Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1016/j.biopsych.2021.05.029

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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
Early online date	8 Sept 2021
DOIs	https://doi.org/10.1016/j.biopsych.2021.05.029
Publication status	Published - 1 Feb 2022

Keywords / Materials (for Non-textual outputs)

Genetic correlation
Genome-wide association study
Pleiotropy
Polygenicity
Suicide
Suicide attempt

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10.1016/j.biopsych.2021.05.029Licence: CC BY-NC-ND

PIIS0006322321015705Final published version, 0.99 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

https://linkinghub.elsevier.com/retrieve/pii/S0006322321015705

Cite this

@article{a9489460978f42b3873435359d65b42c,

title = "Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors",

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.",

keywords = "Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt",

author = "{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Niamh Mullins and Jooeun Kang and Campos, {Adrian I.} and Coleman, {Jonathan R.i.} and Edwards, {Alexis C.} and Hanga Galfalvy and Levey, {Daniel F.} and Adriana Lori and Andrey Shabalin and Anna Starnawska and Mei-hsin Su and Watson, {Hunna J.} and Mark Adams and Swapnil Awasthi and Michael Gandal and Hafferty, {Jonathan D.} and Akitoyo Hishimoto and Minsoo Kim and Satoshi Okazaki and Ikuo Otsuka and Stephan Ripke and Ware, {Erin B.} and Bergen, {Andrew W.} and Berrettini, {Wade H.} and Martin Bohus and Harry Brandt and Xiao Chang and Chen, {Wei J.} and Hsi-chung Chen and Steven Crawford and Scott Crow and Emily Diblasi and Philibert Duriez and Fernando Fern{\'a}ndez-aranda and Fichter, {Manfred M.} and Steven Gallinger and Glatt, {Stephen J.} and Philip Gorwood and Yiran Guo and Hakon Hakonarson and Halmi, {Katherine A.} and Hai-gwo Hwu and Sonia Jain and St{\'e}phane Jamain and Susana Jim{\'e}nez-murcia and Craig Johnson and Kaplan, {Allan S.} and Kaye, {Walter H.} and Keel, {Pamela K.} and Kennedy, {James L.} and Klump, {Kelly L.} and Dong Li and Shih-cheng Liao and Klaus Lieb and Lisa Lilenfeld and Chih-min Liu and Magistretti, {Pierre J.} and Marshall, {Christian R.} and James Mitchell and Monson, {Eric T.} and Myers, {Richard M.} and Dalila Pinto and Abigail Powers and Nicolas Ramoz and Stefan Roepke and Vsevolod Rozanov and Scherer, {Stephen W.} and Christian Schmahl and Marcus Sokolowski and Michael Strober and Thornton, {Laura M.} and Janet Treasure and Tsuang, {Ming T.} and Witt, {Stephanie H.} and Woodside, {D. Blake} and Zeynep Yilmaz and Lea Zillich and Rolf Adolfsson and Ingrid Agartz and Air, {Tracy M.} and Martin Alda and Lars Alfredsson and Andreassen, {Ole A.} and Adebayo Anjorin and Vivek Appadurai and {Soler Artigas}, Mar{\'i}a and {Der Auwera}, {Sandra Van} and Azevedo, {M. Helena} and Nicholas Bass and Bau, {Claiton H.d.} and Baune, {Bernhard T.} and Frank Bellivier and Klaus Berger and Biernacka, {Joanna M.} and Bigdeli, {Tim B.} and Binder, {Elisabeth B.} and Michael Boehnke and Boks, {Marco P.} and Rosa Bosch and Braff, {David L.} and Richard Bryant and Monika Budde and Byrne, {Enda M.} and Wiepke Cahn and Miguel Casas and Enrique Castelao and Cervilla, {Jorge A.} and Boris Chaumette and Sven Cichon and Aiden Corvin and Nicholas Craddock and David Craig and Franziska Degenhardt and Srdjan Djurovic and Edenberg, {Howard J.} and Fanous, {Ayman H.} and Foo, {Jerome C.} and Forstner, {Andreas J.} and Mark Frye and Fullerton, {Janice M.} and Gatt, {Justine M.} and Gejman, {Pablo V.} and Ina Giegling and Grabe, {Hans J.} and Green, {Melissa J.} and Grevet, {Eugenio H.} and Maria Grigoroiu-serbanescu and Blanca Gutierrez and Jose Guzman-parra and Hamilton, {Steven P.} and Hamshere, {Marian L.} and Annette Hartmann and Joanna Hauser and Stefanie Heilmann-heimbach and Per Hoffmann and Marcus Ising and Ian Jones and Jones, {Lisa A.} and Lina Jonsson and Kahn, {Ren{\'e} S.} and Kelsoe, {John R.} and Kendler, {Kenneth S.} and Stefan Kloiber and Koenen, {Karestan C.} and Manolis Kogevinas and Bettina Konte and Marie-odile Krebs and Mikael Land{\'e}n and Jacob Lawrence and Marion Leboyer and Lee, {Phil H.} and Levinson, {Douglas F.} and Calwing Liao and Jolanta Lissowska and Susanne Lucae and Fermin Mayoral and Mcelroy, {Susan L.} and Patrick Mcgrath and Peter Mcguffin and Andrew Mcquillin and Medland, {Sarah E.} and Divya Mehta and Ingrid Melle and Yuri Milaneschi and Mitchell, {Philip B.} and Esther Molina and Gunnar Morken and Mortensen, {Preben Bo} and Bertram M{\"u}ller-myhsok and Nievergelt, {Caroline M.} and Vishwajit Nimgaonkar and N{\"o}then, {Markus M.} and O{\textquoteright}donovan, {Michael C.} and Ophoff, {Roel A.} and Owen, {Michael J.} and Carlos Pato and Pato, {Michele T.} and Penninx, {Brenda W.j.h.} and Jonathan Pimm and Giorgio Pistis and Potash, {James B.} and Power, {Robert A.} and Martin Preisig and Digby Quested and Ramos-quiroga, {Josep Antoni} and Andreas Reif and Marta Ribas{\'e}s and Vanesa Richarte and Marcella Rietschel and Margarita Rivera and Andrea Roberts and Gloria Roberts and Rouleau, {Guy A.} and Rovaris, {Diego L.} and Dan Rujescu and Cristina S{\'a}nchez-mora and Sanders, {Alan R.} and Schofield, {Peter R.} and Schulze, {Thomas G.