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Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

By Niamh Mullins, Jooeun Kang, Adrian I Campos, Jonathan RI Coleman, Alexis C Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark N Adams, Swapnil Awasthi, Michael J Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew Wells 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, Stephane JAMAIN, Susana Jiménez-Murcia, W. Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K Keel, James Kennedy, Kelly L Klump, Maria La Via, Robert D. Levitan, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre Julius Magistretti, Christian R Marshall, James E Mitchell, Eric T Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Alessandro Rotondo, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T Tsuang, Robert J Ursano, Stephanie Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M Air, Martin Alda, Lars Alfredsson, Ole Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, M. Helena Azevedo, Nicholas Bass, Claiton HD Bau, Bernhard T Baune, Frank BELLIVIER, Klaus Berger, Joanna M Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco 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-Jorgen Grabe, Melissa J Green, Eugenio H Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P Hamilton, Marian L Hamshere, Annette M Hartmann, Joanna Twarowska-Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A Jones, Lina Jonsson, René S. Kahn, John R Kelsoe, Kenneth 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 Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Mueller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M Nothen, Michael C O'Donovan, Roel A Ophoff, Michael J Owen, Carlos Pato, Michele Pato, Brenda WJH 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 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 Swiatkowska, Maciej Trzaskowski, Gustavo Turecki, Sandra Van der Auwera, Laura Vilar-Ribó, John B Vincent, Henry Völzke, James TR Walters, Cynthia Shannon Weickert, Thomas W Weickert, Myrna M Weissman, Leanne M Williams, Naomi R. Wray, Clement Zai, Esben Agerbo, Anders D. Børglum, Inti Pedroso, Annette Erlangsen, Tonu Esko, Joel Gelernter, David M Hougaard, Ronald C Kessler, Henry R. Kranzler, Qingqin S Li, Nicholas G Martin, Andrew McIntosh, Sarah E. Medland, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia Bulik, Hilary Coon, Ditte Demontis, Anna Docherty, Po-Hsiu Kuo, Cathryn Lewis, J John Mann, Miguel Renteria, Daniel J Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M Ruderfer

Posted 04 Dec 2020
medRxiv DOI: 10.1101/2020.12.01.20241281

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.

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