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.
| Original language | English |
|---|---|
| Pages (from-to) | 313-327 |
| Number of pages | 15 |
| Journal | Biological Psychiatry |
| Volume | 91 |
| Issue number | 3 |
| DOIs | |
| State | Published - Feb 1 2022 |
Funding
Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM]). The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding body. We thank the participants who donated their time, life experiences, and DNA to this research, and the clinical and scientific teams that worked with them. The International Suicide Genetics Consortium has made genome-wide summary results from this study available online (https://tinyurl.com/ISGC2021). This study included some publicly available datasets accessed through dbGaP (Psychiatric Genomics Consortium [PGC] bundle phs001254) and the Haplotype Reference Consortium reference panel v.1.0 (http://www.haplotype-reference-consortium.org/home). Databases used: Open Targets Genetics web portal (https://genetics.opentargets.org), LDHub (http://ldsc.broadinstitute.org), and FUMA (https://fuma.ctglab.nl). In the past 3 years, RCK was a consultant for Datastat, Inc. Sage Pharmaceuticals, and Takeda. HRK and JG are named as inventors on PCT patent application #15/878,640 entitled: ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. HRK is a member of an advisory board for Dicerna Pharmaceuticals and of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which was supported in the last 3 years by AbbVie, Alkermes, Dicerna, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka, Pfizer, Arbor, and Amygdala Neurosciences. DL is an employee of Janssen Research & Development, LLC, and shareholder in Johnson & Johnson, the parent company of the Janssen companies. DL declares that, except for income received from her primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. MBS has in the past 3 years been a consultant for Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Epivario, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Oxeia Biopharmaceuticals. MBS has stock options in Oxeia Biopharmaceuticals and Epivario. HJG has received travel grants and speaker honoraria from Fresenius Medical Care, Neuraxpharm, Servier, and Janssen-Cilag as well as research funding from Fresenius Medical Care. OAA is a consultant for HealthLytix and received speaker's honorarium from Lundbeck and Sunovion. RAP is employed by and holds shares in BioMarin Pharmaceuticals. MCO and MJO are supported by a collaborative research grant from Takeda Pharmaceuticals. That support did not contribute to the work described in this manuscript. EHG has served in the speakers? bureau and the advisory board of Takeda (former Shire do Brasil) Pharmaceutical. JAR-Q was on the speakers? bureau and/or acted as consultant for Eli Lilly, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogui, Lundbeck, Almirall, Braingaze, Sincrolab, Medice, and Rubi? in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubi?, Shire, Takeda, Shionogui, Bial, Medice, and Eli Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli Lilly, Lundbeck, Janssen-Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubi?. VR was on the speakers? bureau and/or acted as consultant for Takeda and Rubi? in the last 5 years. She also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Rubi?, Shire, Takeda, and Lundbeck. MC was on the speakers? bureau and/or acted as consultant for Janssen-Cilag in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag. All other authors report no