GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Anna R. Docherty(Virginia Commonwealth University), Niamh Mullins(Virginia Commonwealth University), Allison E. Ashley‐Koch(Virginia Commonwealth University), Xuejun Qin(Virginia Commonwealth University), Jonathan R. I. Coleman(Virginia Commonwealth University), Andrey A. Shabalin(Virginia Commonwealth University), Jooeun Kang(Virginia Commonwealth University), Balasz Murnyak(Virginia Commonwealth University), Frank R. Wendt(Virginia Commonwealth University), Mark J. Adams(Virginia Commonwealth University), Adrián I. Campos(Virginia Commonwealth University), Emily DiBlasi(Virginia Commonwealth University), Janice M. Fullerton(Virginia Commonwealth University), Henry R. Kranzler(Virginia Commonwealth University), Amanda V. Bakian(Virginia Commonwealth University), Eric T. Monson(Virginia Commonwealth University), Miguel E. Rentería(Virginia Commonwealth University), Consuelo Walss‐Bass(Virginia Commonwealth University), Ole A. Andreassen(Virginia Commonwealth University), Chittaranjan Behera(Virginia Commonwealth University), Cynthia M. Bulik(Virginia Commonwealth University), Howard J. Edenberg(Virginia Commonwealth University), Ronald C. Kessler(Virginia Commonwealth University), J. John Mann(Virginia Commonwealth University), John I. Nürnberger(Virginia Commonwealth University), Giorgio Pistis(Virginia Commonwealth University), Fabian Streit(Virginia Commonwealth University), Robert J. Ursano(Virginia Commonwealth University), Renato Polimanti(Virginia Commonwealth University), Michelle F. Dennis(Virginia Commonwealth University), Melanie E. Garrett(Virginia Commonwealth University), Lauren P. Hair(Virginia Commonwealth University), Philip D. Harvey(Virginia Commonwealth University), Elizabeth R. Hauser(Virginia Commonwealth University), Michael A. Hauser(Virginia Commonwealth University), Jennifer E. Huffman(Virginia Commonwealth University), Daniel Jacobson(Virginia Commonwealth University), Ravi Madduri(Virginia Commonwealth University), Benjamin H. McMahon(Virginia Commonwealth University), David W. Oslin(Virginia Commonwealth University), Jodie Trafton(Virginia Commonwealth University), Swapnil Awasthi(Virginia Commonwealth University), Wade H. Berrettini(Virginia Commonwealth University), Martin Bohus(Virginia Commonwealth University), Xiao Chang(Virginia Commonwealth University), Hsi‐Chung Chen(Virginia Commonwealth University), Wei J. Chen(Virginia Commonwealth University), Erik D. Christensen(Virginia Commonwealth University), Scott J. Crow(Virginia Commonwealth University), Philibert Duriez(Virginia Commonwealth University), Alexis C. Edwards(Virginia Commonwealth University), Fernando Fernández‐Aranda(Virginia Commonwealth University), Hanga Galfalvy(Virginia Commonwealth University), Michael J. Gandal(Virginia Commonwealth University), Philip Gorwood(Virginia Commonwealth University), Yiran Guo(Virginia Commonwealth University), Jonathan D. Hafferty(Virginia Commonwealth University), Håkon Håkonarson(Virginia Commonwealth University), Katherine A. Halmi(Virginia Commonwealth University), Akitoyo Hishimoto(Virginia Commonwealth University), Sonia Jain(Virginia Commonwealth University), Stéphane Jamain(Virginia Commonwealth University), Susana Jiménez‐Múrcia(Virginia Commonwealth University), Craig Johnson(Virginia Commonwealth University), Allan S. Kaplan(Virginia Commonwealth University), Walter H. Kaye(Virginia Commonwealth University), Pamela K. Keel(Virginia Commonwealth University), James L. Kennedy(Virginia Commonwealth University), Minsoo Kim(Virginia Commonwealth University), Kelly L. Klump(Virginia Commonwealth University), Daniel F. Levey(Virginia Commonwealth University), Dong Li(Virginia Commonwealth University), Shih‐Cheng Liao(Virginia Commonwealth University), Klaus Lieb(Virginia Commonwealth University), Lisa Lilenfeld(Virginia Commonwealth University), Christian R. Marshall(Virginia Commonwealth University), James E. Mitchell(Virginia Commonwealth University), Satoshi Okazaki(Virginia Commonwealth University), Ikuo Otsuka(Virginia Commonwealth University), Dalila Pinto(Virginia Commonwealth University), Abigail Powers(Virginia Commonwealth University), Nicolás Ramoz(Virginia Commonwealth University), Stephan Ripke(Virginia Commonwealth University), Stefan Roepke(Virginia Commonwealth University), Vsevolod Rozanov(Virginia Commonwealth