psychiatry, University Hospital of LausanneMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff UniversityGenetics and Computational Biology, QIMR Berghofer Medical Research InstituteInstitute of Medical Genetics and Pathology, University Hospital Basel||Institute of Human Genetics, University of Bonn||Life&Brain Center, Department of Genomics, University of Bonn||Department of Biomedicine, University of BaselDepartment of Psychiatry, University of California San DiegoInstitute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of MunichCentre for Addiction and Mental Health||Department of Psychiatry, University of TorontoCentre for Addiction and Mental Health||Department of Psychiatry, University of Toronto||Max Planck Institute of PsychiatryCenter for Research in Environmental Epidemiology (CREAL)Department of Psychiatry, University of CoimbraDepartment of Psychiatry, Melbourne Medical School, University of MelbourneiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services CopenhagenDepartment of Psychiatry and Psychotherapy, University Medicine GreifswaldDepartment of Psychiatry and Psychotherapy, University Medicine GreifswaldDepartment of Biomedicine, Aarhus University||iSEQ, Centre for Integrative Sequencing, Aarhus University||iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric ResearchDivision of Mental Health and Addiction, Oslo University Hospital||Division of Mental Health and Addiction, University of Oslo, Institute of Clinical MedicineDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago||Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystemSocial Genetic and Developmental Psychiatry Centre, King?ˉs College LondonQueensland Brain Institute, The University of Queensland||Institute for Molecular Bioscience, The University of QueenslandDepartment of Psychiatry, University of Halle||Department of Psychiatry, University of MunichCenter for Statistical Genetics and Department of Biostatistics, University of MichiganInstitute of Human Genetics, University of Bonn||Life&Brain Center, Department of Genomics, University of BonnDepartment of Biomedicine, Aarhus University||iSEQ, Centre for Integrative Sequencing, Aarhus University||iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric ResearchiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Department of Clinical Medicine, University of Copenhagen||Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services CopenhagenPsychiatry, North East London NHS Foundation TrustDepartment of Psychiatry, University of Halle||Department of Psychiatry, University of MunichInstitute for Community Medicine, University Medicine GreifswaldAnalytic and Translational Genetics Unit, Massachusetts General Hospital||Stanley Center for Psychiatric Research, Broad Institute||Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General HospitalSocial Genetic and Developmental Psychiatry Centre, King?ˉs College London||Genetics and Genomic Sciences, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry and Behavioral Neuroscience, University of Chicago||Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystemDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Department of Psychiatry, Icahn School of Medicine at Mount Sinai||Department of Neuroscience, Icahn School of Medicine at Mount SinaiiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Psychosis Research Unit, Aarhus University HospitalDivision of Psychiatry, University College LondonPsychiatry, UMC Utrecht Hersencentrum Rudolf MagnusPsychiatry, University of IowaDepartment of Psychiatry and Addiction Medicine, Assistance Publique - H?pitaux de Paris||Facult¨| de M¨|decine, Universit¨| Paris Est||INSERMNORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen||Department of Medical Genetics, Oslo University Hospital Ullev?lDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg UniversityCenter for Statistical Genetics and Department of Biostatistics, University of MichiganSocial Genetic and Developmental Psychiatry Centre, King?ˉs College LondonUniversity of Liverpool||Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry||Munich Cluster for Systems Neurology (SyNergy)Mental Health Department, University Regional Hospital. Biomedicine Institute (IBIMA)Analytic and Translational Genetics Unit, Massachusetts General Hospital||Department of Psychiatry and Psychotherapy, Universit?tsmedizin Berlin Campus Charit¨| Mitte||Medical and Population Genetics, Broad InstituteDepartment of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center||Department of Psychiatry, Virginia Commonwealth UniversityMax Planck Institute of PsychiatryInstitute for Molecular Bioscience, The University of QueenslandSocial Genetic and Developmental Psychiatry Centre, King?