biomedical financial interests or potential conflicts of interest. Full acknowledgments are available in Supplement 1. Naomi R. Wray?,1,2, Stephan Ripke?,3,4,5, Manuel Mattheisen?,6,7,8, Maciej Trzaskowski1, Enda M. Byrne1, Abdel Abdellaoui9, Mark J. Adams10, Esben Agerbo11,12,13, Tracy M. Air14, Till F.M. Andlauer15,16, Silviu-Alin Bacanu17, Marie B?kvad-Hansen13,18, Aartjan T.F. Beekman19, Tim B. Bigdeli17,20, Elisabeth B. Binder15,21, Julien Bryois22, Henriette N. Buttensch?n13,23,24, Jonas Bybjerg-Grauholm13,18, Na Cai25,26, Enrique Castelao27, Jane Hvarregaard Christensen8,13,24, Toni-Kim Clarke10, Jonathan R.I. Coleman28, Luc?a Colodro-Conde29, Baptiste Couvy-Duchesne2,30, Nick Craddock31, Gregory E. Crawford32,33, Gail Davies34, Franziska Degenhardt35, Eske M. Derks29, Nese Direk36,37, Conor V. Dolan9, Erin C. Dunn38,39,40, Thalia C. Eley28, Valentina Escott-Price41, Farnush Farhadi Hassan Kiadeh42, Hilary K. Finucane43,44, Jerome C. Foo45, Andreas J. Forstner35,46,47,48, Josef Frank45, H?l?na A. Gaspar28, Michael Gill49, Fernando S. Goes50, Scott D. Gordon29, Shantel Marie Weinsheimer13,54, J?rgen Wellmann101, Gonneke Willemsen9, Stephanie H. Witt45, Yang Wu1, Hualin S. Xi112, Jian Yang2,113, Futao Zhang1, Volker Arolt114, Bernhard T. Baune114,115,116, Klaus Berger101, Dorret I. Boomsma9, Sven Cichon35,47,117,118, Udo Dannlowski114, E.J.C. de Geus9,119, J. Raymond Depaulo50, Enrico Domenici120, Katharina Domschke121,122, T?nu Esko5,78, Hans J. Grabe109, Steven P. Hamilton123, Jakob Grove8,13,24,51, Lynsey S. Hall10,52, Christine S?holm Hansen13,18, Thomas F. Hansen53,54,55, Stefan Herms35,47, Ian B. Hickie56, Per Hoffmann35,47, Georg Homuth57, Carsten Horn58, Jouke-Jan Hottenga9, David M. Hougaard13,18, David M. Howard10,28, Marcus Ising59, Rick Jansen19, Ian Jones60, Lisa A. Jones61, Eric Jorgenson62, James A. Knowles63, Isaac S. Kohane64,65,66, Julia Kraft4, Warren W. Kretzschmar67, Zolt?n Kutalik68,69, Yihan Li67, Penelope A. Lind29, Donald J. MacIntyre70,71, Dean F. MacKinnon50, Robert M. Maier2, Wolfgang Maier72, Jonathan Marchini73, Hamdi Mbarek9, Patrick McGrath74, Peter McGuffin28, Sarah E. Medland29, Divya Mehta2,75, Christel M. Middeldorp9,76,77, Evelin Mihailov78, Yuri Milaneschi19, Lili Milani78, Francis M. Mondimore50, Grant W. Montgomery1, Sara Mostafavi79, 80, Niamh Mullins28, Matthias Nauck81,82, Bernard Ng80, Michel G. Nivard9, Dale R. Nyholt83, Paul F. O'Reilly28, Hogni Oskarsson84, Caroline Hayward124, Andrew C. Heath89, Kenneth S. Kendler17, Stefan Kloiber59,125,126, Glyn Lewis127, Qingqin S. Li128, Susanne Lucae59, Pamela A.F. Madden89, Patrik K. Magnusson22, Nicholas G. Martin29, Andrew M. McIntosh10,34, Andres Metspalu78,129, Ole Mors13,130, Preben Bo Mortensen11,12,13,24, Bertram M?ller-Myhsok15,131,132, Merete Nordentoft13,133, Markus M. N?then35, Michael C. O'Donovan60, Sara A. Paciga134, Nancy L. Pedersen22, Michael J. Owen60, Jodie N. Painter29, Carsten B?cker Pedersen11,12,13, Marianne Gi?rtz Pedersen11,12,13, Roseann E. Peterson17,85, Wouter J. Peyrot19, Giorgio Pistis27, Danielle Posthuma86,87, Jorge A. Quiroz88, Per Qvist8,13,24, John P. Rice89, Brien P. Riley17, Margarita Rivera28,90, Saira Saeed Mirza36, Robert Schoevers91, Eva C. Schulte92,93, Ling Shen62, Jianxin Shi94, Stanley I. Shyn95, Engilbert Sigurdsson96, Grant C.B. Sinnamon97, Johannes H. Smit19, Daniel J. Smith98, Hreinn Stefansson99, Stacy Steinberg99, Fabian Streit45, Jana Strohmaier45, Katherine E. Tansey100, Henning Teismann101, Alexander Teumer102, Wesley Thompson13,54,103,104, Pippa A. Thomson105, Thorgeir