Dataset Information

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

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Mullins N

PROVIDER: S-EPMC8851871 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

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

Biological psychiatry 20210909 3

<h4>Background</h4>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.<h4>Methods</h4>We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortiu ...[more]

PMID: 34861974

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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