Journal article
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Biological psychiatry (1969), Vol.91(3), pp.313-327
02/01/2022
DOI: 10.1016/j.biopsych.2021.05.029
PMCID: PMC8851871
PMID: 34861974
Abstract
Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.
We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.
Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.
Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Details
- Title: Subtitle
- Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- Creators
- Niamh MullinsJooEun Kang - Vanderbilt University Medical CenterAdrian I CamposJonathan R I ColemanAlexis C Edwards - Virginia Commonwealth UniversityHanga GalfalvyDaniel F LeveyAdriana Lori - Emory University School of MedicineAndrey Shabalin - University of UtahAnna StarnawskaMei-Hsin Su - National Taiwan UniversityHunna J WatsonMark Adams - University of EdinburghSwapnil Awasthi - Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin, Berlin, GermanyMichael Gandal - Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CaliforniaJonathan D Hafferty - University of EdinburghAkitoyo Hishimoto - Yokohama City UniversityMinsoo Kim - Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CaliforniaSatoshi Okazaki - Kobe UniversityIkuo OtsukaStephan RipkeErin B WareAndrew W BergenWade H Berrettini - University of PennsylvaniaMartin Bohus - Heidelberg UniversityHarry Brandt - Sheppard and Enoch Pratt HospitalXiao Chang - Children's Hospital of PhiladelphiaWei J ChenHsi-Chung Chen - National Taiwan University HospitalSteven Crawford - Sheppard and Enoch Pratt HospitalScott Crow - University of MinnesotaEmily DiBlasi - University of UtahPhilibert DuriezFernando Fernández-Aranda - Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, SpainManfred M FichterSteven Gallinger - University of TorontoStephen J Glatt - SUNY Upstate Medical UniversityPhilip GorwoodYiran Guo - Children's Hospital of PhiladelphiaHakon HakonarsonKatherine A Halmi - Department of Psychiatry, Weill Cornell Medical College, New York, New YorkHai-Gwo Hwu - National Taiwan University HospitalSonia Jain - Human Longevity (United States)Stéphane Jamain - Paris-Est SupSusana Jiménez-Murcia - Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, SpainCraig Johnson - Eating Recovery Center, Denver, ColoradoAllan S KaplanWalter H Kaye - University of California San DiegoPamela K Keel - Department of Psychology, Florida State University, Tallahassee, FloridaJames L KennedyKelly L Klump - Michigan State UniversityDong Li - Children's Hospital of PhiladelphiaShih-Cheng Liao - National Taiwan University HospitalKlaus Lieb - Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, GermanyLisa Lilenfeld - Department of Clinical Psychology, The Chicago School of Professional Psychology, Washington, DCChih-Min Liu - National Taiwan University HospitalPierre J MagistrettiChristian R Marshall - Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, CanadaJames E Mitchell - University of North DakotaEric T Monson - University of UtahRichard M Myers - HudsonAlpha Institute for BiotechnologyDalila PintoAbigail Powers - Emory University School of MedicineNicolas Ramoz - Institut de Psychiatrie et Neurosciences de ParisStefan Roepke - Humboldt-Universität zu BerlinVsevolod RozanovStephen W Scherer - Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, CanadaChristian Schmahl - Heidelberg UniversityMarcus Sokolowski - Karolinska InstitutetMichael StroberLaura M Thornton - University of North Carolina at Chapel HillJanet TreasureMing T Tsuang - University of California San DiegoStephanie H Witt - Heidelberg UniversityD Blake WoodsideZeynep YilmazLea Zillich - Heidelberg UniversityRolf Adolfsson - Umeå UniversityIngrid AgartzTracy M Air - The University of AdelaideMartin AldaLars AlfredssonOle A AndreassenAdebayo Anjorin - Berkshire Healthcare NHS Foundation TrustVivek AppaduraiMaría Soler ArtigasSandra Van der Auwera - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, GermanyM Helena Azevedo - University of CoimbraNicholas Bass - University College LondonClaiton H D BauBernhard T BauneFrank BellivierKlaus Berger - University of MünsterJoanna M Biernacka - Mayo ClinicTim B BigdeliElisabeth B BinderMichael Boehnke - University of MichiganMarco P Boks - University Medical Center UtrechtRosa BoschDavid L Braff - University of California San DiegoRichard Bryant - School of Psychology, University of New South Wales, Sydney, New South Wales, AustraliaMonika Budde - Ludwig-Maximilians-Universität MünchenEnda M ByrneWiepke Cahn - University Medical Center UtrechtMiguel CasasEnrique Castelao - University of LausanneJorge A Cervilla - Universidad de GranadaBoris ChaumetteSven CichonAiden Corvin - Trinity College DublinNicholas Craddock - Cardiff UniversityDavid Craig - Department of Translational Genomics, University of Southern California, Pasadena, CaliforniaFranziska Degenhardt - University Hospital BonnSrdjan DjurovicHoward J EdenbergAyman H FanousJerome C Foo - Heidelberg UniversityAndreas J ForstnerMark Frye - Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MinnesotaJanice M FullertonJustine M GattPablo V GejmanIna GieglingHans J Grabe - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, GermanyMelissa J GreenEugenio H GrevetMaria Grigoroiu-Serbanescu - Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, RomaniaBlanca Gutierrez - Universidad de GranadaJose Guzman-Parra - Mental Health Department, University Regional Hospital, Biomedicine Institute, Málaga, SpainSteven P Hamilton - Kaiser PermanenteMarian L Hamshere - Cardiff UniversityAnnette Hartmann - Martin Luther University Halle-WittenbergJoanna Hauser - Poznan University of Medical SciencesStefanie Heilmann-Heimbach - University Hospital BonnPer HoffmannMarcus Ising - Max Planck Institute of PsychiatryIan Jones - Cardiff UniversityLisa A Jones - University of WorcesterLina Jonsson - University of GothenburgRené S KahnJohn R KelsoeKenneth S Kendler - Virginia Commonwealth UniversityStefan KloiberKarestan C KoenenManolis Kogevinas - Center for Research in Environmental EpidemiologyBettina Konte - Martin Luther University Halle-WittenbergMarie-Odile KrebsMikael LandénJacob Lawrence - Psychiatry, North East London NHS Foundation Trust, Ilford, Cheshire, United KingdomMarion LeboyerPhil H LeeDouglas F Levinson - Stanford UniversityCalwing LiaoJolanta Lissowska - Cancer Epidemiology and Prevention, Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, PolandSusanne Lucae - Max Planck Institute of PsychiatryFermin Mayoral - Mental Health Department, University Regional Hospital, Biomedicine Institute, Málaga, SpainSusan L McElroy - Lindner Center of HOPEPatrick McGrath - Columbia UniversityPeter McGuffin - King's College LondonAndrew McQuillin - University College LondonSarah E Medland - QIMR Berghofer Medical Research InstituteDivya MehtaIngrid MelleYuri Milaneschi - GGZ inGeestPhilip B Mitchell - School of Psychiatry, University of New South Wales, Sydney, New South Wales, AustraliaEsther Molina - Universidad de GranadaGunnar MorkenPreben Bo MortensenBertram Müller-MyhsokCaroline Nievergelt - University of California San DiegoVishwajit Nimgaonkar - University of PittsburghMarkus M Nöthen - University Hospital BonnMichael C O'Donovan - Cardiff UniversityRoel A OphoffMichael J Owen - Cardiff UniversityCarlos PatoMichele T Pato - SUNY Downstate Health Sciences UniversityBrenda W J H Penninx - GGZ inGeestJonathan Pimm - Division of Psychiatry, University