E. Thorgeirsson99, Matthew Traylor106, Jens Treutlein45, Vassily Trubetskoy4, Andr? G. Uitterlinden107, Daniel Umbricht108, Sandra Van der Auwera109, Albert M. van Hemert110, Alexander Viktorin22, Peter M. Visscher1,2, Yunpeng Wang13,54,104, Bradley T. Webb111, Brenda W.J.H. Penninx19, Roy H. Perlis38,135, David J. Porteous105, James B. Potash136, Martin Preisig27, Marcella Rietschel45, Catherine Schaefer62, Thomas G. Schulze45,93,137,138,139, Jordan W. Smoller38,39,40, Kari Stefansson99,140, Henning Tiemeier36,141,142, Rudolf Uher143, Henry V?lzke102, Myrna M. Weissman74,144, Thomas Werge13,54,145, Cathryn M. Lewis?,28,146, Douglas F. Levinson?,147, Gerome Breen?,28,148, Anders D. B?rglum?,8,13,24, and Patrick F. Sullivan?,22,149,150 Niamh Mullins1,2, Andreas J. Forstner3,4,5, Kevin S. O'Connell6,7, Brandon Coombes8, Jonathan R.I. Coleman9,10, Zhen Qiao11, Thomas D. Als12,13,14, Tim B. Bigdeli15,16, Sigrid B?rte17,18,19, Julien Bryois20, Alexander W. Charney2, Ole Kristian Drange21,22, Michael J. Gandal23, Saskia P. Hagenaars9,10, Masashi Ikeda24, Nolan Kamitaki25,26, Minsoo Kim23, Kristi Krebs27, Georgia Panagiotaropoulou28, Brian M. Schilder1,29,30,31, Laura G. Sloofman1, Stacy Steinberg32, Vassily Trubetskoy28, Bendik S. Winsvold19,33, Hong-Hee Won34, Liliya Abramova35, Kristina Adorjan36,37, Esben Agerbo14,38,39, Mariam Al Eissa40, Diego Albani41, Ney Alliey-Rodriguez42,43, Adebayo Anjorin44, Verneri Antilla45, Anastasia Antoniou46, Swapnil Awasthi28, Ji Hyun Baek47, Marie B?kvad-Hansen14,48, Nicholas Bass40, Michael Bauer49, Eva C. Beins3, Sarah E. Bergen20, Armin Birner50, Carsten B?cker Pedersen14,38,39, Erlend B?en51, Marco P. Boks52, Rosa Bosch53,54,55,56, Murielle Brum57, Ben M. Brumpton19, Nathalie Brunkhorst-Kanaan57, Monika Budde36, Jonas Bybjerg-Grauholm14,48, William Byerley58, Murray Cairns59, Miquel Casas53,54,55,56, Pablo Cervantes60, Toni-Kim Clarke61, Cristiana Cruceanu60,62, Alfredo Cuellar-Barboza63,64, Julie Cunningham65, David Curtis66,67, Piotr M. Czerski68, Anders M. Dale69, Nina Dalkner50, Friederike S. David3, Franziska Degenhardt3,70, Srdjan Djurovic71,72, Amanda L. Dobbyn1,2, Athanassios Douzenis46, Torbj?rn Elvs?shagen18,73,74, Valentina Escott-Price75, I. Nicol Ferrier76, Alessia Fiorentino40, Tatiana M. Foroud77, Liz Forty75, Josef Frank78, Oleksandr Frei6,18, Nelson B. Freimer23,79, Louise Fris?n80, Katrin Gade36,81, Julie Garnham82, Joel Gelernter83,84,85, Marianne Gi?rtz Pedersen14,38,39, Ian R. Gizer86, Scott D. Gordon87, Katherine Gordon-Smith88, Tiffany A. Greenwood89, Jakob Grove12,13,14,90, Jos? Guzman-Parra91, Kyooseob Ha92, Magnus Haraldsson93, Martin Hautzinger94, Urs Heilbronner36, Dennis Hellgren20, Stefan Herms3,95,96, Per Hoffmann3,95,96, Peter A. Holmans75, Laura Huckins1,2, St?phane Jamain97,98, Jessica S. Johnson1,2, Janos L. Kalman36,37,99, Yoichiro Kamatani100,101, James L. Kennedy102,103,104,105, Sarah Kittel-Schneider57,106, James A. Knowles107,108, Manolis Kogevinas109, Maria Koromina110, Thorsten M. Kranz57, Henry R. Kranzler111,112, Michiaki Kubo113, Ralph Kupka114,115,116, Steven A. Kushner117, Catharina Lavebratt118,119, Jacob Lawrence120, Markus Leber121, Heon-Jeong Lee122, Phil H. Lee123, Shawn E. Levy124, Catrin Lewis75, Calwing Liao125,126, Susanne Lucae62, Martin Lundberg118,119, Donald J. MacIntyre127, Sigurdur H. Magnusson32, Wolfgang Maier128, Adam Maihofer89, Dolores Malaspina1,2, Eirini Maratou129, Lina Martinsson80, Manuel Mattheisen12,13,14,106,130, Nathaniel W. McGregor131, Peter McGuffin9, James D. McKay132, Helena