Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Niamh Mullins; JooEun Kang; Adrian I Campos; Jonathan R I Coleman; Alexis C Edwards; Hanga Galfalvy; Daniel F Levey; Adriana Lori; Andrey Shabalin; Anna Starnawska; Mei-Hsin Su; Hunna J Watson; Mark Adams; Swapnil Awasthi; Michael Gandal; Jonathan D Hafferty; Akitoyo Hishimoto; Minsoo Kim; Satoshi Okazaki; Ikuo Otsuka; Stephan Ripke; Erin B Ware; Andrew W Bergen; Wade H Berrettini; Martin Bohus; Harry Brandt; Xiao Chang; Wei J Chen; Hsi-Chung Chen; Steven Crawford; Scott Crow; Emily DiBlasi; Philibert Duriez; Fernando Fernández-Aranda; Manfred M Fichter; Steven Gallinger; Stephen J Glatt; Philip Gorwood; Yiran Guo; Hakon Hakonarson; Katherine A Halmi; Hai-Gwo Hwu; Sonia Jain; Stéphane Jamain; Susana Jiménez-Murcia; Craig Johnson; Allan S Kaplan; Walter H Kaye; Pamela K Keel; James L Kennedy; Kelly L Klump; Dong Li; Shih-Cheng Liao; Klaus Lieb; Lisa Lilenfeld; Chih-Min Liu; Pierre J Magistretti; Christian R Marshall; James E Mitchell; Eric T Monson; Richard M Myers; Dalila Pinto; Abigail Powers; Nicolas Ramoz; Stefan Roepke; Vsevolod Rozanov; Stephen W Scherer; Christian Schmahl; Marcus Sokolowski; Michael Strober; Laura M Thornton; Janet Treasure; Ming T Tsuang; Stephanie H Witt; D Blake Woodside; Zeynep Yilmaz; Lea Zillich; Rolf Adolfsson; Ingrid Agartz; Tracy M Air; Martin Alda; Lars Alfredsson; Ole A Andreassen; Adebayo Anjorin; Vivek Appadurai; María Soler Artigas; Sandra Van der Auwera; M Helena Azevedo; Nicholas Bass; Claiton H D Bau; Bernhard T Baune; Frank Bellivier; Klaus Berger; Joanna M Biernacka; Tim B Bigdeli; Elisabeth B Binder; Michael Boehnke; Marco P Boks; Rosa Bosch; David L Braff; Richard Bryant; Monika Budde; Enda M Byrne; Wiepke Cahn; Miguel Casas; Enrique Castelao; Jorge A Cervilla; Boris Chaumette; Sven Cichon; Aiden Corvin; Nicholas Craddock; David Craig; Franziska Degenhardt; Srdjan Djurovic; Howard J Edenberg; Ayman H Fanous; Jerome C Foo; Andreas J Forstner; Mark Frye; Janice M Fullerton; Justine M Gatt; Pablo V Gejman; Ina Giegling; Hans J Grabe; Melissa J Green; Eugenio H Grevet; Maria Grigoroiu-Serbanescu; Blanca Gutierrez; Jose Guzman-Parra; Steven P Hamilton; Marian L Hamshere; Annette Hartmann; Joanna Hauser; Stefanie Heilmann-Heimbach; Per Hoffmann; Marcus Ising; Ian Jones; Lisa A Jones; Lina Jonsson; René S Kahn; John R Kelsoe; Kenneth S Kendler; Stefan Kloiber; Karestan C Koenen; Manolis Kogevinas; Bettina Konte; Marie-Odile Krebs; Mikael Landén; Jacob Lawrence; Marion Leboyer; Phil H Lee; Douglas F Levinson; Calwing Liao; Jolanta Lissowska; Susanne Lucae; Fermin Mayoral; Susan L McElroy; Patrick McGrath; Peter McGuffin; Andrew McQuillin; Sarah E Medland; Divya Mehta; Ingrid Melle; Yuri Milaneschi; Philip B Mitchell; Esther Molina; Gunnar Morken; Preben Bo Mortensen; Bertram Müller-Myhsok; Caroline Nievergelt; Vishwajit Nimgaonkar; Markus M Nöthen; Michael C O'Donovan; Roel A Ophoff; Michael J Owen; Carlos Pato; Michele T Pato; Brenda W J H Penninx; Jonathan Pimm; Giorgio Pistis; James B Potash; Robert A Power; Martin Preisig; Digby Quested; Josep Antoni Ramos-Quiroga; Andreas Reif; Marta Ribasés; Vanesa Richarte; Marcella Rietschel; Margarita Rivera; Andrea Roberts; Gloria Roberts; Guy A Rouleau; Diego L Rovaris; Dan Rujescu; Cristina Sánchez-Mora; Alan R Sanders; Peter R Schofield; Thomas G Schulze; Laura J Scott; Alessandro Serretti; Jianxin Shi; Stanley I Shyn; Lea Sirignano; Pamela Sklar; Olav B Smeland; Jordan W Smoller; Edmund J S Sonuga-Barke; Gianfranco Spalletta; John S Strauss; Beata Świątkowska; Maciej Trzaskowski; Gustavo Turecki; Laura Vilar-Ribó; John B Vincent; Henry Völzke; James T R Walters; Cynthia Shannon Weickert; Thomas W Weickert; Myrna M Weissman; Leanne M Williams; Naomi R Wray; Clement C Zai; Allison E Ashley-Koch; Jean C Beckham; Elizabeth R Hauser; Michael A Hauser; Nathan A Kimbrel; Jennifer H Lindquist; Benjamin McMahon; David W Oslin; Xuejun Qin; Esben Agerbo; Anders D Børglum; Gerome Breen; Annette Erlangsen; Tõnu Esko; Joel Gelernter; David M Hougaard; Ronald C Kessler; Henry R Kranzler; Qingqin S Li; Nicholas G Martin; Andrew M McIntosh; Ole Mors; Merete Nordentoft; Catherine M Olsen; David Porteous; Robert J Ursano; Danuta Wasserman; Thomas Werge; David C Whiteman; Cynthia M Bulik; Hilary Coon; Ditte Demontis; Anna R Docherty; Po-Hsiu Kuo; Cathryn M Lewis; J John Mann; Miguel E Rentería; Daniel J Smith; Eli A Stahl; Murray B Stein; Fabian Streit; Virginia Willour; Douglas M Ruderfer; VA Million Veteran Program; Philip D Harvey

