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