} and Scott, {Laura J.} and Alessandro Serretti and Jianxin Shi and Shyn, {Stanley I.} and Lea Sirignano and Pamela Sklar and Smeland, {Olav B.} and Smoller, {Jordan W.} and Sonuga-barke, {Edmund J.s.} and Gianfranco Spalletta and Strauss, {John S.} and Beata {\'S}wi{\c a}tkowska and Maciej Trzaskowski and Gustavo Turecki and Laura Vilar-rib{\'o} and Vincent, {John B.} and Henry V{\"o}lzke and Walters, {James T.r.} and {Shannon Weickert}, Cynthia and Weickert, {Thomas W.} and Weissman, {Myrna M.} and Williams, {Leanne M.} and Wray, {Naomi R.} and Zai, {Clement C.} and Ashley-koch, {Allison E.} and Jean Beckham and Hauser, {Elizabeth R.} and Hauser, {Michael A.} and Kimbrel, {Nathan A.} and Lindquist, {Jennifer H.} and Benjamin Mcmahon and Oslin, {David W.} and Xuejun Qin and Esben Agerbo and B{\o}rglum, {Anders D.} and Gerome Breen and Annette Erlangsen and T{\~o}nu Esko and Joel Gelernter and Hougaard, {David M.} and Kessler, {Ronald C.} and Kranzler, {Henry R.} and Li, {Qingqin S.} and Martin, {Nicholas G.} and Mcintosh, {Andrew M.} and Ole Mors and Merete Nordentoft and Olsen, {Catherine M.} and Porteous, {David J.} and Ursano, {Robert J.} and Danuta Wasserman and Thomas Werge and Whiteman, {David C.} and Bulik, {Cynthia M.} and Hilary Coon and Ditte Demontis and Docherty, {Anna R.} and Po-hsiu Kuo and Lewis, {Cathryn M.} and Mann, {J. 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Raymond} and Enrico Domenici and Katharina Domschke and T{\~o}nu Esko and Grabe, {Hans J.} and Hamilton, {Steven P.} and Jakob Grove and Hall, {Lynsey S.} and Hansen, {Christine S{\o}holm} and Hansen, {Thomas F.} and Stefan Herms and Hickie, {Ian B.} and Per Hoffmann and Georg Homuth and Carsten Horn and Jouke-jan Hottenga and Hougaard, {David M.} and Howard, {David M.} and Marcus Ising and Rick Jansen and Ian Jones and Jones, {Lisa A.} and Eric Jorgenson and Knowles, {James A.} and Kohane, {Isaac S.} and Julia Kraft and Kretzschmar, {Warren W.} and Zolt{\'a}n Kutalik and Yihan Li and Lind, {Penelope A.} and Macintyre, {Donald J.} and Mackinnon, {Dean F.} and Maier, {Robert M.} and Wolfgang Maier and Jonathan Marchini and Hamdi Mbarek and Patrick Mcgrath and Peter Mcguffin and Medland, {Sarah E.} and Divya Mehta and Middeldorp, {Christel M.} and Evelin Mihailov and Yuri Milaneschi and Lili Milani and Mondimore, {Francis M.} and Montgomery, {Grant W.} and Sara Mostafavi and Niamh Mullins and Matthias Nauck and Bernard Ng and Nivard, {Michel G.} and Nyholt, {Dale R.} and O{\textquoteright}reilly, {Paul F.} and Hogni Oskarsson and Caroline Hayward and Heath, {Andrew C.} and Kendler, {Kenneth S.} and Stefan Kloiber and Glyn Lewis and Li, {Qingqin S.} and Susanne Lucae and Madden, {Pamela A.f.} and Magnusson, {Patrik K.} and Martin, {Nicholas G.} and Mcintosh, {Andrew M.} and Andres Metspalu and Ole Mors and Mortensen, {Preben Bo} and Bertram M{\"u}ller-myhsok and Merete Nordentoft and N{\"o}then, {Markus M.} and O{\textquoteright}donovan, {Michael C.} and Paciga, {Sara A.} and Pedersen, {Nancy L.} and Owen, {Michael J.} and Painter, {Jodie N.} and Pedersen, {Carsten B{\o}cker} and Pedersen, {Marianne Gi{\o}rtz} and Peterson, {Roseann E.} and Peyrot, {Wouter J.} and Giorgio Pistis and Danielle Posthuma and Quiroz, {Jorge A.} and Per Qvist and Rice, {John P.} and Riley, {Brien P.} and Margarita Rivera and Mirza, {Saira Saeed} and Robert Schoevers and Schulte, {Eva C.} and Ling Shen and Jianxin Shi and Shyn, {Stanley I.} and Engilbert Sigurdsson and Sinnamon, {Grant C.b.} and Smit, {Johannes H.} and Smith, {Daniel J.} and Hreinn Stefansson and Stacy Steinberg and Fabian Streit and Jana Strohmaier and Tansey, {Katherine E.} and Henning Teismann and Alexander Teumer and Wesley Thompson and Thomson, {Pippa A.} and Thorgeirsson, {Thorgeir E.} and Matthew Traylor and Jens Treutlein and Vassily Trubetskoy and Uitterlinden, {Andr{\'e} G.} and Daniel Umbricht and {Der Auwera}, {Sandra Van} and {Van Hemert}, {Albert M.} and Alexander Viktorin and Visscher, {Peter M.} and Yunpeng Wang and Webb, {Bradley T.} and Penninx, {Brenda W.j.h.} and Perlis, {Roy H.} and Porteous, {David J.} and Potash, {James B.} and Martin Preisig and Marcella Rietschel and Catherine Schaefer and Schulze, {Thomas G.} and Smoller, {Jordan W.} and Kari Stefansson and Henning Tiemeier and Rudolf Uher and Henry V{\"o}lzke and Weissman, {Myrna M.} and Thomas Werge and Lewis, {Cathryn M.} and Levinson, {Douglas F.} and Gerome Breen and B{\o}rglum, {Anders D.} and Sullivan, {Patrick F.} and Niamh Mullins and Forstner, {Andreas J.} and O{\textquoteright}connell, {Kevin S.} and Brandon Coombes and Coleman, {Jonathan R.i.} and Zhen Qiao and Als, {Thomas D.} and Bigdeli, {Tim B.} and Sigrid B{\o}rte and Julien Bryois and Charney, {Alexander W.} and Drange, {Ole Kristian} and Gandal, {Michael J.} and Hagenaars, {Saskia P.} and Masashi Ikeda and Nolan Kamitaki and Minsoo Kim and Kristi Krebs and Georgia Panagiotaropoulou and Schilder, {Brian M.} and Sloofman, {Laura G.} and Stacy Steinberg and Vassily Trubetskoy and Winsvold, {Bendik S.} and Hong-hee Won and Liliya Abramova and Kristina Adorjan and Esben Agerbo and {Al Eissa}, Mariam and Diego Albani and Ney Alliey-rodriguez and Adebayo Anjorin and Verneri Antilla and Anastasia Antoniou and Swapnil Awasthi and Baek, {Ji Hyun} and Marie B{\ae}kvad-hansen and Nicholas Bass and Michael Bauer and Beins, {Eva C.