doi:10.1016/j.biopsych.2021.05.029

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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Journal article

Open access

Peer reviewed

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Niamh Mullins, JooEun Kang, Adrian I Campos, Jonathan R I Coleman, Alexis C Edwards, Hanga Galfalvy, Daniel F Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, …

Biological psychiatry (1969), Vol.91(3), pp.313-327

2022-02-01

DOI: https://doi.org/10.1016/j.biopsych.2021.05.029

PMID: 34861974

Appears in Miller School of Medicine - Latest Publications

Abstract

Depressive Disorder, Major - genetics

Genome-Wide Association Study

Humans

Mental Disorders - genetics

Polymorphism, Single Nucleotide

Risk Factors

Suicide, Attempted

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.

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.21 Psychiatry; 1.21.430 Suicide
Web Of Science research areas: Neurosciences; Psychiatry
ESI research areas: Neuroscience & Behavior

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Title: Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Creators: Niamh Mullins
JooEun Kang - Vanderbilt University Medical Center
Adrian I Campos
Jonathan R I Coleman
Alexis C Edwards - Virginia Commonwealth University
Hanga Galfalvy
Daniel F Levey
Adriana Lori - Emory University School of Medicine
Andrey Shabalin - University of Utah
Anna Starnawska
Mei-Hsin Su - National Taiwan University
Hunna J Watson
Mark Adams - University of Edinburgh
Swapnil Awasthi - Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin, Berlin, Germany
Michael Gandal - Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
Jonathan D Hafferty - University of Edinburgh
Akitoyo Hishimoto - Yokohama City University
Minsoo Kim - Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California
Satoshi Okazaki - Kobe University
Ikuo Otsuka
Stephan Ripke
Erin B Ware
Andrew W Bergen
Wade H Berrettini - University of Pennsylvania
Martin Bohus - Heidelberg
Harry Brandt - Sheppard and Enoch Pratt Hospital
Xiao Chang - Children's Hospital of Philadelphia
Wei J Chen
Hsi-Chung Chen - National Taiwan University Hospital
Steven Crawford - Sheppard and Enoch Pratt Hospital
Scott Crow - University of Minnesota
Emily DiBlasi - University of Utah
Philibert Duriez
Fernando Fernández-Aranda - Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, Spain
Manfred M Fichter
Steven Gallinger - University of Toronto
Stephen J Glatt - SUNY Upstate Medical University
Philip Gorwood
Yiran Guo - Children's Hospital of Philadelphia
Hakon Hakonarson
Katherine A Halmi - Department of Psychiatry, Weill Cornell Medical College, New York, New York
Hai-Gwo Hwu - National Taiwan University Hospital
Sonia Jain - Human Longevity
Stéphane Jamain - University of Paris-Est
Susana Jiménez-Murcia - Department of Psychiatry, University Hospital Bellvitge-IDIBELL and CIBEROBN, Barcelona, Spain
Craig Johnson - Eating Recovery Center, Denver, Colorado
Allan S Kaplan
Walter H Kaye - University of California, San Diego
Pamela K Keel - Department of Psychology, Florida State University, Tallahassee, Florida
James L Kennedy
Kelly L Klump - Michigan State University
Dong Li - Children's Hospital of Philadelphia
Shih-Cheng Liao - National Taiwan University Hospital
Klaus Lieb - Department of Psychiatry and Psychotherapy, University Medical Center, Mainz, Germany
Lisa Lilenfeld - Department of Clinical Psychology, The Chicago School of Professional Psychology, Washington, DC
Chih-Min Liu - National Taiwan University Hospital
Pierre J Magistretti
Christian R Marshall - Hospital for Sick Children
James E Mitchell - University of North Dakota
Eric T Monson - University of Utah
Richard M Myers - HudsonAlpha Institute for Biotechnology
Dalila Pinto
Abigail Powers - Emory University School of Medicine
