Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors
Authors: Mullins Niamh , Kang Jooeun , Campos Adrian I , Coleman Jonathan R I , Edwards Alexis C , Galfalvy Hanga , Levey Daniel F , Lori Adriana , Shabalin Andrey , Starnawska Anna , Su Mei-Hsin , Watson Hunna J , Adams Mark , Awasthi Swapnil , Gandal Michael , Hafferty Jonathan D , Hishimoto Akitoyo , Kim Minsoo , Okazaki Satoshi , Otsuka Ikuo , Ripke Stephan , Ware Erin B , Bergen Andrew W , Berrettini Wade H , Bohus Martin , Brandt Harry , Chang Xiao , Chen Wei J , Chen Hsi-Chung , Crawford Steven , Crow Scott , DiBlasi Emily , Duriez Philibert , Fernández-Aranda Fernando , Fichter Manfred M , Gallinger Steven , Glatt Stephen J , Gorwood Philip , Guo Yiran , Hakonarson Hakon , Halmi Katherine A , Hwu Hai-Gwo , Jain Sonia , Jamain Stéphane , Jiménez-Murcia Susana , Johnson Craig , Kaplan Allan S , Kaye Walter H , Keel Pamela K , Kennedy James L , Klump Kelly L , Levitan Robert D , Li Dong , Liao Shih-Cheng , Lieb Klaus , Lilenfeld Lisa , Liu Chih-Min , Magistretti Pierre J , Marshall Christian R , Mitchell James E , Monson Eric T , Myers Richard M , Pinto Dalila , Powers Abigail , Ramoz Nicolas , Roepke Stefan , Rotondo Alessandro , Rozanov Vsevolod , Scherer Stephen W , Schmahl Christian , Sokolowski Marcus , Strober Michael , Thornton Laura M , Treasure Janet , Tsuang Ming T , Via Maria C La , Witt Stephanie H , Woodside D Blake , Yilmaz Zeynep , Zillich Lea , Adolfsson Rolf , Agartz Ingrid , Air Tracy M , Alda Martin , Alfredsson Lars , Andreassen Ole A , Anjorin Adebayo , Appadurai Vivek , Artigas María Soler , Van der Auwera Sandra , Azevedo M Helena , Bass Nicholas , Bau Claiton HD , Baune Bernhard T , Bellivier Frank , Berger Klaus , Biernacka Joanna M , Bigdeli Tim B , Binder Elisabeth B , Boehnke Michael , Boks Marco , Bosch Rosa , Braff David L , Bryant Richard , Budde Monika , Byrne Enda M , Cahn Wiepke , Casas Miguel , Castelao Enrique , Cervilla Jorge A , Chaumette Boris , Cichon Sven , Corvin Aiden , Craddock Nicholas , Craig David , Degenhardt Franziska , Djurovic Srdjan , Edenberg Howard J , Fanous Ayman H , Foo Jerome C , Forstner Andreas J , Frye Mark , Fullerton Janice M , Gatt Justine M , Gejman Pablo V , Giegling Ina , Grabe Hans J , Green Melissa J , Grevet Eugenio H , Grigoroiu-Serbanescu Maria , Gutierrez Blanca , Guzman-Parra Jose , Hamilton Steven P , Hamshere Marian L , Hartmann Annette , Hauser Joanna , Heilmann-Heimbach Stefanie , Hoffmann Per , Ising Marcus , Jones Ian , Jones Lisa A , Jonsson Lina , Kahn René S , Kelsoe John R , Kendler Kenneth S , Kloiber Stefan , Koenen Karestan C , Kogevinas Manolis , Konte Bettina , Krebs Marie-Odile , Landén Mikael , Lawrence Jacob , Leboyer Marion , Lee Phil H , Levinson Douglas F , Liao Calwing , Lissowska Jolanta , Lucae Susanne , Mayoral Fermin , McElroy Susan L , McGrath Patrick , McGuffin Peter , McQuillin Andrew , Medland Sarah , Mehta Divya , Melle Ingrid , Milaneschi Yuri , Mitchell Philip B , Molina Esther , Morken Gunnar , Mortensen Preben Bo , Müller-Myhsok Bertram , Nievergelt Caroline , Nimgaonkar Vishwajit , Nöthen Markus M , O’Donovan Michael C , Ophoff Roel A , Owen Michael J , Pato Carlos , Pato Michele T , Penninx Brenda WJH , Pimm Jonathan , Pistis Giorgio , Potash James B , Power Robert A , Preisig Martin , Quested Digby , Ramos-Quiroga Josep Antoni , Reif Andreas , Ribasés Marta , Richarte Vanesa , Rietschel Marcella , Rivera Margarita , Roberts Andrea , Roberts Gloria , Rouleau Guy A , Rovaris Diego L , Rujescu Dan , Sánchez-Mora Cristina , Sanders Alan R , Schofield Peter R , Schulze Thomas G , Scott Laura J , Serretti Alessandro , Shi Jianxin , Shyn Stanley I , Sirignano Lea , Sklar Pamela , Smeland Olav B , Smoller Jordan W , Sonuga-Barke Edmund J S , Spalletta Gianfranco , Strauss John S , Świątkowska Beata , Trzaskowski Maciej , Turecki Gustavo , Vilar-Ribó Laura , Vincent John B , Völzke Henry , Walters James TR , Weickert Cynthia Shannon , Weickert Thomas W , Weissman Myrna M , Williams Leanne M ,   Major Depressive Disorder Working Group of the PsychiatricGenomics Consortium,   Bipolar Disorder Working Group of the Psychiatric Genomics Consortium,   Eating Disorders Working Group of the Psychiatric Genomics Consortium,   German Borderline Genomics Consortium, Wray Naomi R , Zai Clement , Agerbo Esben , Børglum Anders D , Breen Gerome , Erlangsen Annette , Esko Tõnu , Gelernter Joel , Hougaard David M , Kessler Ronald C , Kranzler Henry R , Li Qingqin S , Martin Nicholas G , McIntosh Andrew M , Medland Sarah E , Mors Ole , Nordentoft Merete , Olsen Catherine M , Porteous David , Ursano Robert J , Wasserman Danuta , Werge Thomas , Whiteman David C , Bulik Cynthia M , Coon Hilary , Demontis Ditte , Docherty Anna R , Kuo Po-Hsiu , Lewis Cathryn M , Mann J John , Rentería Miguel E , Smith Daniel J , Stahl Eli A , Stein Murray B , Streit Fabian , Willour Virginia , Ruderfer Douglas M 
Published: December 2020

Suicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a 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 and conditioned the results on psychiatric disorders using GWAS summary statistics, to investigate their shared and divergent genetic architectures. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated after conditioning and has previously been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, lower socioeconomic status, pain, lower educational attainment, reproductive traits, risk-taking, sleep disturbances, and poorer overall general health. After conditioning, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.