} and Bergen, {Sarah E.} and Armin Birner and Pedersen, {Carsten B{\o}cker} and Erlend B{\o}en and Boks, {Marco P.} and Rosa Bosch and Murielle Brum and Brumpton, {Ben M.} and Nathalie Brunkhorst-kanaan and Monika Budde and Jonas Bybjerg-grauholm and William Byerley and Murray Cairns and Miquel Casas and Pablo Cervantes and Toni-kim Clarke and Cristiana Cruceanu and Alfredo Cuellar-barboza and Julie Cunningham and David Curtis and Czerski, {Piotr M.} and Dale, {Anders M.} and Nina Dalkner and David, {Friederike S.} and Franziska Degenhardt and Srdjan Djurovic and Dobbyn, {Amanda L.} and Athanassios Douzenis and Torbj{\o}rn Elvs{\aa}shagen and Valentina Escott-price and Ferrier, {I. Nicol} and Alessia Fiorentino and Foroud, {Tatiana M.} and Liz Forty and Josef Frank and Oleksandr Frei and Freimer, {Nelson B.} and Louise Fris{\'e}n and Katrin Gade and Julie Garnham and Joel Gelernter and Pedersen, {Marianne Gi{\o}rtz} and Gizer, {Ian R.} and Scott Gordon and Katherine Gordon-smith and Greenwood, {Tiffany A.} and Jakob Grove and Jos{\'e} Guzman-parra and Kyooseob Ha and Magnus Haraldsson and Martin Hautzinger and Urs Heilbronner and Dennis Hellgren and Stefan Herms and Per Hoffmann and Holmans, {Peter A.} and Huckins, {Laura M.} and St{\'e}phane Jamain and Johnson, {Jessica S.} and Kalman, {Janos L.} and Yoichiro Kamatani and Kennedy, {James L.} and Sarah Kittel-schneider and Knowles, {James A.} and Manolis Kogevinas and Maria Koromina and Kranz, {Thorsten M.} and Kranzler, {Henry R.} and Michiaki Kubo and Ralph Kupka and Kushner, {Steven A.} and Catharina Lavebratt and Jacob Lawrence and Markus Leber and Heon-jeong Lee and Lee, {Phil H.} and Levy, {Shawn E.} and Catrin Lewis and Calwing Liao and Susanne Lucae and Martin Lundberg and Macintyre, {Donald J.} and Magnusson, {Sigurdur H.} and Wolfgang Maier and Adam Maihofer and Dolores Malaspina and Eirini Maratou and Lina Martinsson and Manuel Mattheisen and Mcgregor, {Nathaniel W.} and Peter Mcguffin and Mckay, {James D.} and Helena Medeiros and Medland, {Sarah E.} and Vincent Millischer and Montgomery, {Grant W.} and Moran, {Jennifer L.} and Morris, {Derek W.} and M{\"u}hleisen, {Thomas W.} and Niamh O{\textquoteright}brien and Claire O{\textquoteright}donovan and {Olde Loohuis}, {Loes M.} and Lilijana Oruc and Sergi Papiol and Pardi{\~n}as, {Antonio F.} and Amy Perry and Andrea Pfennig and Evgenia Porichi and Potash, {James B.} and Digby Quested and Towfique Raj and Rapaport, {Mark H.} and Depaulo, {J. 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and Scott, {Laura J.} and Scott, {Rodney J.} and Alessandro Serretti and Weickert, {Cynthia Shannon} and Smoller, {Jordan W.} and Hreinn Stefansson and Kari Stefansson and Eystein Stordal and Fabian Streit and Sullivan, {Patrick F.} and Gustavo Turecki and Vaaler, {Arne E.} and Eduard Vieta and Vincent, {John B.} and Waldman, {Irwin D.} and Weickert, {Thomas W.} and Thomas Werge and Wray, {Naomi R.} and John-anker Zwart and Biernacka, {Joanna M.} and Nurnberger, {John I.} and Sven Cichon and Edenberg, {Howard J.} and Stahl, {Eli A.} and Andrew Mcquillin and {Di Florio}, Arianna and Ophoff, {Roel A.} and Andreassen, {Ole A.} and Adan, {Roger A.h.} and Lars Alfredsson and Tetsuya Ando and Andreassen, {Ole A.} and Harald Aschauer and Baker, {Jessica H.} and Vladimir Bencko and Bergen, {Andrew W.} and Berrettini, {Wade H.} and Andreas Birgeg{\aa}rd and Boden, {Joseph M.} and Ilka Boehm and Claudette Boni and Perica, {Vesna Boraska} and Harry Brandt and Gerome Breen and Julien Bryois and Katharina Buehren and Bulik, {Cynthia M.} and Roland Burghardt and Laura Carlberg and Matteo Cassina and Sven Cichon and Maurizio Clementi and Coleman, {Jonathan R.i.} and Cone, {Roger D.} and Philippe Courtet and Steven Crawford and Scott Crow and Crowley, {James J.} and Danner, {Unna N.} and Davis, {Oliver S.p.} and {De Zwaan}, Martina and George Dedoussis and Daniela Degortes and Desocio, {Janiece E.} and Dick, {Danielle M.} and Dimitris Dikeos and Christian Dina and Monika Dmitrzak-weglarz and Martinez, {Elisa Docampo} and Duncan, {Laramie E.} and Karin Egberts and Marshall, {Christian R.} and Martin, {Nicholas G.} and Manuel Mattheisen and Morten Mattingsdal and Sara Mcdevitt and Peter Mcguffin and Medland, {Sarah E.} and Andres Metspalu and Ingrid Meulenbelt and Nadia Micali and James Mitchell and Karen Mitchell and Palmiero Monteleone and Monteleone, {Alessio Maria} and Montgomery, {Grant W.} and Mortensen, {Preben Bo} and Munn-chernoff, {Melissa A.} and Benedetta Nacmias and Marie Navratilova and Ioanna Ntalla and Olsen, {Catherine M.} and Ophoff, {Roel A.} and O{\textquoteright}toole, {Julie K.} and Leonid Padyukov and Aarno Palotie and Jacques Pantel and Hana Papezova and Richard Parker and Pearson, {John F.} and Pedersen, {Nancy L.} and Stefan Ehrlich and Ge{\`o}rgia Escaram{\'i}s and T{\~o}nu Esko and Thomas Espeseth and Xavier Estivill and Anne Farmer and Angela Favaro and Fernando Fern{\'a}ndez-aranda and Fichter, {Manfred M.} and Krista Fischer and Floyd, {James A.b.} and Manuel F{\"o}cker and Lenka Foretova and Forstner, {Andreas J.} and Monica Forzan and Franklin, {Christopher S.} and Steven Gallinger and Giovanni Gambaro and Gaspar, {H{\'e}l{\'e}na A.