Nicolas Ramoz - Institute of Psychiatry and Neuroscience of Paris
Stefan Roepke - Humboldt-Universität zu Berlin
Vsevolod Rozanov
Stephen W Scherer - Hospital for Sick Children
Christian Schmahl - Heidelberg
Marcus Sokolowski - Karolinska Institutet
Michael Strober
Laura M Thornton - University of North Carolina at Chapel Hill
Janet Treasure
Ming T Tsuang - University of California, San Diego
Stephanie H Witt - Heidelberg
D Blake Woodside
Zeynep Yilmaz
Lea Zillich - Heidelberg
Rolf Adolfsson - Umeå University
Ingrid Agartz
Tracy M Air - University of Adelaide
Martin Alda
Lars Alfredsson
Ole A Andreassen
Adebayo Anjorin - Berkshire Healthcare NHS Foundation Trust
Vivek Appadurai
María Soler Artigas
Sandra Van der Auwera - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
M Helena Azevedo - University of Coimbra
Nicholas Bass - Division of Psychiatry, University College London, London, United Kingdom
Claiton H D Bau
Bernhard T Baune
Frank Bellivier
Klaus Berger - University of Münster
Joanna M Biernacka - Health Sciences Research, Mayo Clinic, Rochester, Minnesota
Tim B Bigdeli
Elisabeth B Binder
Michael Boehnke - University of Michigan–Ann Arbor
Marco P Boks - University Medical Center Utrecht
Rosa Bosch
David L Braff - University of California, San Diego
Richard Bryant - UNSW Australia
Monika Budde - Ludwig Maximilian University of Munich
Enda M Byrne
Wiepke Cahn - University Medical Center Utrecht
Miguel Casas
Enrique Castelao - University of Lausanne
Jorge A Cervilla - Universidad de Granada
Boris Chaumette
Sven Cichon
Aiden Corvin - Trinity College Dublin
Nicholas Craddock - Cardiff University
David Craig - Department of Translational Genomics, University of Southern California, Pasadena, California
Franziska Degenhardt - University Hospital Bonn
Srdjan Djurovic
Howard J Edenberg
Ayman H Fanous
Jerome C Foo - Heidelberg
Andreas J Forstner
Mark Frye - Department of Psychiatry & Psychology, Mayo Clinic, Rochester, Minnesota
Janice M Fullerton
Justine M Gatt
Pablo V Gejman
Ina Giegling
Hans J Grabe - Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
Melissa J Green
Eugenio H Grevet
Maria Grigoroiu-Serbanescu - Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania
Blanca Gutierrez - Universidad de Granada
Jose Guzman-Parra - Mental Health Department, University Regional Hospital, Biomedicine Institute, Málaga, Spain
Steven P Hamilton - Kaiser Permanente
Marian L Hamshere - Cardiff University
Annette Hartmann - Martin Luther University Halle-Wittenberg
Joanna Hauser - Poznan University of Medical Sciences
Stefanie Heilmann-Heimbach - University Hospital Bonn
Per Hoffmann
Marcus Ising - Max Planck Institute of Psychiatry
Ian Jones - Cardiff University
Lisa A Jones - University of Worcester
Lina Jonsson - University of Gothenburg
René S Kahn
John R Kelsoe
Kenneth S Kendler - Virginia Commonwealth University
Stefan Kloiber
Karestan C Koenen
Manolis Kogevinas - Center for Research in Environmental Epidemiology
Bettina Konte - Martin Luther University Halle-Wittenberg
Marie-Odile Krebs
Mikael Landén
Jacob Lawrence - Psychiatry, North East London NHS Foundation Trust, Ilford, Cheshire, United Kingdom
Marion Leboyer
Phil H Lee
Douglas F Levinson - Stanford University
Calwing Liao
Jolanta Lissowska - Cancer Epidemiology and Prevention, Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland
Susanne Lucae - Max Planck Institute of Psychiatry
Fermin Mayoral - Mental Health Department, University Regional Hospital, Biomedicine Institute, Málaga, Spain
Susan L McElroy - Lindner Center of HOPE
Patrick McGrath - Columbia University
Peter McGuffin - King's College London
Andrew McQuillin - UCL Australia
Sarah E Medland - QIMR Berghofer Medical Research Institute
Divya Mehta
Ingrid Melle
Yuri Milaneschi - GGZ inGeest
Philip B Mitchell - School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
