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

Mullins N, Kang JE, Campos AI, Coleman JR, Edwards AC, Galfalvy H, Levey DF, Lori A, Shabalin A, Starnawska A, Su MH, Watson HJ, Adams M, Awasthi S, Hafferty JD, Hishimoto A, Kim M, Okazaki S, Otsuka I, Ripke S, Ware EB, Bergen AW, Berrettini WH, Bohus M, Brandt H, Chang X, Chen WJ, Chen HC, Crawford S, Crow S, DiBlasi E, Duriez P, Fernández-Aranda F, Fichter MM, Gallinger S, Glatt SJ, Gorwood P, Guo Y, Hakonarson H, Halmi KA, Hwu HG, Jain S, Jamain S, Jiménez-Murcia S, Johnson C, Kaplan AS, Kaye WH, Keel PK, Kennedy JL, Klump KL, Li D, Liao SC, Lieb K, Lilenfeld L, Liu CM, Magistretti PJ, Marshall CR, Mitchell JE, Monson ET, Myers RM, Pinto D, Powers A, Ramoz N, Roepke S, Rozanov V, Scherer SW, Schmahl C, Sokolowski M, Strober M, Thornton LM, Treasure J, Tsuang MT, Witt SH, Woodside DB, Yilmaz Z, Zillich L, Adolfsson R, Agartz I, Air TM, Alda M, Alfredsson L, Andreassen OA, Anjorin A, Appadurai V, Soler Artigas M, Van der Auwera S, Azevedo MH, Bass N, Bau CH, Baune BT, Bellivier F, Berger K, Biernacka JM, Bigdeli TB, Binder EB, Boehnke M, Boks MP, Bosch R, Braff DL, Bryant R, Budde M, Byrne EM, Cahn W, Casas M, Castelao E, Cervilla JA, Chaumette B, Cichon S, Corvin A, Craddock N, Craig D, Degenhardt F, Djurovic S, Edenberg HJ, Fanous AH, Foo JC, Forstner AJ, Frye M, Fullerton JM, Gatt JM, Gejman PV, Giegling I, Grabe HJ, Green MJ, Grevet EH, Grigoroiu-Serbanescu M, Gutierrez B, Hamilton SP, Hamshere ML, Hartmann A, Hauser J, Heilmann-Heimbach S, Hoffmann P, Ising M, Jones I, Jones LA, Jonsson L, Kahn RS, Kelsoe JR, Kendler KS, Kloiber S, Koenen KC, Kogevinas M, Konte B, Krebs MO, Landén M, Lawrence J, Leboyer M, Lee PH, Levinson DF, Liao C, Lissowska J, Lucae S, Mayoral F, McElroy SL, McGrath P, McGuffin P, McQuillin A, Medland SE, Mehta D, Melle I, Milaneschi Y, Mitchell PB, Molina E, Morken G, Mortensen PB, Müller-Myhsok B, Nimgaonkar V, Nöthen MM, O'Donovan MC, Ophoff RA, Owen MJ, Pato C, Pato MT, Penninx BW, Pimm J, Pistis G, Potash JB, Power RA, Preisig M, Quested D, Ramos-Quiroga JA, Reif A, Ribasés M, Richarte V, Rietschel M, Rivera M, Roberts A, Roberts G, Rouleau GA, Rovaris DL, Rujescu D, Sánchez-Mora C, Sanders AR, Schofield PR, Schulze TG, Scott LJ, Serretti A, Shi J, Shyn SI, Sirignano L, Sklar P, Smeland OB, Smoller JW, Sonuga-Barke EJ, Spalletta G, Strauss JS, Świątkowska B, Trzaskowski M, Turecki G, Vilar-Ribó L, Vincent JB, Völzke H, Walters JT, Shannon Weickert C, Weickert TW, Weissman MM, Williams LM, Wray NR, Zai CC, Ashley-Koch AE, Hauser ER, Hauser MA, Kimbrel NA, Lindquist JH, McMahon B, Oslin DW, Qin X, Mattheisen M, Abdellaoui A, Adams MJ, Agerbo E, Andlauer TF, Bacanu SA, Bækvad-Hansen M, Beekman AT, Bryois J, Buttenschøn HN, Bybjerg-Grauholm J, Cai N, Christensen JH, Clarke TK, Colodro-Conde L, Couvy-Duchesne B, Crawford GE, Davies G, Derks EM, Direk N, Dolan CV, Dunn EC, Eley TC, Escott-Price V, Hassan Kiadeh FF, Finucane HK, Frank J, Gaspar HA, Gill M, Goes FS, Gordon SD, Weinsheimer SM, Wellmann J, Willemsen G, Wu Y, Xi HS, Yang J, Zhang F, Arolt V, Boomsma DI, Dannlowski