College London, London, United KingdomGiorgio Pistis - University of LausanneJames B Potash - University of IowaRobert A PowerMartin Preisig - University of LausanneDigby Quested - University of OxfordJosep Antoni Ramos-QuirogaAndreas Reif - University Hospital FrankfurtMarta RibasésVanesa RicharteMarcella Rietschel - Heidelberg UniversityMargarita RiveraAndrea Roberts - Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, MassachusettsGloria Roberts - School of Psychiatry, University of New South Wales, Sydney, New South Wales, AustraliaGuy A RouleauDiego L Rovaris - Universidade de São PauloDan Rujescu - Martin Luther University Halle-WittenbergCristina Sánchez-MoraAlan R SandersPeter R SchofieldThomas G SchulzeLaura J Scott - University of MichiganAlessandro Serretti - University of BolognaJianxin Shi - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MarylandStanley I Shyn - Behavioral Health ServicesLea Sirignano - Heidelberg UniversityPamela SklarOlav B SmelandJordan W SmollerEdmund J S Sonuga-Barke - King's College LondonGianfranco SpallettaJohn S StraussBeata Świątkowska - Nofer Institute of Occupational MedicineMaciej Trzaskowski - The University of QueenslandGustavo Turecki - McGill UniversityLaura Vilar-RibóJohn B Vincent - Centre for Addiction and Mental HealthHenry Völzke - Institute for Community Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, GermanyJames T R Walters - Cardiff UniversityCynthia Shannon WeickertThomas W WeickertMyrna M WeissmanLeanne M Williams - Stanford UniversityNaomi R WrayClement C ZaiAllison E Ashley-Koch - Duke Medical CenterJean C BeckhamElizabeth R HauserMichael A Hauser - Duke Medical CenterNathan A KimbrelJennifer H Lindquist - VA Health Services Research and Development Center of Innovation to Accelerate Discovery and Practice Transformation, Durham Veterans Affairs Health Care System, Durham, North CarolinaBenjamin McMahon - Los Alamos National LaboratoryDavid W OslinXuejun Qin - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North CarolinaEsben AgerboAnders D BørglumGerome BreenAnnette ErlangsenTõnu EskoJoel GelernterDavid M HougaardRonald C Kessler - Harvard Medical SchoolHenry R KranzlerQingqin S LiNicholas G Martin - QIMR Berghofer Medical Research InstituteAndrew M McIntosh - University of EdinburghOle MorsMerete NordentoftCatherine M Olsen - QIMR Berghofer Medical Research InstituteDavid Porteous - University of EdinburghRobert J Ursano - Department of Psychiatry, Uniformed University of the Health Sciences, Bethesda, MarylandDanuta Wasserman - Karolinska InstitutetThomas WergeDavid C Whiteman - QIMR Berghofer Medical Research InstituteCynthia M BulikHilary CoonDitte DemontisAnna R DochertyPo-Hsiu KuoCathryn M LewisJ John Mann - Columbia UniversityMiguel E RenteríaDaniel J Smith - University of GlasgowEli A StahlMurray B Stein - University of California San DiegoFabian Streit - Heidelberg UniversityVirginia Willour - University of IowaDouglas M RuderferVA Million Veteran Program
- Contributors
- Zuhair Ballas (Contributor) - University of Iowa, Immunology
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.91(3), pp.313-327
- DOI
- 10.1016/j.biopsych.2021.05.029
- PMID
- 34861974
- PMCID
- PMC8851871
- NLM abbreviation
- Biol Psychiatry
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Grant note
- MR/L010305/1 / Medical Research Council R01 MH121455 / NIMH NIH HHS S10 OD026880 / NIH HHS R01 AA027522 / NIAAA NIH HHS T32 GM007347 / NIGMS NIH HHS R01 MH116269 / NIMH NIH HHS S10 OD018522 / NIH HHS MR/J000914/1 / Medical Research Council
- Language
- English
- Date published
- 02/01/2022
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984359810302771
Metrics
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