Esther Molina - Universidad de Granada
Gunnar Morken
Preben Bo Mortensen
Bertram Müller-Myhsok
Caroline Nievergelt - University of California, San Diego
Vishwajit Nimgaonkar - University of Pittsburgh
Markus M Nöthen - University Hospital Bonn
Michael C O'Donovan - Cardiff University
Roel A Ophoff
Michael J Owen - Cardiff University
Carlos Pato
Michele T Pato - SUNY Downstate Medical Center
Brenda W J H Penninx - GGZ inGeest
Jonathan Pimm - Division of Psychiatry, University College London, London, United Kingdom
Giorgio Pistis - University of Lausanne
James B Potash - University of Iowa
Robert A Power
Martin Preisig - University of Lausanne
Digby Quested - University of Oxford
Josep Antoni Ramos-Quiroga
Andreas Reif - University Hospital Frankfurt
Marta Ribasés
Vanesa Richarte
Marcella Rietschel - Heidelberg
Margarita Rivera
Andrea Roberts - Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, Massachusetts
Gloria Roberts - School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
Guy A Rouleau
Diego L Rovaris - Universidade de São Paulo
Dan Rujescu - Martin Luther University Halle-Wittenberg
Cristina Sánchez-Mora
Alan R Sanders
Peter R Schofield
Thomas G Schulze
Laura J Scott - University of Michigan–Ann Arbor
Alessandro Serretti - University of Bologna
Jianxin Shi - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
Stanley I Shyn - Behavioral Health Services
Lea Sirignano - Heidelberg
Pamela Sklar
Olav B Smeland
Jordan W Smoller
Edmund J S Sonuga-Barke - King's College London
Gianfranco Spalletta
John S Strauss
Beata Świątkowska - Nofer Institute of Occupational Medicine
Maciej Trzaskowski - University of Queensland
Gustavo Turecki - McGill University
Laura Vilar-Ribó
John B Vincent - Centre for Addiction and Mental Health
Henry Völzke - Institute for Community Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
James T R Walters - Cardiff University
Cynthia Shannon Weickert
Thomas W Weickert
Myrna M Weissman
Leanne M Williams - Stanford University
Naomi R Wray
Clement C Zai
Allison E Ashley-Koch - Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina
Jean C Beckham
Elizabeth R Hauser
Michael A Hauser - Duke Medical Center
Nathan A Kimbrel
Jennifer 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 Carolina
Benjamin McMahon - Los Alamos National Laboratory
David W Oslin
Xuejun Qin - Duke Medical Center
Esben Agerbo
Anders D Børglum
Gerome Breen
Annette Erlangsen
Tõnu Esko
Joel Gelernter
David M Hougaard
Ronald C Kessler - Harvard Medical School
Henry R Kranzler
Qingqin S Li - Neuroscience, Janssen Research & Development, LLC, Titusville, New Jersey
Nicholas G Martin - QIMR Berghofer Medical Research Institute
Andrew M McIntosh - University of Edinburgh
Ole Mors
Merete Nordentoft
Catherine M Olsen - QIMR Berghofer Medical Research Institute
David Porteous - University of Edinburgh
Robert J Ursano - Department of Psychiatry, Uniformed University of the Health Sciences, Bethesda, Maryland
Danuta Wasserman - Karolinska Institutet
Thomas Werge
David C Whiteman - QIMR Berghofer Medical Research Institute
Cynthia M Bulik
Hilary Coon
Ditte Demontis
Anna R Docherty
Po-Hsiu Kuo
Cathryn M Lewis
J John Mann - Columbia University
Miguel E Rentería
Daniel J Smith - University of Glasgow
Eli A Stahl
Murray B Stein - University of California, San Diego
Fabian Streit - Heidelberg
Virginia Willour - University of Iowa
Douglas M Ruderfer
VA Million Veteran Program
Philip D Harvey - UMMG Dept of Psychiatry & Behavioral Sciences
Publication Details: Biological psychiatry (1969), Vol.91(3), pp.313-327
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
Academic Unit: Miller School of Medicine; UMMG Dept of Psychiatry & Behavioral Sciences
Language: English
Resource Type: Journal article
PMID: 34861974
Record Identifier: 991031757355902976