Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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Publication Date: | 2022 |
Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/10316/100469 https://doi.org/10.1016/j.biopsych.2021.05.029 |
Summary: | 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. |
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk FactorsGenetic correlationGenome-wide association studyPleiotropyPolygenicitySuicideSuicide attemptGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk FactorsSuicide, AttemptedDepressive Disorder, MajorMental DisordersBackground: 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.2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/100469http://hdl.handle.net/10316/100469https://doi.org/10.1016/j.biopsych.2021.05.029eng00063223Mullins, NiamhKang, JooEunCampos, Adrian IColeman, Jonathan R IEdwards, Alexis CGalfalvy, HangaLevey, Daniel FLori, AdrianaShabalin, AndreyStarnawska, AnnaSu, Mei-HsinWatson, Hunna JAdams, MarkAwasthi, SwapnilGandal, MichaelHafferty, Jonathan DHishimoto, AkitoyoKim, MinsooOkazaki, SatoshiOtsuka, IkuoRipke, StephanWare, Erin BBergen, Andrew WBerrettini, Wade HBohus, MartinBrandt, HarryChang, XiaoChen, Wei JChen, Hsi-ChungCrawford, StevenCrow, ScottDiBlasi, EmilyDuriez, PhilibertFernández-Aranda, FernandoFichter, Manfred MGallinger, StevenGlatt, Stephen JGorwood, PhilipGuo, YiranHakonarson, HakonHalmi, Katherine AHwu, Hai-GwoJain, SoniaJamain, StéphaneJiménez-Murcia, SusanaJohnson, CraigKaplan, Allan SKaye, Walter HKeel, Pamela KKennedy, James L.Klump, Kelly LLi, DongLiao, Shih-ChengLieb, KlausLilenfeld, LisaLiu, Chih-MinMagistretti, Pierre JMarshall, Christian RMitchell, James EMonson, EricMyers, Richard MPinto, DalilaPowers, AbigailRamoz, NicolasRoepke, StefanRozanov, VsevolodScherer, Stephen WSchmahl, ChristianSokolowski, MarcusStrober, MichaelThornton, Laura MTreasure, JanetTsuang, Ming TWitt, Stephanie HWoodside, D BlakeYilmaz, ZeynepZillich, LeaAdolfsson, RolfAgartz, IngridAir, Tracy MAlda, MartinAlfredsson, LarsAndreassen, Ole AAnjorin, AdebayoAppadurai, VivekSoler Artigas, MaríaVan der Auwera, SandraAzevedo, M. HelenaBass, NicholasBau, Claiton H DBaune, Bernhard TBellivier, FrankBerger, KlausBiernacka, Joanna MBigdeli, Tim BBinder, Elisabeth B.Boehnke, MichaelBoks, Marco PBosch, RosaBraff, David LBryant, RichardBudde, MonikaByrne, Enda MCahn, WiepkeCasas, MiguelCastelao, EnriqueCervilla, Jorge AChaumette, BorisCichon, SvenCorvin, AidenCraddock, NicholasCraig, DavidDegenhardt, FranziskaDjurovic, SrdjanEdenberg, Howard JFanous, Ayman HFoo, Jerome CForstner, Andreas JFrye, MarkFullerton, Janice MGatt, Justine MGejman, Pablo VGiegling, InaGrabe, Hans JGreen, Melissa JGrevet, Eugenio HGrigoroiu-Serbanescu, MariaGutierrez, BlancaGuzman-Parra, JoseHamilton, Steven PHamshere, Marian LHartmann, AnnetteHauser, JoannaHeilmann-Heimbach, StefanieHoffmann, PerIsing, MarcusJones, IanJones, Lisa AJonsson, LinaKahn, René SKelsoe, John RKendler, Kenneth SKloiber, StefanKoenen, Karestan CKogevinas, ManolisKonte, BettinaKrebs, Marie-OdileLandén, MikaelLawrence, JacobLeboyer, MarionLee, Phil HLevinson, Douglas FLiao, CalwingLissowska, JolantaLucae, SusanneMayoral, FerminMcElroy, Susan LMcGrath, PatrickMcGuffin, PeterMcQuillin, AndrewMedland, Sarah EMehta, DivyaMelle, IngridMilaneschi, YuriMitchell, Philip BMolina, EstherMorken, GunnarMortensen, Preben BoMüller-Myhsok, BertramNievergelt, CarolineNimgaonkar, VishwajitNöthen, Markus MO'Donovan, Michael C.Ophoff, Roel AOwen, Michael J.Pato, CarlosPato, Michele TPenninx, Brenda W J