Medeiros108, Sarah E Medland87, Vincent Millischer118,119, Grant W. Montgomery11, Jennifer L. Moran25,133, Derek W. Morris134, Thomas W. M?hleisen4,95, Niamh O'Brien40, Claire O'Donovan82, Loes M. Olde Loohuis23,79, Lilijana Oruc135, Sergi Papiol36,37, Antonio F. Pardi?as75, Amy Perry88, Andrea Pfennig49, Evgenia Porichi46, James B. Potash136, Digby Quested137,138, Towfique Raj1,29,30,31, Mark H. Rapaport139, J. Raymond DePaulo136, Eline J. Regeer140, John P. Rice141, Fabio Rivas91, Margarita Rivera142,143, Julian Roth106, Panos Roussos1,2,29, Douglas M. Ruderfer144, Cristina S?nchez-Mora53,54,56,145, Eva C. Schulte36,37, Fanny Senner36,37, Sally Sharp40, Paul D. Shilling89, Engilbert Sigurdsson93,146, Lea Sirignano78, Claire Slaney82, Olav B. Smeland6,7, Daniel J. Smith147, Janet L. Sobell148, Christine S?holm Hansen14,48, Maria Soler Artigas53,54,56,145, Anne T. Spijker149, Dan J. Stein150, John S. Strauss102, Beata ?wi?tkowska151, Chikashi Terao101, Thorgeir E. Thorgeirsson32, Claudio Toma152,153,154, Paul Tooney59, Evangelia-Eirini Tsermpini110, Marquis P. Vawter155, Helmut Vedder156, James T.R. Walters75, Stephanie H. Witt78, Simon Xi157, Wei Xu158, Jessica Mei Kay Yang75, Allan H. Young159,160, Hannah Young1, Peter P. Zandi136, Hang Zhou83,84, Lea Zillich78, HUNT All-In Psychiatry161, Rolf Adolfsson162, Ingrid Agartz51,130,163, Martin Alda82,164, Lars Alfredsson165, Gulja Babadjanova166, Lena Backlund118,119, Bernhard T. Baune167,168,169, Frank Bellivier170,171, Susanne Bengesser50, Wade H. Berrettini172, Douglas H.R. Blackwood61, Michael Boehnke173, Anders D. B?rglum14,174,175, Gerome Breen9,10, Vaughan J. Carr176, Stanley Catts177, Aiden Corvin178, Nicholas Craddock75, Udo Dannlowski167, Dimitris Dikeos179, T?nu Esko26,27,180,181, Bruno Etain170,171, Panagiotis Ferentinos9,46, Mark Frye64, Janice M. Fullerton152,153, Micha Gawlik106, Elliot S. Gershon42,182, Fernando S. Goes136, Melissa J. Green152,176, Maria Grigoroiu-Serbanescu183, Joanna Hauser68, Frans Henskens59, Jan Hillert80, Kyung Sue Hong47, David M. Hougaard14,48, Christina M. Hultman20, Kristian Hveem19,184, Nakao Iwata24, Assen V. Jablensky185, Ian Jones75, Lisa A Jones88, Ren? S. Kahn2,52, John R. Kelsoe89, George Kirov75, Mikael Land?n20,186, Marion Leboyer97,98,187, Cathryn M. Lewis9,10,188, Qingqin S. Li189, Jolanta Lissowska190, Christine Lochner191, Carmel Loughland59, Nicholas G. Martin87,192, Carol A. Mathews193, Fermin Mayoral91, Susan L. McElroy194, Andrew M. McIntosh127,195, Francis J. McMahon196, Ingrid Melle6,197, Patricia Michie59, Lili Milani27, Philip B. Mitchell176, Gunnar Morken21,198, Ole Mors14,199, Preben Bo Mortensen12,14,38,39, Bryan Mowry177, Bertram M?ller-Myhsok62,200,201, Richard M. Myers124, Benjamin M. Neale25,45,180, Caroline M. Nievergelt89,202, Merete Nordentoft14,203, Markus M. N?then3, Michael C. O'Donovan75, Ketil J. Oedegaard204,205, Tomas Olsson206, Michael J. Owen75, Sara A. Paciga207, Chris Pantelis208, Carlos Pato108, Michele T. Pato108, George P. Patrinos110,209,210, Roy H. Perlis211,212, Danielle Posthuma213,214, Josep Antoni Ramos-Quiroga53,54,55,56, Andreas Reif57, Eva Z. Reininghaus50, Marta Ribas?s53,54,56,145, Marcella Rietschel78, Stephan Ripke25,28,45, Guy A. Rouleau126,215, Takeo Saito24, Ulrich Schall59, Martin Schalling118,119, Peter R. Schofield152,153, Thomas G. Schulze36,78,81,136,216, Laura J. Scott173, Rodney J. Scott59, Alessandro Serretti217, Cynthia Shannon Weickert152,176,218, Jordan W. Smoller25,133,219, Hreinn Stefansson32, Kari Stefansson32,220, Eystein Stordal221,222, Fabian