} and Ina Giegling and Johanna Giuranna and Paola Giusti-rodr{\'i}quez and Fragiskos Gonidakis and Scott Gordon and Philip Gorwood and Mayora, {Monica Gratacos} and Jakob Grove and S{\'e}bastien Guillaume and Yiran Guo and Hakon Hakonarson and Halmi, {Katherine A.} and Hanscombe, {Ken B.} and Konstantinos Hatzikotoulas and Joanna Hauser and Johannes Hebebrand and Helder, {Sietske G.} and Henders, {Anjali K.} and Stefan Herms and Beate Herpertz-dahlmann and Wolfgang Herzog and Anke Hinney and Horwood, {L. John} and Christopher H{\"u}bel and Petersen, {Liselotte V.} and Dalila Pinto and Purves, {Kirstin L.} and Anu Raevuori and Nicolas Ramoz and Ted Reichborn-kjennerud and Valdo Ricca and Samuli Ripatti and Stephan Ripke and Franziska Ritschel and Marion Roberts and Dan Rujescu and Filip Rybakowski and Paolo Santonastaso and Andr{\'e} Scherag and Scherer, {Stephen W.} and Ulrike Schmidt and Schork, {Nicholas J.} and Alexandra Schosser and Jochen Seitz and Lenka Slachtova and Slagboom, {P. Eline} and {Slof-op {\textquoteleft}t Landt}, {Margarita C.t.} and Agnieszka Slopien and Nicole Soranzo and Sandro Sorbi and Lorraine Southam and Steen, {Vidar W.} and Michael Strober and Huckins, {Laura M.} and Hudson, {James I.} and Hartmut Imgart and Hidetoshi Inoko and Vladimir Janout and Susana Jim{\'e}nez-murcia and Craig Johnson and Jennifer Jordan and Antonio Juli{\`a} and Gursharan Kalsi and Deborah Kaminsk{\'a} and Kaplan, {Allan S.} and Jaakko Kaprio and Leila Karhunen and Andreas Karwautz and Kas, {Martien J.h.} and Kaye, {Walter H.} and Kennedy, {James L.} and Kennedy, {Martin A.} and Anna Keski-rahkonen and Kirsty Kiezebrink and Youl-ri Kim and Kirk, {Katherine M.} and Lars Klareskog and Klump, {Kelly L.} and Knudsen, {Gun Peggy S.} and Mikael Land{\'e}n and Larsen, {Janne T.} and {Le Hellard}, Stephanie and Lepp{\"a}, {Virpi M.} and Dong Li and Paul Lichtenstein and Lisa Lilenfeld and Lin, {Bochao Danae} and Jolanta Lissowska and Astri Lundervold and Jurjen Luykx and Magistretti, {Pierre J.} and Mario Maj and Katrin Mannik and Sara Marsal and Stuber, {Garret D.} and Sullivan, {Patrick F.} and Beata {\'S}wi{\c a}tkowska and Szatkiewicz, {Jin P.} and Ioanna Tachmazidou and Elena Tenconi and Thornton, {Laura M.} and Alfonso Tortorella and Federica Tozzi and Janet Treasure and Artemis Tsitsika and Marta Tyszkiewicz-nwafor and Konstantinos Tziouvas and {Van Elburg}, {Annemarie A.} and {Van Furth}, {Eric F.} and Wade, {Tracey D.} and Gudrun Wagner and Esther Walton and Watson, {Hunna J.} and Thomas Werge and Whiteman, {David C.} and Wichmann, {H. Erich} and Elisabeth Widen and Woodside, {D. Blake} and Shuyang Yao and Zeynep Yilmaz and Eleftheria Zeggini and Stephanie Zerwas and Stephan Zipfel and Witt, {Stephanie H.} and Fabian Streit and Martin Jungkunz and Josef Frank and Swapnil Awasthi and Jens Treutlein and Lydie Dietl and Schwarze, {Cornelia E.} and Norbert Dahmen and Schott, {Bj{\"o}rn H.} and N{\"o}then, {Markus M.} and Stephan Ripke and Arian Mobascher and Dan Rujescu and Klaus Lieb and Stefan Roepke and Christian Schmahl and Martin Bohus and Marcella Rietschel and Silvia Crivelli and Dennis, {Michelle F.} and Harvey, {Phillip D.} and Carter, {Bruce W.} and Huffman, {Jennifer E.} and Daniel Jacobson and Ravi Madduri and Olsen, {Maren K.} and John Pestian and Gaziano, {J. Michael} and Sumitra Muralidhar and Rachel Ramoni and Jean Beckham and Kyong-mi Chang and O{\textquoteright}donnell, {Christopher J.} and Philip Tsao and James Breeling and Grant Huang and Romero, {J.p. Casas} and Sumitra Muralidhar and Jennifer Moser and Whitbourne, {Stacey B.} and Brewer, {Jessica V.} and Mihaela Aslan and Todd Connor and Argyres, {Dean P.} and Philip Tsao and Gaziano, {J. Michael} and Brady Stephens and Brophy, {Mary T.} and Humphries, {Donald E.} and Selva, {Luis E.} and Nhan Do and Shahpoor Shayan and Kelly Cho and O{\textquoteright}donnell, {Christopher J.} and O{\textquoteright}donnell, {Christopher J.} and Saiju Pyarajan and Philip Tsao and Kelly Cho and Saiju Pyarajan and Elizabeth Hauser and Yan Sun and Hongyu Zhao and Peter Wilson and Rachel Mcardle and Louis Dellitalia and Kristin Mattocks and John Harley and Zablocki, {Clement J.} and Jeffrey Whittle and Frank Jacono and Jean Beckham and Salvador Gutierrez and Gretchen Gibson and Kimberly Hammer and Laurence Kaminsky and Gerardo Villareal and Scott Kinlay and Junzhe Xu and Mark Hamner and Roy Mathew and Sujata Bhushan and Pran Iruvanti and Michael Godschalk and Zuhair Ballas and Douglas Ivins and Stephen Mastorides and Jonathan Moorman and Saib Gappy and Jon Klein and Nora Ratcliffe and Hermes Florez and Olaoluwa Okusaga and Maureen Murdoch and Peruvemba Sriram and Yeh, {Shing Shing} and Neeraj Tandon and Darshana Jhala and Samuel Aguayo and David Cohen and Satish Sharma and Suthat Liangpunsakul and Oursler, {Kris Ann} and Mary Whooley and Sunil Ahuja and Joseph Constans and Paul Meyer and Jennifer Greco and Michael Rauchman and Richard Servatius and Melinda Gaddy and Agnes Wallbom and Timothy Morgan and Todd Stapley and Scott Sherman and George Ross and Philip Tsao and Patrick Strollo and Edward Boyko and Laurence Meyer and Samir Gupta and Mostaqul Huq and Joseph Fayad and Adriana Hung and Jack Lichy and Robin Hurley and Brooks Robey and Robert Striker",