HPimm, JonathanPistis, GiorgioPotash, James BPower, Robert APreisig, MartinQuested, DigbyRamos-Quiroga, Josep AntoniReif, AndreasRibasés, MartaRicharte, VanesaRietschel, MarcellaRivera, MargaritaRoberts, AndreaRoberts, GloriaRouleau, Guy ARovaris, Diego LRujescu, DanSánchez-Mora, CristinaSanders, Alan RSchofield, Peter RSchulze, Thomas GScott, Laura JSerretti, AlessandroShi, JianxinShyn, Stanley ISirignano, LeaSklar, PamelaSmeland, Olav BSmoller, Jordan WSonuga-Barke, Edmund J SSpalletta, GianfrancoStrauss, John SŚwiątkowska, BeataTrzaskowski, MaciejTurecki, GustavoVilar-Ribó, LauraVincent, John B.Völzke, HenryWalters, James T RShannon Weickert, CynthiaWeickert, Thomas WWeissman, Myrna MWilliams, Leanne MWray, Naomi RZai, Clement CAshley-Koch, Allison EBeckham, Jean CHauser, Elizabeth RHauser, Michael AKimbrel, Nathan ALindquist, Jennifer HMcMahon, BenjaminOslin, David WQin, XuejunAgerbo, EsbenBørglum, Anders DBreen, GeromeErlangsen, AnnetteEsko, TõnuGelernter, JoelHougaard, David MKessler, Ronald CKranzler, Henry RLi, Qingqin SMartin, Nicholas GMcIntosh, Andrew MMors, OleNordentoft, MereteOlsen, Catherine MPorteous, DavidUrsano, Robert JWasserman, DanutaWerge, ThomasWhiteman, David CBulik, Cynthia MCoon, HilaryDemontis, DitteDocherty, Anna RKuo, Po-HsiuLewis, Cathryn MMann, J JohnRentería, Miguel ESmith, Daniel JStahl, Eli AStein, Murray BStreit, FabianWillour, VirginiaRuderfer, Douglas Minfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-06-21T20:30:58Zoai:estudogeral.uc.pt:10316/100469Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:17:51.029065Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
title |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
spellingShingle |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors Mullins, Niamh Genetic correlation Genome-wide association study Pleiotropy Polygenicity Suicide Suicide attempt Genome-Wide Association Study Humans Polymorphism, Single Nucleotide Risk Factors Suicide, Attempted Depressive Disorder, Major Mental Disorders |
title_short |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
title_full |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
title_fullStr |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
title_full_unstemmed |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
title_sort |
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors |
author |
Mullins, Niamh |
author_facet |
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 |
author_role |
author |
author2 |
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 |
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author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
Genetic correlation Genome-wide association study Pleiotropy Polygenicity Suicide Suicide attempt Genome-Wide Association Study Humans Polymorphism, Single Nucleotide Risk Factors Suicide, Attempted Depressive Disorder, Major Mental Disorders |
topic |
Genetic correlation Genome-wide association study Pleiotropy Polygenicity Suicide Suicide attempt Genome-Wide Association Study Humans Polymorphism, Single Nucleotide Risk Factors Suicide, Attempted Depressive Disorder, Major Mental Disorders |
description |
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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/100469 http://hdl.handle.net/10316/100469 https://doi.org/10.1016/j.biopsych.2021.05.029 |
url |
http://hdl.handle.net/10316/100469 https://doi.org/10.1016/j.biopsych.2021.05.029 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
00063223 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134074241024000 |