Streit78, Patrick F. Sullivan20,223,224, Gustavo Turecki225, Arne E. Vaaler226, Eduard Vieta227, John B. Vincent102, Irwin D. Waldman228, Thomas W. Weickert152,176,218, Thomas Werge14,229,230,231, Naomi R. Wray11,232, John-Anker Zwart18,19,33, Joanna M. Biernacka8,64, John I. Nurnberger233, Sven Cichon3,4,95,96, Howard J. Edenberg77,234, Eli A. Stahl1,2,180, Andrew McQuillin40, Arianna Di Florio75,224, Roel A. Ophoff23,79,117,235, and Ole A. Andreassen6,7 Roger A.H. Adan1,2,3, Lars Alfredsson4, Tetsuya Ando5, Ole A. Andreassen6, Harald Aschauer7, Jessica H. Baker8, Vladimir Bencko9, Andrew W. Bergen10,11, Wade H. Berrettini12, Andreas Birgeg?rd13,14,15, Joseph M. Boden16, Ilka Boehm17, Claudette Boni18, Vesna Boraska Perica19,20, Harry Brandt21, Gerome Breen22,23, Julien Bryois15, Katharina Buehren24, Cynthia M. Bulik8,15,25, Roland Burghardt26, Laura Carlberg27, Matteo Cassina28, Sven Cichon29,30,31, Maurizio Clementi28, Jonathan R.I. Coleman22,23, Roger D. Cone32, Philippe Courtet33, Steven Crawford21, Scott Crow34, James J. Crowley13,35, Unna N. Danner2, Oliver S.P. Davis36,37, Martina de Zwaan38, George Dedoussis39, Daniela Degortes40, Janiece E. DeSocio41, Danielle M. Dick42,43,44, Dimitris Dikeos45, Christian Dina46, Monika Dmitrzak-Weglarz47, Elisa Docampo Martinez48,49,50, Laramie E. Duncan51, Karin Egberts52, Christian R. Marshall126, Nicholas G. Martin72, Manuel Mattheisen13,14,75,127, Morten Mattingsdal6, Sara McDevitt128,129, Peter McGuffin22, Sarah E. Medland72, Andres Metspalu53,130, Ingrid Meulenbelt131, Nadia Micali132,133, James Mitchell134, Karen Mitchell135,136, Palmiero Monteleone137, Alessio Maria Monteleone124, Grant W. Montgomery72,86,138, Preben Bo Mortensen76,114,115, Melissa A. Munn-Chernoff8, Benedetta Nacmias139, Marie Navratilova63, Ioanna Ntalla39, Catherine M. Olsen140, Roel A. Ophoff141,142, Julie K. O'Toole143, Leonid Padyukov110, Aarno Palotie54,102,144, Jacques Pantel18, Hana Papezova97, Richard Parker72, John F. Pearson145, Nancy L. Pedersen15, Stefan Ehrlich17, Ge?rgia Escaram?s48,49,50, T?nu Esko53,54, Thomas Espeseth55, Xavier Estivill48,49,50,56, Anne Farmer22, Angela Favaro40, Fernando Fern?ndez-Aranda57,58, Manfred M. Fichter59,60, Krista Fischer53, James A.B. Floyd61, Manuel F?cker62, Lenka Foretova63, Andreas J. Forstner30,64,65,66, Monica Forzan28, Christopher S. Franklin19, Steven Gallinger67, Giovanni Gambaro68, H?l?na A. Gaspar22,23, Ina Giegling69, Johanna Giuranna70, Paola Giusti-Rodr?quez35, Fragiskos Gonidakis71, Scott Gordon72, Philip Gorwood73,74, Monica Gratacos Mayora48,49,50, Jakob Grove75,76,77,78, S?bastien Guillaume33, Yiran Guo79, Hakon Hakonarson79,80, Katherine A. Halmi81, Ken B. Hanscombe82, Konstantinos Hatzikotoulas19,83, Joanna Hauser84, Johannes Hebebrand70, Sietske G. Helder22,85, Anjali K. Henders86, Stefan Herms29,30, Beate Herpertz-Dahlmann24, Wolfgang Herzog87, Anke Hinney70, L. John Horwood16, Christopher H?bel15,22, Liselotte V. Petersen76,114,115, Dalila Pinto88, Kirstin L. Purves22, Anu Raevuori101, Nicolas Ramoz18, Ted Reichborn-Kjennerud112,146, Valdo Ricca147, Samuli Ripatti148, Stephan Ripke149,150,151, Franziska Ritschel17,152, Marion Roberts22, Dan Rujescu69, Filip Rybakowski154, Paolo Santonastaso155, Andr? Scherag156, Stephen W. Scherer157,158, Ulrike Schmidt22, Nicholas J. Schork159, Alexandra Schosser160, Jochen Seitz24, Lenka Slachtova161, P. Eline Slagboom131, Margarita C.T. Slof-Op ?t Landt162,163, Agnieszka Slopien164, Nicole Soranzo19,165,166,167, Sandro Sorbi139,168, Lorraine Southam19, Vidar W. Steen169,170, Michael