year = "2022",

month = feb,

day = "1",

doi = "10.1016/j.biopsych.2021.05.029",

language = "English",

volume = "91",

pages = "313--327",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "3",

}

TY - JOUR

T1 - Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Mullins, Niamh

AU - Kang, Jooeun

AU - Campos, Adrian I.

AU - Coleman, Jonathan R.i.

AU - Edwards, Alexis C.

AU - Galfalvy, Hanga

AU - Levey, Daniel F.

AU - Lori, Adriana

AU - Shabalin, Andrey

AU - Starnawska, Anna

AU - Su, Mei-hsin

AU - Watson, Hunna J.

AU - Adams, Mark

AU - Awasthi, Swapnil

AU - Gandal, Michael

AU - Hafferty, Jonathan D.

AU - Hishimoto, Akitoyo

AU - Kim, Minsoo

AU - Okazaki, Satoshi

AU - Otsuka, Ikuo

AU - Ripke, Stephan

AU - Ware, Erin B.

AU - Bergen, Andrew W.

AU - Berrettini, Wade H.

AU - Bohus, Martin

AU - Brandt, Harry

AU - Chang, Xiao

AU - Chen, Wei J.

AU - Chen, Hsi-chung

AU - Crawford, Steven

AU - Crow, Scott

AU - Diblasi, Emily

AU - Duriez, Philibert

AU - Fernández-aranda, Fernando

AU - Fichter, Manfred M.

AU - Gallinger, Steven

AU - Glatt, Stephen J.