U, de Geus EJ, DePaulo JR, Domenici E, Domschke K, Esko T, Grove J, Hall LS, Hansen CS, Hansen TF, Herms S, Hickie IB, Homuth G, Horn C, Hottenga JJ, Hougaard DM, Howard DM, Jansen R, Jorgenson E, Knowles JA, Kohane IS, Kraft J, Kretzschmar WW, Kutalik Z, Li Y, Lind PA, MacIntyre DJ, MacKinnon DF, Maier RM, Maier W, Marchini J, Mbarek H, Middeldorp CM, Mihailov E, Milani L, Mondimore FM, Montgomery GW, Mostafavi S, Nauck M, Ng B, Nivard MG, Nyholt DR, O'Reilly PF, Oskarsson H, Hayward C, Heath AC, Lewis G, Li QS, Madden PA, Magnusson PK, Martin NG, McIntosh AM, Metspalu A, Mors O, Nordentoft M, Paciga SA, Pedersen NL, Painter JN, Pedersen CB, Pedersen MG, Peterson RE, Peyrot WJ, Posthuma D, Quiroz JA, Qvist P, Rice JP, Riley BP, Mirza SS, Schoevers R, Schulte EC, Shen L, Sigurdsson E, Sinnamon GC, Smit JH, Smith DJ, Stefansson H, Steinberg S, Streit F, Strohmaier J, Tansey KE, Teismann H, Teumer A, Thompson W, Thomson PA, Thorgeirsson TE, Traylor M, Treutlein J, Trubetskoy V, Uitterlinden AG, Umbricht D, der Auwera SV, van Hemert AM, Viktorin A, Visscher PM, Wang Y, Webb BT, Perlis RH, Porteous DJ, Schaefer C, Stefansson K, Tiemeier H, Uher R, Werge T, Lewis CM, Breen G, Børglum AD, Sullivan PF, O'Connell KS, Coombes B, Qiao Z, Als TD, Børte S, Charney AW, Drange OK, Gandal MJ, Hagenaars SP, Ikeda M, Kamitaki N, Krebs K, Panagiotaropoulou G, Schilder BM, Sloofman LG, Winsvold BS, Won HH, Abramova L, Adorjan K, Al Eissa M, Albani D, Alliey-Rodriguez N, Antilla V, Antoniou A, Baek JH, Bauer M, Beins EC, Bergen SE, Birner A, Bøen E, Brum M, Brumpton BM, Brunkhorst-Kanaan N, Byerley W, Cairns M, Cervantes P, Cruceanu C, Cuellar-Barboza A, Cunningham J, Curtis D, Czerski PM, Dale AM, Dalkner N, David FS, Dobbyn AL, Douzenis A, Elvsåshagen T, Ferrier IN, Fiorentino A, Foroud TM, Forty L, Frei O, Freimer NB, Frisén L, Gade K, Garnham J, Gelernter J, Gizer IR, Gordon-Smith K, Greenwood TA, Guzman-Parra J, Ha K, Haraldsson M, Hautzinger M, Heilbronner U, Hellgren D, Holmans PA, Johnson JS, Kalman JL, Kamatani Y, Kittel-Schneider S, Koromina M, Kranz TM, Kranzler HR, Kubo M, Kupka R, Kushner SA, Lavebratt C, Leber M, Lee HJ, Levy SE, Lewis C, Lundberg M, Magnusson SH, Maihofer A, Malaspina D, Maratou E, Martinsson L, McGregor NW, McKay JD, Medeiros H, Millischer V, Moran JL, Morris DW, Mühleisen TW, O'Brien N, O'Donovan C, Olde Loohuis LM, Oruc L, Papiol S, Pardiñas AF, Perry A, Pfennig A, Porichi E, Raj T, Rapaport MH, Regeer EJ, Rivas F, Roth J, Roussos P, Ruderfer DM, Senner F, Sharp S, Shilling PD, Slaney C, Sobell JL, Artigas MS, Spijker AT, Stein DJ, Terao C, Toma C, Tooney P, Tsermpini EE, Vawter MP, Vedder H, Xi S, Xu W, Kay Yang JM, Young AH, Young H, Zandi PP, Zhou H, HUNT All-In Psychiatry , Babadjanova G, Backlund L, Bengesser S, Blackwood DH, Carr VJ, Catts S, Dikeos D, Etain B, Ferentinos P, Gawlik M, Gershon ES, Henskens F, Hillert J, Hong KS, Hultman CM, Hveem K, Iwata N, Jablensky AV, Kirov G, Lochner C, Loughland C, Mathews CA, McMahon FJ, Michie P, Mowry B, Neale BM, Nievergelt CM, Oedegaard KJ, Olsson T, Pantelis C, Patrinos GP, Reininghaus