Strober171,172, Laura M. Huckins88, James I. Hudson89, Hartmut Imgart90, Hidetoshi Inoko91, Vladimir Janout92, Susana Jim?nez-Murcia57,58, Craig Johnson93, Jennifer Jordan94,95, Antonio Juli?96, Gursharan Kalsi22, Deborah Kaminsk?97, Allan S. Kaplan98,99,100, Jaakko Kaprio101,102, Leila Karhunen103, Andreas Karwautz104, Martien J.H. Kas1,105, Walter H. Kaye106, James L. Kennedy98,99,100, Martin A. Kennedy107, Anna Keski-Rahkonen101, Kirsty Kiezebrink108, Youl-Ri Kim109, Katherine M. Kirk72, Lars Klareskog110, Kelly L. Klump111, Gun Peggy S. Knudsen112, Mikael Land?n15,113, Janne T. Larsen76,114,115, Stephanie Le Hellard116,117,118, Virpi M. Lepp?15, Dong Li79, Paul Lichtenstein15, Lisa Lilenfeld119, Bochao Danae Lin1, Jolanta Lissowska120, Astri Lundervold121, Jurjen Luykx1, Pierre J. Magistretti122,123, Mario Maj124, Katrin Mannik53,125, Sara Marsal96, Garret D. Stuber8,173, Patrick F. Sullivan8,15,35, Beata ?wi?tkowska174, Jin P. Szatkiewicz35, Ioanna Tachmazidou19, Elena Tenconi40, Laura M. Thornton8, Alfonso Tortorella175,176, Federica Tozzi177, Janet Treasure22, Artemis Tsitsika178, Marta Tyszkiewicz-Nwafor164, Konstantinos Tziouvas179, Annemarie A. van Elburg2,180, Eric F. van Furth162,163, Tracey D. Wade181, Gudrun Wagner104, Esther Walton17, Hunna J. Watson8,182,183, Thomas Werge184, David C. Whiteman140, H. Erich Wichmann185, Elisabeth Widen102, D. Blake Woodside99,100,186,187, Shuyang Yao15, Zeynep Yilmaz8,35, Eleftheria Zeggini19,83, Stephanie Zerwas8, and Stephan Zipfel188 J. Michael Gaziano, M.D., M.P.H. (co-chair, VA Boston Healthcare System), Sumitra Muralidhar, Ph.D. (co-chair, U.S. Department of Veterans Affairs), Rachel Ramoni, D.M.D., Sc.D. (U.S. Department of Veterans Affairs), Jean Beckham, Ph.D. (Durham VA Medical Center), Kyong-Mi Chang, M.D. (Philadelphia VA Medical Center), Christopher J. O'Donnell, M.D., M.P.H. (VA Boston Healthcare System), Philip S. Tsao, Ph.D. (VA Palo Alto Health Care System), James Breeling, M.D. (Ex-Officio, U.S. Department of Veterans Affairs), Grant Huang, Ph.D. (Ex-Officio, U.S. Department of Veterans Affairs), and J.P. Casas Romero, M.D., Ph.D. (Ex-Officio, VA Boston Healthcare System). MVP Program Office: Sumitra Muralidhar, Ph.D., and Jennifer Moser, Ph.D., both of U.S. Department of Veterans Affairs. MVP Recruitment/Enrollment: Recruitment/Enrollment Director/Deputy Director, Boston?Stacey B. Whitbourne, Ph.D., Jessica V. Brewer, M.P.H. (VA Boston Healthcare System). MVP Coordinating Centers: Clinical Epidemiology Research Center (CERC), West Haven?Mihaela Aslan, Ph.D. (West Haven VA Medical Center). Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque?Todd Connor, Pharm.D., Dean P. Argyres, B.S., M.S. (New Mexico VA Health Care System). Genomics Coordinating Center, Palo Alto?Philip S. Tsao, Ph.D. (VA Palo Alto Health Care System). MVP Boston Coordinating Center, Boston?J. Michael Gaziano, M.D., M.P.H. (VA Boston Healthcare System). MVP Information Center, Canandaigua?Brady Stephens, M.S. (Canandaigua VA Medical Center). VA Central Biorepository, Boston?Mary T. Brophy, M.D., M.P.H., Donald E. Humphries, Ph.D., Luis E. Selva, Ph.D. (VA Boston Healthcare System). MVP Informatics, Boston?Nhan Do, M.D., Shahpoor Shayan (VA Boston Healthcare System). MVP Data Operations/Analytics, Boston?Kelly Cho, Ph.D. (VA Boston Healthcare System). MVP Science: Science Operations?Christopher J. O'Donnell, M.D., M.P.H. (VA Boston Healthcare System). Genomics Core? Christopher J. O'Donnell, M.D., M.P.H., Saiju Pyarajan, Ph.D. (VA Boston Healthcare System), Philip