University), Stephen W. Scherer(Virginia Commonwealth University), Christian Schmahl(Virginia Commonwealth University), Marcus Sokolowski(Virginia Commonwealth University), Anna Starnawska(Virginia Commonwealth University), Michael Strober(Virginia Commonwealth University), Mei‐Hsin Su(Virginia Commonwealth University), Laura M. Thornton(Virginia Commonwealth University), Janet Treasure(Virginia Commonwealth University), Erin B. Ware(Virginia Commonwealth University), Hunna J. Watson(Virginia Commonwealth University), Stephanie H. Witt(Virginia Commonwealth University), D. Blake Woodside(Virginia Commonwealth University), Zeynep Yılmaz(Virginia Commonwealth University), Lea Zillich(Virginia Commonwealth University), Rolf Adolfsson(Virginia Commonwealth University), Ingrid Agartz(Virginia Commonwealth University), Martin Alda(Virginia Commonwealth University), Lars Alfredsson(Virginia Commonwealth University), Vivek Appadurai(Virginia Commonwealth University), María Soler Artigas(Virginia Commonwealth University), Sandra Van der Auwera(Virginia Commonwealth University), M.H. Azevedo(Virginia Commonwealth University), Nicholas Bass(Virginia Commonwealth University), Claiton H.D. Bau(Virginia Commonwealth University), Bernhard T. Baune(Virginia Commonwealth University), Frank Bellivier(Virginia Commonwealth University), Klaus Berger(Virginia Commonwealth University), Joanna M. Biernacka(Virginia Commonwealth University), Tim B. Bigdeli(Virginia Commonwealth University), Elisabeth B. Binder(Virginia Commonwealth University), Michael Boehnke(Virginia Commonwealth University), Marco P. Boks(Virginia Commonwealth University), David Braff(Virginia Commonwealth University), Richard A. Bryant(Virginia Commonwealth University), Monika Budde(Virginia Commonwealth University), Enda M. Byrne(Virginia Commonwealth University), Wiepke Cahn(Virginia Commonwealth University), Enrique Castelao(Virginia Commonwealth University), Jorge A. Cervilla(Virginia Commonwealth University), Boris Chaumette(Virginia Commonwealth University), Aiden Corvin(Virginia Commonwealth University), Nicholas Craddock(Virginia Commonwealth University), Srdjan Djurovic(Virginia Commonwealth University), Jerome C. Foo(Virginia Commonwealth University), Andreas J. Forstner(Virginia Commonwealth University), Mark A. Frye(Virginia Commonwealth University), Justine M. Gatt(Virginia Commonwealth University), Ina Giegling(Virginia Commonwealth University), Hans J. Grabe(Virginia Commonwealth University), Melissa J. Green(Virginia Commonwealth University), Eugênio H. Grevet(Virginia Commonwealth University), Maria Grigoroiu‐Serbânescu(Virginia Commonwealth University), Blanca Gutiérrez(Virginia Commonwealth University), José Guzmán‐Parra(Virginia Commonwealth University), Marian L. Hamshere(Virginia Commonwealth University), Annette M. Hartmann(Virginia Commonwealth University), Joanna Hauser(Virginia Commonwealth University), Stefanie Heilmann‐Heimbach(Virginia Commonwealth University), Per Hoffmann(Virginia Commonwealth University), Marcus Ising(Virginia Commonwealth University), Ian Jones(Virginia Commonwealth University), Lisa Jones(Virginia Commonwealth University), Lina Jönsson(Virginia Commonwealth University), René S. Kahn(Virginia Commonwealth University), John R. Kelsoe(Virginia Commonwealth University), Kenneth S. Kendler(Virginia Commonwealth University), Stefan Kloiber(Virginia Commonwealth University), Karestan C. Koenen(Virginia Commonwealth University), Manolis Kogevinas(Virginia Commonwealth University), Marie‐Odile Krebs(Virginia Commonwealth University), Mikael Landén(Virginia Commonwealth University), Marion Leboyer(Virginia Commonwealth University), Phil H. Lee(Virginia Commonwealth University), Douglas F. Levinson(Virginia Commonwealth University), Calwing Liao(Virginia Commonwealth University), Jolanta Lissowska(Virginia Commonwealth University), Fermín Mayoral(Virginia Commonwealth University), Susan L. McElroy(Virginia Commonwealth University), Patrick J. McGrath(Virginia Commonwealth University), Peter McGuffin(Virginia Commonwealth University), Andrew McQuillin(Virginia Commonwealth University), Divya Mehta(Virginia Commonwealth University), Ingrid Melle(Virginia Commonwealth University), Philip B. Mitchell(Virginia Commonwealth University), Esther Molina(Virginia Commonwealth University), Gunnar Morken(Virginia Commonwealth University), Caroline