AU - Gorwood, Philip

AU - Guo, Yiran

AU - Hakonarson, Hakon

AU - Halmi, Katherine A.

AU - Hwu, Hai-gwo

AU - Jain, Sonia

AU - Jamain, Stéphane

AU - Jiménez-murcia, Susana

AU - Johnson, Craig

AU - Kaplan, Allan S.

AU - Kaye, Walter H.

AU - Keel, Pamela K.

AU - Kennedy, James L.

AU - Klump, Kelly L.

AU - Li, Dong

AU - Liao, Shih-cheng

AU - Lieb, Klaus

AU - Lilenfeld, Lisa

AU - Liu, Chih-min

AU - Magistretti, Pierre J.

AU - Marshall, Christian R.

AU - Mitchell, James

AU - Monson, Eric T.

AU - Myers, Richard M.

AU - Pinto, Dalila

AU - Powers, Abigail

AU - Ramoz, Nicolas

AU - Roepke, Stefan

AU - Rozanov, Vsevolod

AU - Scherer, Stephen W.

AU - Schmahl, Christian

AU - Sokolowski, Marcus

AU - Strober, Michael

AU - Thornton, Laura M.

AU - Treasure, Janet

AU - Tsuang, Ming T.

AU - Witt, Stephanie H.

AU - Woodside, D. Blake

AU - Yilmaz, Zeynep

AU - Zillich, Lea

AU - Adolfsson, Rolf

AU - Agartz, Ingrid

AU - Air, Tracy M.

AU - Alda, Martin

AU - Alfredsson, Lars

AU - Andreassen, Ole A.

AU - Anjorin, Adebayo

AU - Appadurai, Vivek

AU - Soler Artigas, María

AU - Der Auwera, Sandra Van

AU - Azevedo, M. Helena

AU - Bass, Nicholas

AU - Bau, Claiton H.d.

AU - Baune, Bernhard T.

AU - Bellivier, Frank

AU - Berger, Klaus

AU - Biernacka, Joanna M.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Boehnke, Michael

AU - Boks, Marco P.

AU - Bosch, Rosa

AU - Braff, David L.

AU - Bryant, Richard

AU - Budde, Monika

AU - Byrne, Enda M.

AU - Cahn, Wiepke

AU - Casas, Miguel

AU - Castelao, Enrique

AU - Cervilla, Jorge A.

AU - Chaumette, Boris

AU - Cichon, Sven

AU - Corvin, Aiden

AU - Craddock, Nicholas

AU - Craig, David

AU - Degenhardt, Franziska

AU - Djurovic, Srdjan

AU - Edenberg, Howard J.

AU - Fanous, Ayman H.

AU - Foo, Jerome C.

AU - Forstner, Andreas J.

AU - Frye, Mark

AU - Fullerton, Janice M.

AU - Gatt, Justine M.

AU - Gejman, Pablo V.

AU - Giegling, Ina

AU - Grabe, Hans J.

AU - Green, Melissa J.

AU - Grevet, Eugenio H.

AU - Grigoroiu-serbanescu, Maria

AU - Gutierrez, Blanca

AU - Guzman-parra, Jose

AU - Hamilton, Steven P.

AU - Hamshere, Marian L.

AU - Hartmann, Annette

AU - Hauser, Joanna

AU - Heilmann-heimbach, Stefanie

AU - Hoffmann, Per

AU - Ising, Marcus

AU - Jones, Ian

AU - Jones, Lisa A.

AU - Jonsson, Lina

AU - Kahn, René S.

AU - Kelsoe, John R.

AU - Kendler, Kenneth S.

AU - Kloiber, Stefan

AU - Koenen, Karestan C.

AU - Kogevinas, Manolis

AU - Konte, Bettina

AU - Krebs, Marie-odile

AU - Landén, Mikael

AU - Lawrence, Jacob

AU - Leboyer, Marion

AU - Lee, Phil H.

AU - Levinson, Douglas F.

AU - Liao, Calwing

AU - Lissowska, Jolanta

AU - Lucae, Susanne

AU - Mayoral, Fermin

AU - Mcelroy, Susan L.

AU - Mcgrath, Patrick

AU - Mcguffin, Peter

AU - Mcquillin, Andrew

AU - Medland, Sarah E.

AU - Mehta, Divya

AU - Melle, Ingrid

AU - Milaneschi, Yuri

AU - Mitchell, Philip B.

AU - Molina, Esther

AU - Morken, Gunnar

AU - Mortensen, Preben Bo

AU - Müller-myhsok, Bertram

AU - Nievergelt, Caroline M.

AU - Nimgaonkar, Vishwajit

AU - Nöthen, Markus M.

AU - O’donovan, Michael C.

AU - Ophoff, Roel A.

AU - Owen, Michael J.

AU - Pato, Carlos

AU - Pato, Michele T.

AU - Penninx, Brenda W.j.h.

AU - Pimm, Jonathan

AU - Pistis, Giorgio

AU - Potash, James B.

AU - Power, Robert A.

AU - Preisig, Martin

AU - Quested, Digby

AU - Ramos-quiroga, Josep Antoni

AU - Reif, Andreas

AU - Ribasés, Marta

AU - Richarte, Vanesa

AU - Rietschel, Marcella

AU - Rivera, Margarita

AU - Roberts, Andrea

AU - Roberts, Gloria

AU - Rouleau, Guy A.

AU - Rovaris, Diego L.

AU - Rujescu, Dan

AU - Sánchez-mora, Cristina

AU - Sanders, Alan R.

AU - Schofield, Peter R.

AU - Schulze, Thomas G.

AU - Scott, Laura J.

AU - Serretti, Alessandro

AU - Shi, Jianxin

AU - Shyn, Stanley I.

AU - Sirignano, Lea

AU - Sklar, Pamela

AU - Smeland, Olav B.