S. Tsao, Ph.D. (VA Palo Alto Health Care System). Phenomics Core?Kelly Cho, M.P.H., Ph.D. (VA Boston Healthcare System). Data and Computational Sciences?Saiju Pyarajan, Ph.D. (VA Boston Healthcare System). Statistical Genetics?Elizabeth Hauser, Ph.D. (Durham VA Medical Center). Yan Sun, Ph.D. (Atlanta VA Medical Center). Hongyu Zhao, Ph.D. (West Haven VA Medical Center. Current MVP Local Site Investigators: Peter Wilson, M.D. (Atlanta VA Medical Center); Rachel McArdle, Ph.D. (Bay Pines VA Healthcare System); Louis Dellitalia, M.D. (Birmingham VA Medical Center); Kristin Mattocks, Ph.D., M.P.H. (Central Western Massachusetts Healthcare System); John Harley, M.D., Ph.D. (Cincinnati VA Medical Center); Clement J. Zablocki (VA Medical Center); Jeffrey Whittle, M.D., M.P.H.; Frank Jacono, M.D. (VA Northeast Ohio Healthcare System); Jean Beckham, Ph.D. (Durham VA Medical Center); Edith Nourse Rogers Memorial Veterans Hospital; Salvador Gutierrez, M.D. (Edward Hines, Jr. VA Medical Center); Gretchen Gibson, D.D.S., M.P.H. (Veterans Health Care System of the Ozarks); Kimberly Hammer, Ph.D. (Fargo VA Health Care System); Laurence Kaminsky, Ph.D. (VA Health Care Upstate New York); Gerardo Villareal, M.D. (New Mexico VA Health Care System); Scott Kinlay, M.B.B.S., Ph.D. (VA Boston Healthcare System); Junzhe Xu, M.D. (VA Western New York Healthcare System); Mark Hamner, M.D. (Ralph H. Johnson VA Medical Center); Roy Mathew, M.D. (Columbia VA Health Care System); Sujata Bhushan, M.D. (VA North Texas Health Care System); Pran Iruvanti, DO, Ph.D. (Hampton VA Medical Center); Michael Godschalk, M.D. (Richmond VA Medical Center); Zuhair Ballas, M.D. (Iowa City VA Health Care System); Douglas Ivins, M.D. (Eastern Oklahoma VA Health Care System); Stephen Mastorides, M.D. (James A. Haley Veterans? Hospital); Jonathan Moorman, M.D., Ph.D. (James H. Quillen VA Medical Center); Saib Gappy, M.D. (John D. Dingell VA Medical Center); Jon Klein, M.D., Ph.D. (Louisville VA Medical Center); Nora Ratcliffe, M.D. (Manchester VA Medical Center); Hermes Florez, M.D., Ph.D. (Miami VA Health Care System); Olaoluwa Okusaga, M.D. (Michael E. DeBakey VA Medical Center); Maureen Murdoch, M.D., M.P.H. (Minneapolis VA Health Care System); Peruvemba Sriram, M.D. (N FL/S GA Veterans Health System); Shing Shing Yeh, Ph.D., M.D. (Northport VA Medical Center); Neeraj Tandon, M.D. (Overton Brooks VA Medical Center); Darshana Jhala, M.D. (Philadelphia VA Medical Center); Samuel Aguayo, M.D. (Phoenix VA Health Care System); David Cohen, M.D. (Portland VA Medical Center); Satish Sharma, M.D. (Providence VA Medical Center); Suthat Liangpunsakul, M.D., M.P.H. (Richard Roudebush VA Medical Center); Kris Ann Oursler, M.D. (Salem VA Medical Center); Mary Whooley, M.D. (San Francisco VA Health Care System); Sunil Ahuja, M.D. (South Texas Veterans Health Care System); Joseph Constans, Ph.D. (Southeast Louisiana Veterans Health Care System); Paul Meyer, M.D., Ph.D. (Southern Arizona VA Health Care System); Jennifer Greco, M.D. (Sioux Falls VA Health Care System); Michael Rauchman, M.D. (St. Louis VA Health Care System); Richard Servatius, Ph.D. (Syracuse VA Medical Center); Melinda Gaddy, Ph.D. (VA Eastern Kansas Health Care System); Agnes Wallbom, M.D., M.S. (VA Greater Los Angeles Health Care System); Timothy Morgan, M.D. (VA Long Beach Healthcare System); Todd Stapley, D.O. (VA Maine Healthcare System); Scott Sherman, M.D., M.P.H. (VA New York Harbor Healthcare System); George Ross, M.D. (VA Pacific Islands Health Care System); Philip Tsao, Ph.D. (VA Palo Alto