M. Nievergelt(Virginia Commonwealth University), Markus M. Nöthen(Virginia Commonwealth University), Michael O‘Donovan(Virginia Commonwealth University), Roel A. Ophoff(Virginia Commonwealth University), Michael J. Owen(Virginia Commonwealth University), Carlos N. Pato(Virginia Commonwealth University), Michele T. Pato(Virginia Commonwealth University), Brenda W.J.H. Penninx(Virginia Commonwealth University), James B. Potash(Virginia Commonwealth University), Robert A. Power(Virginia Commonwealth University), Martin Preisig(Virginia Commonwealth University), Digby Quested(Virginia Commonwealth University), Josep Antoni Ramos‐Quiroga(Virginia Commonwealth University), Andreas Reif(Virginia Commonwealth University), Marta Ribasés(Virginia Commonwealth University), Vanesa Richarte(Virginia Commonwealth University), Marcella Rietschel(Virginia Commonwealth University), Margarita Rivera(Virginia Commonwealth University), Andrea L. Roberts(Virginia Commonwealth University), Gloria Roberts(Virginia Commonwealth University), Guy A. Rouleau(Virginia Commonwealth University), Diego Luiz Rovaris(Virginia Commonwealth University), Alan R. Sanders(Virginia Commonwealth University), Peter R. Schofield(Virginia Commonwealth University), Thomas G. Schulze(Virginia Commonwealth University), Laura J. Scott(Virginia Commonwealth University), Alessandro Serretti(Virginia Commonwealth University), Jianxin Shi(Virginia Commonwealth University), Lea Sirignano(Virginia Commonwealth University), Pamela Sklar(Virginia Commonwealth University), Olav B. Smeland(Virginia Commonwealth University), Jordan W. Smoller(Virginia Commonwealth University), Edmund Sonuga‐Barke(Virginia Commonwealth University), Maciej Trzaskowski(Virginia Commonwealth University), Ming T. Tsuang(Virginia Commonwealth University), Gustavo Turecki(Virginia Commonwealth University), Laura Vilar‐Ribó(Virginia Commonwealth University), John B. Vincent(Virginia Commonwealth University), Henry Völzke(Virginia Commonwealth University), James Walters(Virginia Commonwealth University), Cynthia Shannon Weickert(Virginia Commonwealth University), Thomas W. Weickert(Virginia Commonwealth University), Myrna M. Weissman(Virginia Commonwealth University), Leanne M. Williams(Virginia Commonwealth University), Naomi R. Wray(Virginia Commonwealth University), Clement C. Zai(Virginia Commonwealth University), Esben Agerbo(Virginia Commonwealth University), Anders D. Børglum(Virginia Commonwealth University), Gerome Breen(Virginia Commonwealth University), Ditte Demontis(Virginia Commonwealth University), Annette Erlangsen(Virginia Commonwealth University), Joel Gelernter(Virginia Commonwealth University), Stephen J. Glatt(Virginia Commonwealth University), David M. Hougaard(Virginia Commonwealth University), Hai‐Gwo Hwu(Virginia Commonwealth University), Po‐Hsiu Kuo(Virginia Commonwealth University), Cathryn M. Lewis(Virginia Commonwealth University), Qingqin S. Li(Virginia Commonwealth University), Chih‐Min Liu(Virginia Commonwealth University), Nicholas G. Martin(Virginia Commonwealth University), Andrew M. McIntosh(Virginia Commonwealth University), Sarah E. Medland(Virginia Commonwealth University), Ole Mors(Virginia Commonwealth University), Merete Nordentoft(Virginia Commonwealth University), Catherine M. Olsen(Virginia Commonwealth University), David J. Porteous(Virginia Commonwealth University), Daniel J. Smıth(Virginia Commonwealth University), Eli A. Stahl(Virginia Commonwealth University), Murray B. Stein(Virginia Commonwealth University), Danuta Wasserman(Virginia Commonwealth University), Thomas Werge(Virginia Commonwealth University), David C. Whiteman(Virginia Commonwealth University), Virginia L. Willour(Virginia Commonwealth University), VA Million Veteran Program (MVP)(Virginia Commonwealth University), MVP Suicide Exemplar Workgroup(Virginia Commonwealth University), Hilary Coon(Virginia Commonwealth University), Jean C. Beckham(Virginia Commonwealth University), Nathan A. Kimbrel(Virginia Commonwealth University), Douglas M. Ruderfer(Virginia Commonwealth University)
American Journal of Psychiatry
October 1, 2023
10.1176/appi.ajp.21121266
Cited by 145Open Access
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Abstract

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: ). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

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