AU - Smoller, Jordan W.

AU - Sonuga-barke, Edmund J.s.

AU - Spalletta, Gianfranco

AU - Strauss, John S.

AU - Świątkowska, Beata

AU - Trzaskowski, Maciej

AU - Turecki, Gustavo

AU - Vilar-ribó, Laura

AU - Vincent, John B.

AU - Völzke, Henry

AU - Walters, James T.r.

AU - Shannon Weickert, Cynthia

AU - Weickert, Thomas W.

AU - Weissman, Myrna M.

AU - Williams, Leanne M.

AU - Wray, Naomi R.

AU - Zai, Clement C.

AU - Ashley-koch, Allison E.

AU - Beckham, Jean

AU - Hauser, Elizabeth R.

AU - Hauser, Michael A.

AU - Kimbrel, Nathan A.

AU - Lindquist, Jennifer H.

AU - Mcmahon, Benjamin

AU - Oslin, David W.

AU - Qin, Xuejun

AU - Agerbo, Esben

AU - Børglum, Anders D.

AU - Breen, Gerome

AU - Erlangsen, Annette

AU - Esko, Tõnu

AU - Gelernter, Joel

AU - Hougaard, David M.

AU - Kessler, Ronald C.

AU - Kranzler, Henry R.

AU - Li, Qingqin S.

AU - Martin, Nicholas G.

AU - Mcintosh, Andrew M.

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Olsen, Catherine M.

AU - Porteous, David J.

AU - Ursano, Robert J.

AU - Wasserman, Danuta

AU - Werge, Thomas

AU - Whiteman, David C.

AU - Bulik, Cynthia M.

AU - Coon, Hilary

AU - Demontis, Ditte

AU - Docherty, Anna R.

AU - Kuo, Po-hsiu

AU - Lewis, Cathryn M.

AU - Mann, J. John

AU - Rentería, Miguel E.

AU - Smith, Daniel J.

AU - Stahl, Eli A.

AU - Stein, Murray B.

AU - Streit, Fabian

AU - Willour, Virginia

AU - Ruderfer, Douglas M.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.m.

AU - Bacanu, Silviu-alin

AU - Bækvad-hansen, Marie

AU - Beekman, Aartjan T.f.

AU - Bigdeli, Tim B.

AU - Binder, Elisabeth B.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni-kim

AU - Coleman, Jonathan R.i.

AU - Colodro-conde, Lucía

AU - Couvy-duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-price, Valentina

AU - Hassan Kiadeh, Farnush Farhadi

AU - Finucane, Hilary K.

AU - Foo, Jerome C.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Goes, Fernando S.

AU - Gordon, Scott

AU - Weinsheimer, Shantel Marie

AU - Wellmann, Jürgen

AU - Willemsen, Gonneke

AU - Witt, Stephanie H.

AU - Wu, Yang

AU - Xi, Simon

AU - Yang, Jian

AU - Zhang, Futao

AU - Arolt, Volker

AU - Baune, Bernhard T.

AU - Berger, Klaus

AU - Boomsma, Dorret I.

AU - Cichon, Sven

AU - Dannlowski, Udo

AU - De Geus, E.j.c.

AU - Depaulo, J. Raymond

AU - Domenici, Enrico

AU - Domschke, Katharina

AU - Esko, Tõnu

AU - Grabe, Hans J.

AU - Hamilton, Steven P.

AU - Grove, Jakob

AU - Hall, Lynsey S.

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

AU - Hottenga, Jouke-jan

AU - Hougaard, David M.

AU - Howard, David M.

AU - Ising, Marcus

AU - Jansen, Rick

AU - Jones, Ian

AU - Jones, Lisa A.

AU - Jorgenson, Eric

AU - Knowles, James A.

AU - Kohane, Isaac S.

AU - Kraft, Julia

AU - Kretzschmar, Warren W.

AU - Kutalik, Zoltán

AU - Li, Yihan

AU - Lind, Penelope A.

AU - Macintyre, Donald J.

AU - Mackinnon, Dean F.

AU - Maier, Robert M.

AU - Maier, Wolfgang

AU - Marchini, Jonathan

AU - Mbarek, Hamdi

AU - Mcgrath, Patrick

AU - Mcguffin, Peter

AU - Medland, Sarah E.

AU - Mehta, Divya

AU - Middeldorp, Christel M.

AU - Mihailov, Evelin

AU - Milaneschi, Yuri

AU - Milani, Lili

AU - Mondimore, Francis M.

AU - Montgomery, Grant W.

AU - Mostafavi, Sara

AU - Mullins, Niamh

AU - Nauck, Matthias

AU - Ng, Bernard

AU - Nivard, Michel G.

AU - Nyholt, Dale R.

AU - O’reilly, Paul F.

AU - Oskarsson, Hogni

AU - Hayward, Caroline

AU - Heath, Andrew C.

AU - Kendler, Kenneth S.

AU - Kloiber, Stefan

AU - Lewis, Glyn

AU - Li, Qingqin S.

AU - Lucae, Susanne

AU - Madden, Pamela A.f.

AU - Magnusson, Patrik K.

AU - Martin, Nicholas G.

AU - Mcintosh, Andrew M.

AU - Metspalu, Andres

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Müller-myhsok, Bertram

AU - Nordentoft, Merete

AU - Nöthen, Markus M.

AU - O’donovan, Michael C.

AU - Paciga, Sara A.

AU - Pedersen, Nancy L.

AU - Owen, Michael J.

AU - Painter, Jodie N.

AU - Pedersen, Carsten Bøcker

AU - Pedersen, Marianne Giørtz

AU - Peterson, Roseann E.

AU - Peyrot, Wouter J.

AU - Pistis, Giorgio

AU - Posthuma, Danielle

AU - Quiroz, Jorge A.