Health Care System); Patrick Strollo Jr., M.D. (VA Pittsburgh Health Care System); Edward Boyko, M.D. (VA Puget Sound Health Care System); Laurence Meyer, M.D., Ph.D. (VA Salt Lake City Health Care System); Samir Gupta, M.D., M.S.C.S. (VA San Diego Healthcare System); Mostaqul Huq, Pharm.D., Ph.D. (VA Sierra Nevada Health Care System); Joseph Fayad, M.D. (VA Southern Nevada Healthcare System); Adriana Hung, M.D., M.P.H. (VA Tennessee Valley Healthcare System); Jack Lichy, M.D., Ph.D. (Washington, DC VA Medical Center); Robin Hurley, M.D. (W.G., Bill Hefner VA Medical Center); Brooks Robey, M.D. (White River Junction VA Medical Center); and Robert Striker, M.D., Ph.D. (William S. Middleton Memorial Veterans Hospital). Statistical analyses were carried out on the NL Genetic Cluster Computer ( http://www.geneticcluster.org ) hosted by SURFsara and the Mount Sinai high performance computing cluster ( http://hpc.mssm.edu ), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880 ). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University , Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM]).
| Funders | Funder number |
|---|---|
| Scott Kinlay | |
| VA Western New York Healthcare System | |
| Sumitra Muralidhar | |
| Fresenius Medical Care North America | |
| H. Lundbeck A/S | |
| Samuel Aguayo | |
| Melinda Gaddy | |
| Edith Nourse Rogers Memorial Veterans Hospital | |
| Hualin S. Xi112 | |
| Satish Sharma | |
| Rachel Ramoni | |
| Takeda Pharmaceuticals U.S.A. | |
| Ferrer | |
| Peruvemba Sriram | |
| Joseph Fayad | |
| VA Eastern Kansas Health Care System | |
| Joseph Constans | |
| ACADIA Pharmaceuticals | |
| FUMA | |
| BioXcel Therapeutics | |
| James A. Haley Veterans? | |
| VA North Texas Health Care System | |
| Shire | |
| AbbVie | |
| Actelion Pharmaceuticals | |
| Oxeia Biopharmaceuticals | |
| Takeda Pharmaceutical Company | |
| Laurence Kaminsky | |
| Eli Lilly and Company | |
| Datastat, Inc. | |
| Olaoluwa Okusaga | |
| VA Long Beach Healthcare System | |
| Mount Sinai high performance computing cluster | |
| VA Northeast Ohio Healthcare System | |
| Haplotype Reference Consortium | |
| VA Southern Nevada Healthcare System | |
| Novartis | |
| Michael Godschalk | |
| Janssen Pharmaceuticals | |
| VA Tennessee Valley Healthcare System | |
| Hermes Florez | |
| Southeast Louisiana Veterans Health Care System | |
| shareholder in Johnson & Johnson | |
| Brain and Behavior Research Foundation | |
| Eastern Oklahoma VA Health Care System | |
| Saira Saeed Mirza36 | |
| Shing Shing Yeh | |
| VA Boston Healthcare System | |
| HealthLytix | |
| U.S. Department of Veterans Affairs | |
| South Texas Veterans Health Care System | |
| Farnush Farhadi Hassan Kiadeh42 | |
| Sujata Bhushan | |
| American Society of Clinical Psychopharmacology | |
| National Alliance for Research on Schizophrenia and Depression | phs001254, 29551 |
| National Alliance for Research on Schizophrenia and Depression | |
| Mariam Al Eissa40 | Scherag156, Youl-Ri Kim109, Guzman-Parra91 |
| Vanderbilt University | R01MH116269, R01MH121455 |
| Vanderbilt University | |
| National Institute of General Medical Sciences | T32GM007347 |
| National Institute of General Medical Sciences | |
| National Institutes of Health | S10OD026880, S10OD018522, R01MH116269, R01MH121455 |
| National Institutes of Health | |
| Japan Society for the Promotion of Science | 21K15712 |
| Japan Society for the Promotion of Science |
Keywords
- Genetic correlation
- Genome-wide association study
- Pleiotropy
- Polygenicity
- Suicide
- Suicide attempt