EZ, Saito T, Schall U, Schalling M, Scott RJ, Stordal E, Vaaler AE, Vieta E, Waldman ID, Zwart JA, Nurnberger JI, Stahl EA, Di Florio A, Adan RA, Ando T, Aschauer H, Baker JH, Bencko V, Birgegård A, Boden JM, Boehm I, Boni C, Perica VB, Buehren K, Bulik CM, Burghardt R, Carlberg L, Cassina M, Clementi M, Cone RD, Courtet P, Crowley JJ, Danner UN, Davis OS, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dina C, Dmitrzak-Weglarz M, Martinez ED, Duncan LE, Egberts K, Mattingsdal M, McDevitt S, Meulenbelt I, Micali N, Mitchell J, Mitchell K, Monteleone P, Monteleone AM, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, Olsen CM, O'Toole JK, Padyukov L, Palotie A, Pantel J, Papezova H, Parker R, Pearson JF, Ehrlich S, Escaramís G, Espeseth T, Estivill X, Farmer A, Favaro A, Fischer K, Floyd JA, Föcker M, Foretova L, Forzan M, Franklin CS, Gambaro G, Giuranna J, Giusti-Rodríquez P, Gonidakis F, Gordon S, Mayora MG, Guillaume S, Hanscombe KB, Hatzikotoulas K, Hebebrand J, Helder SG, Henders AK, Herpertz-Dahlmann B, Herzog W, Hinney A, Horwood LJ, Hübel C, Petersen LV, Purves KL, Raevuori A, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rybakowski F, Santonastaso P, Scherag A, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op ‘t Landt MC, Slopien A, Soranzo N, Sorbi S, Southam L, Steen VW, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jordan J, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJ, Kennedy MA, Keski-Rahkonen A, Kiezebrink K, Kim YR, Kirk KM, Klareskog L, Knudsen GPS, Larsen JT, Le Hellard S, Leppä VM, Lichtenstein P, Lin BD, Lundervold A, Luykx J, Maj M, Mannik K, Marsal S, Stuber GD, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wade TD, Wagner G, Walton E, Whiteman DC, Wichmann HE, Widen E, Yao S, Zeggini E, Zerwas S, Zipfel S, Jungkunz M, Dietl L, Schwarze CE, Dahmen N, Schott BH, Mobascher A, Crivelli S, Dennis MF, Harvey PD, Carter BW, Huffman JE, Jacobson D, Madduri R, Olsen MK, Pestian J, Gaziano JM, Muralidhar S, Ramoni R, Beckham J, Chang KM, O'Donnell CJ, Tsao PS, Breeling J, Huang G, Romero JP, Moser J, Whitbourne SB, Brewer JV, Aslan M, Connor T, Argyres DP, Stephens B, Brophy MT, Humphries DE, Selva LE, Do N, Shayan S, Cho K, Pyarajan S, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Mattocks K, Harley J, Zablocki CJ, Whittle J, Jacono F, Gutierrez S, Gibson G, Hammer K, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Mathew R, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Ivins D, Mastorides S, Moorman J, Gappy S, Klein J, Ratcliffe N, Florez H, Okusaga O, Murdoch M, Sriram P, Yeh SS, Tandon N, Jhala D, Aguayo S, Cohen D, Sharma S, Liangpunsakul S, Oursler KA, Whooley M, Ahuja S, Constans J, Meyer P, Greco J, Rauchman M, Servatius R, Gaddy M, Wallbom A, Morgan T, Stapley T, Sherman S, Ross G, Strollo P, Boyko E, Meyer L, Gupta S, Huq M, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R, Erlangsen A, Kessler RC, Ursano RJ, Wasserman D, Coon H, Demontis D, Docherty AR, Kuo PH, Mann JJ, Rentería ME, Stein MB, Willour V (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 91

