Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/100469
Title: Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
Authors: Mullins, Niamh
Kang, JooEun
Campos, Adrian I
Coleman, Jonathan R I
Edwards, Alexis C
Galfalvy, Hanga
Levey, Daniel F
Lori, Adriana
Shabalin, Andrey
Starnawska, Anna
Su, Mei-Hsin
Watson, Hunna J
Adams, Mark
Awasthi, Swapnil
Gandal, Michael
Hafferty, Jonathan D
Hishimoto, Akitoyo
Kim, Minsoo
Okazaki, Satoshi
Otsuka, Ikuo
Ripke, Stephan
Ware, Erin B
Bergen, Andrew W
Berrettini, Wade H
Bohus, Martin
Brandt, Harry
Chang, Xiao
Chen, Wei J
Chen, Hsi-Chung
Crawford, Steven
Crow, Scott
DiBlasi, Emily
Duriez, Philibert
Fernández-Aranda, Fernando
Fichter, Manfred M
Gallinger, Steven
Glatt, Stephen J
Gorwood, Philip
Guo, Yiran
Hakonarson, Hakon
Halmi, Katherine A
Hwu, Hai-Gwo
Jain, Sonia
Jamain, Stéphane
Jiménez-Murcia, Susana
Johnson, Craig
Kaplan, Allan S
Kaye, Walter H
Keel, Pamela K
Kennedy, James L. 
Klump, Kelly L
Li, Dong
Liao, Shih-Cheng
Lieb, Klaus
Lilenfeld, Lisa
Liu, Chih-Min
Magistretti, Pierre J
Marshall, Christian R
Mitchell, James E
Monson, Eric 
Myers, Richard M
Pinto, Dalila
Powers, Abigail
Ramoz, Nicolas
Roepke, Stefan
Rozanov, Vsevolod
Scherer, Stephen W
Schmahl, Christian
Sokolowski, Marcus
Strober, Michael
Thornton, Laura M
Treasure, Janet
Tsuang, Ming T
Witt, Stephanie H
Woodside, D Blake
Yilmaz, Zeynep
Zillich, Lea
Adolfsson, Rolf
Agartz, Ingrid
Air, Tracy M
Alda, Martin
Alfredsson, Lars
Andreassen, Ole A
Anjorin, Adebayo
Appadurai, Vivek
Soler Artigas, María
Van der Auwera, Sandra
Azevedo, M. Helena 
Bass, Nicholas
Bau, Claiton H D
Baune, Bernhard T
Bellivier, Frank
Berger, Klaus
Biernacka, Joanna M
Bigdeli, Tim B
Binder, Elisabeth B. 
Boehnke, Michael
Boks, Marco P
Bosch, Rosa
Braff, David L
Bryant, Richard
Budde, Monika
Byrne, Enda M
Cahn, Wiepke
Casas, Miguel
Castelao, Enrique
Cervilla, Jorge A
Chaumette, Boris
Cichon, Sven
Corvin, Aiden
Craddock, Nicholas
Craig, David
Degenhardt, Franziska
Djurovic, Srdjan
Edenberg, Howard J
Fanous, Ayman H
Foo, Jerome C
Forstner, Andreas J
Frye, Mark
Fullerton, Janice M
Gatt, Justine M
Gejman, Pablo V
Giegling, Ina
Grabe, Hans J
Green, Melissa J
Grevet, Eugenio H
Grigoroiu-Serbanescu, Maria
Gutierrez, Blanca
Guzman-Parra, Jose
Hamilton, Steven P
Hamshere, Marian L
Hartmann, Annette
Hauser, Joanna
Heilmann-Heimbach, Stefanie
Hoffmann, Per
Ising, Marcus
Jones, Ian
Jones, Lisa A
Jonsson, Lina
Kahn, René S
Kelsoe, John R
Kendler, Kenneth S
Kloiber, Stefan
Koenen, Karestan C
Kogevinas, Manolis
Konte, Bettina
Krebs, Marie-Odile
Landén, Mikael
Lawrence, Jacob
Leboyer, Marion
Lee, Phil H
Levinson, Douglas F
Liao, Calwing
Lissowska, Jolanta
Lucae, Susanne
Mayoral, Fermin
McElroy, Susan L
McGrath, Patrick
McGuffin, Peter
McQuillin, Andrew
Medland, Sarah E
Mehta, Divya
Melle, Ingrid
Milaneschi, Yuri
Mitchell, Philip B
Molina, Esther
Morken, Gunnar
Mortensen, Preben Bo
Müller-Myhsok, Bertram
Nievergelt, Caroline
Nimgaonkar, Vishwajit
Nöthen, Markus M
O'Donovan, Michael C. 
Ophoff, Roel A
Owen, Michael J. 
Pato, Carlos
Pato, Michele T
Penninx, Brenda W J H
Pimm, Jonathan
Pistis, Giorgio
Potash, James B
Power, Robert A
Preisig, Martin
Quested, Digby
Ramos-Quiroga, Josep Antoni
Reif, Andreas
Ribasés, Marta
Richarte, Vanesa
Rietschel, Marcella
Rivera, Margarita
Roberts, Andrea
Roberts, Gloria
Rouleau, Guy A
Rovaris, Diego L
Rujescu, Dan
Sánchez-Mora, Cristina
Sanders, Alan R
Schofield, Peter R
Schulze, Thomas G
Scott, Laura J
Serretti, Alessandro
Shi, Jianxin
Shyn, Stanley I
Sirignano, Lea
Sklar, Pamela
Smeland, Olav B
Smoller, Jordan W
Sonuga-Barke, Edmund J S
Spalletta, Gianfranco
Strauss, John S
Świątkowska, Beata
Trzaskowski, Maciej
Turecki, Gustavo
Vilar-Ribó, Laura
Vincent, John B. 
Völzke, Henry
Walters, James T R
Shannon Weickert, Cynthia
Weickert, Thomas W
Weissman, Myrna M
Williams, Leanne M
Wray, Naomi R
Zai, Clement C
Ashley-Koch, Allison E
Beckham, Jean C
Hauser, Elizabeth R
Hauser, Michael A
Kimbrel, Nathan A
Lindquist, Jennifer H
McMahon, Benjamin
Oslin, David W
Qin, Xuejun
Agerbo, Esben
Børglum, Anders D
Breen, Gerome
Erlangsen, Annette
Esko, Tõnu
Gelernter, Joel
Hougaard, David M
Kessler, Ronald C
Kranzler, Henry R
Li, Qingqin S
Martin, Nicholas G
McIntosh, Andrew M
Mors, Ole
Nordentoft, Merete
Olsen, Catherine M
Porteous, David
Ursano, Robert J
Wasserman, Danuta
Werge, Thomas
Whiteman, David C
Bulik, Cynthia M
Coon, Hilary
Demontis, Ditte
Docherty, Anna R
Kuo, Po-Hsiu
Lewis, Cathryn M
Mann, J John
Rentería, Miguel E
Smith, Daniel J
Stahl, Eli A
Stein, Murray B
Streit, Fabian
Willour, Virginia
Ruderfer, Douglas M
Keywords: Genetic correlation; Genome-wide association study; Pleiotropy; Polygenicity; Suicide; Suicide attempt
Issue Date: 2022
Project: National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880) 
National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]) 
National Institutes of Health (Grant No. T32GM007347 [to JK]) 
Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM]) 
Serial title, monograph or event: Biological Psychiatry
Volume: 91
Issue: 3
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.
URI: http://hdl.handle.net/10316/100469
ISSN: 00063223
DOI: 10.1016/j.biopsych.2021.05.029
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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