ˉs College London||Department of Medical & Molecular Genetics, King?ˉs College LondonDepartment of Neurosciences, University of California San Diego||Div Mental Health and Addiction, Oslo University Hospital||NORMENT, University of OsloDivision of Cancer Epidemiology and Genetics, National Cancer InstituteInstitute of Human Genetics, University of Bonn||Life&Brain Center, Department of Genomics, University of BonnMedical and Population Genetics, Broad Institute||Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai||Department of Psychiatry, Icahn School of Medicine at Mount SinaiDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai||Psychiatry, UMC Utrecht Hersencentrum Rudolf MagnusDivision of Psychiatry, University College LondoniPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research||Mental Health Center Copenhagen, Copenhagen Universtity HospitalInstitute for Genomic Health, SUNY Downstate Medical Center College of MedicineMental Health Department, University Regional Hospital. Biomedicine Institute (IBIMA)Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center and Institute of OncologyDepartment of Psychiatric Research, Diakonhjemmet Hospital||NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine and Diakonhjemmet Hospital, University of Oslo||Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska InstitutetDepartment of Psychiatry, Virginia Commonwealth UniversityPsychiatry, Columbia University College of Physicians and SurgeonsQueensland Brain Institute, The University of Queensland||School of Psychology and Counseling, Queensland University of TechnologyDiv Mental Health and Addiction, Oslo University Hospital||NORMENT, University of OsloiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric ResearchDepartment of Psychiatry (UPK), University of Basel||Institute of Medical Genetics and Pathology, University Hospital Basel||Human Genomics Research Group, Department of Biomedicine, University of Basel||Institute of Human Genetics, University of Bonn||Life&Brain Center, Department of Genomics, University of BonnDepartment of Psychiatry and Psychotherapy, University Medical Center G?ttingenDepartment of Psychiatry, University of HalleDepartment of Psychiatry & Psychology, Mayo ClinicDepartment of Psychiatry, Dalhousie University||National Institute of Mental HealthInstitute of Human Genetics, University of Bonn||Life&Brain Center, Department of Genomics, University of BonnPsychiatry, Columbia University College of Physicians and Surgeons||Division of Epidemiology, New York State Psychiatric Institute
神经病学、精神病学医学研究方法基础医学
Agerbo Esben,Strohmaier Jana,McGuffin Peter,Bellivier Frank,O?ˉDonovan Michael C,Jamain St¨|phane,Hamilton Steven P,McElroy Susan L,Cichon Sven,Air Tracy M,Nimgaonkar Vishwajit,Cahn Wiepke,Milaneschi Yuri,McQuillin Andrew,Ophoff Roel A,Adolfsson Rolf,Shyn Stanley I,Heilmann-Heimbach Stefanie,Fanous Ayman H.,Starnawska Anna,Anjorin Adebayo,Corvin Aiden,Reif Andreas,?wi?tkowska Beata,Penninx Brenda WJH,Pato Carlos,Zai Clement,Quested Digby,Levinson Douglas F,Binder Elisabeth B,Byrne Enda M,Breen Gerome,Morken Gunnar,Turecki Gustavo,Rouleau Guy A,Vincent John B,Walters James TR,Hauser Joanna,Biernacka Joanna M,Smoller Jordan W,Berger Klaus,Rietschel Marcella,Ising Marcus,Grigoroiu-Serbanescu Maria,Hamshere Marian L,Preisig Martin,Owen Michael J,Renteria Miguel,Hoffmann Per,Kelsoe John,Budde Monika,Strauss John S,Kloiber Stefan,Kogevinas Manolis,Azevedo M. Helena,Baune Bernhard T,Hansen Thomas,Grabe Hans J,Auwera Sandra Van der,Demontis Ditte,Melle Ingrid,Sanders Alan R,Power Robert A.,Wray Naomi R,Rujescu Dan,Boehnke Michael,Degenhardt Franziska,B?rglum Anders D,Werge Thomas,Lawrence Jacob,Giegling Ina,V?lzke Henry,Lee Phil H,Mullins Niamh,Gejman Pablo V,Sklar Pamela,Mors Ole,Pimm Jonathan,Boks Marco,Potash James B,Leboyer Marion,Djurovic Srdjan,Streit Fabian,Scott Laura J,Coleman Jonathan R I,M¨1ller-Myhsok Bertram,Parra Jos¨| Guzman,Ripke Stephan,Bigdeli Tim B.,Lucae Susanne,Trzaskowski Maciej,Lewis Cathryn M,Smeland Olav B,Shi Jianxin,Koller Anna C,Stahl Eli A,Kahn Ren¨| S,Bass Nicholas,Nordentoft Merete,Pato Michele T,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium,Mayoral Fermin,Lissowska Jolanta,Agartz Ingrid,Kendler Kenneth S,McGrath Patrick,Mehta Divya,Andreassen Ole A,Appadurai Vivek,Forstner Andreas J,Schulze Thomas G,Konte Bettina,Frye Mark,Alda Martin,N?then Markus M,Weissman Myrna M.Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/416008.点此复制
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