Pages Range: 313-327

Journal Issue: 3

DOI: 10.1016/j.biopsych.2021.05.029

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.

Involved external institutions

Aarhus University Denmark (DK) Harvard University United States (USA) (US) Uniformed Services University United States (USA) (US) Karolinska Institute Sweden (SE) University of Utah United States (USA) (US) Duke University Medical Center United States (USA) (US) University of North Carolina at Chapel Hill United States (USA) (US) Virginia Commonwealth University (VCU) United States (USA) (US) National Taiwan University (NTU) Taiwan (TW) Columbia University United States (USA) (US) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) University of California, San Diego (UC San Diego, UCSD) United States (USA) (US) University of Iowa United States (USA) (US) Icahn School of Medicine at Mount Sinai United States (USA) (US) VA Connecticut Healthcare System United States (USA) (US) University of Pennsylvania (UPenn) United States (USA) (US) Vanderbilt University United States (USA) (US) NTNU Trondheim - Norwegian University of Science and Technology Norway (NO) Universidade de Coimbra Portugal (PT) University College London (UCL) United Kingdom (GB) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) Hospital de Clínicas de Porto Alegre (HCPA) Brazil (BR) Assistance Publique-Hôpitaux de Paris (AP-HP) France (FR) Westfälische Wilhelms-Universität (WWU) Münster Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) Germany (DE) University of Edinburgh United Kingdom (GB) Forschungszentrum Jülich / Research Centre Jülich (FZJ) Germany (DE) Mayo Clinic United States (USA) (US) University of New South Wales (UNSW) Australia (AU) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron Spain (ES) Lausanne University Hospital / Centre hospitalier universitaire vaudois (CHUV) Switzerland (CH) Complejo Hospitalario Universitario de Granada Spain (ES) University of Glasgow United Kingdom (GB) Indiana University United States (USA) (US) SUNY Downstate Medical Center United States (USA) (US) The Jane and Terry Semel Institute for Neuroscience and Human Behavior United States (USA) (US) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US) King’s College London United Kingdom (GB) Instituto de Salud Global de Barcelona (ISGlobal) Spain (ES) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) National Center for Scientific Research / Centre national de la recherche scientifique (CNRS) France (FR) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) Klinikum der Universität München (LMU Klinikum) Germany (DE) University of Queensland Australia (AU) Janssen Global Services, LLC United States (USA) (US) Trinity College Dublin Ireland (IE) Lundbeck Foundation Initiative for Integrative Psychiatric Research Denmark (DK) Charité - Universitätsmedizin Berlin Germany (DE) University of Pittsburgh United States (USA) (US) University of Michigan United States (USA) (US) Universitätsklinikum Bonn Germany (DE) BioRealm, LLC. United States (USA) (US) NIHR Maudsley Biomedical Research Centre United Kingdom (GB) Sheppard Pratt United States (USA) (US) Children's Hospital of Philadelphia United States (USA) (US) National Taiwan University Hospital (NTUH) / 國立台灣大學醫學院附設醫院 Taiwan (TW) Emory University United States (USA) (US) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) University of Minnesota (UMN) United States (USA) (US) Bellvitge University Hospital / Hospital Universitari de Bellvitge Spain (ES) University of Western Australia (UWA) Australia (AU) University of Toronto Canada (CA) State University of New York Upstate Medical University (SUNY) United States (USA) (US) Centre hospitalier Sainte-Anne France (FR) Weill Cornell Medicine United States (USA) (US) Florida State University (FSU) United States (USA) (US) Harvard T.H. Chan School of Public Health United States (USA) (US) Institut Mondor de Recherche Biomédicale France (FR) McGill University Canada (CA) Eating Recovery Center United States (USA) (US) University of São Paulo / Universidade de São Paulo (USP) Brazil (BR) Michigan State University United States (USA) (US) Ludwig-Maximilians-Universität (LMU) Germany (DE) Universidad de Granada Spain (ES) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) The Chicago School United States (USA) (US) Kaiser Permanente United States (USA) (US) Cardiff University United Kingdom (GB) NorthShore University HealthSystem United States (USA) (US) King Abdullah University of Science and Technology (KAUST) / جامعة الملك عبد الله للعلوم و التقنية Saudi Arabia (SA) Poznan University of Medical Sciences / Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu Poland (PL) The Hospital for Sick Children (SickKids) Canada (CA) University of North Dakota United States (USA) (US) HudsonAlpha United States (USA) (US) Universitätsspital Basel Switzerland (CH) Centre for Addiction and Mental Health (CAMH) Canada (CA) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) France (FR) Saint Petersburg State University (SPbU) / Санкт-Петербургский государственный университет (СПбГУ) Russian Federation (RU) University Of Worcester United Kingdom (GB) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) University of Gothenburg / Göteborgs universitet Sweden (SE) North East London NHS Foundation Trust United Kingdom (GB) Stanford University United States (USA) (US) Dalhousie University Canada (CA) Université Paris Cité France (FR) University of Southern California (USC) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Lindner Center of HOPE United States (USA) (US) Vrije Universiteit Amsterdam (VU) / University Amsterdam Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) University of Oxford United Kingdom (GB) Umeå University Sweden (SE) University of Bologna / Università di Bologna Italy (IT) National Cancer Institute (NCI) United States (USA) (US) University of Adelaide Australia (AU) Baylor College of Medicine United States (USA) (US) Berkshire Healthcare NHS Foundation Trust United Kingdom (GB) Nofer Institute of Occupational Medicine (NIOM) Poland (PL) Institute of Biological Psychiatry Denmark (DK) Durham VA Medical Center United States (USA) (US) Los Alamos National Laboratory United States (USA) (US)

How to cite

APA:

Mullins, N., Kang, J.E., Campos, A.I., Coleman, J.R., Edwards, A.C., Galfalvy, H.,... Willour, V. (2022). Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors. Biological Psychiatry, 91(3), 313-327. https://doi.org/10.1016/j.biopsych.2021.05.029

MLA:

Mullins, Niamh, et al. "Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors." Biological Psychiatry 91.3 (2022): 313-327.

BibTeX: Download