AU - Qvist, Per

AU - Rice, John P.

AU - Riley, Brien P.

AU - Rivera, Margarita

AU - Mirza, Saira Saeed

AU - Schoevers, Robert

AU - Schulte, Eva C.

AU - Shen, Ling

AU - Shi, Jianxin

AU - Shyn, Stanley I.

AU - Sigurdsson, Engilbert

AU - Sinnamon, Grant C.b.

AU - Smit, Johannes H.

AU - Smith, Daniel J.

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Tansey, Katherine E.

AU - Teismann, Henning

AU - Teumer, Alexander

AU - Thompson, Wesley

AU - Thomson, Pippa A.

AU - Thorgeirsson, Thorgeir E.

AU - Traylor, Matthew

AU - Treutlein, Jens

AU - Trubetskoy, Vassily

AU - Uitterlinden, André G.

AU - Umbricht, Daniel

AU - Der Auwera, Sandra Van

AU - Van Hemert, Albert M.

AU - Viktorin, Alexander

AU - Visscher, Peter M.

AU - Wang, Yunpeng

AU - Webb, Bradley T.

AU - Penninx, Brenda W.j.h.

AU - Perlis, Roy H.

AU - Porteous, David J.

AU - Potash, James B.

AU - Preisig, Martin

AU - Rietschel, Marcella

AU - Schaefer, Catherine

AU - Schulze, Thomas G.

AU - Smoller, Jordan W.

AU - Stefansson, Kari

AU - Tiemeier, Henning

AU - Uher, Rudolf

AU - Völzke, Henry

AU - Weissman, Myrna M.

AU - Werge, Thomas

AU - Lewis, Cathryn M.

AU - Levinson, Douglas F.

AU - Breen, Gerome

AU - Børglum, Anders D.

AU - Sullivan, Patrick F.

AU - Mullins, Niamh

AU - Forstner, Andreas J.

AU - O’connell, Kevin S.

AU - Coombes, Brandon

AU - Coleman, Jonathan R.i.

AU - Qiao, Zhen

AU - Als, Thomas D.

AU - Bigdeli, Tim B.

AU - Børte, Sigrid

AU - Bryois, Julien

AU - Charney, Alexander W.

AU - Drange, Ole Kristian

AU - Gandal, Michael J.

AU - Hagenaars, Saskia P.

AU - Ikeda, Masashi

AU - Kamitaki, Nolan

AU - Kim, Minsoo

AU - Krebs, Kristi

AU - Panagiotaropoulou, Georgia

AU - Schilder, Brian M.

AU - Sloofman, Laura G.

AU - Steinberg, Stacy

AU - Trubetskoy, Vassily

AU - Winsvold, Bendik S.

AU - Won, Hong-hee

AU - Abramova, Liliya

AU - Adorjan, Kristina

AU - Agerbo, Esben

AU - Al Eissa, Mariam

AU - Albani, Diego

AU - Alliey-rodriguez, Ney

AU - Anjorin, Adebayo

AU - Antilla, Verneri

AU - Antoniou, Anastasia

AU - Awasthi, Swapnil

AU - Baek, Ji Hyun

AU - Bækvad-hansen, Marie

AU - Bass, Nicholas

AU - Bauer, Michael

AU - Beins, Eva C.

AU - Bergen, Sarah E.

AU - Birner, Armin

AU - Pedersen, Carsten Bøcker

AU - Bøen, Erlend

AU - Boks, Marco P.

AU - Bosch, Rosa

AU - Brum, Murielle

AU - Brumpton, Ben M.

AU - Brunkhorst-kanaan, Nathalie

AU - Budde, Monika

AU - Bybjerg-grauholm, Jonas

AU - Byerley, William

AU - Cairns, Murray

AU - Casas, Miquel

AU - Cervantes, Pablo

AU - Clarke, Toni-kim

AU - Cruceanu, Cristiana

AU - Cuellar-barboza, Alfredo

AU - Cunningham, Julie

AU - Curtis, David

AU - Czerski, Piotr M.

AU - Dale, Anders M.

AU - Dalkner, Nina

AU - David, Friederike S.

AU - Degenhardt, Franziska

AU - Djurovic, Srdjan

AU - Dobbyn, Amanda L.

AU - Douzenis, Athanassios

AU - Elvsåshagen, Torbjørn

AU - Escott-price, Valentina

AU - Ferrier, I. Nicol

AU - Fiorentino, Alessia

AU - Foroud, Tatiana M.

AU - Forty, Liz

AU - Frank, Josef

AU - Frei, Oleksandr

AU - Freimer, Nelson B.

AU - Frisén, Louise

AU - Gade, Katrin

AU - Garnham, Julie

AU - Gelernter, Joel

AU - Pedersen, Marianne Giørtz

AU - Gizer, Ian R.

AU - Gordon, Scott

AU - Gordon-smith, Katherine

AU - Greenwood, Tiffany A.

AU - Grove, Jakob

AU - Guzman-parra, José

AU - Ha, Kyooseob

AU - Haraldsson, Magnus

AU - Hautzinger, Martin

AU - Heilbronner, Urs

AU - Hellgren, Dennis

AU - Herms, Stefan

AU - Hoffmann, Per

AU - Holmans, Peter A.

AU - Huckins, Laura M.

AU - Jamain, Stéphane

AU - Johnson, Jessica S.

AU - Kalman, Janos L.

AU - Kamatani, Yoichiro

AU - Kennedy, James L.

AU - Kittel-schneider, Sarah

AU - Knowles, James A.

AU - Kogevinas, Manolis

AU - Koromina, Maria

AU - Kranz, Thorsten M.

AU - Kranzler, Henry R.

AU - Kubo, Michiaki

AU - Kupka, Ralph

AU - Kushner, Steven A.

AU - Lavebratt, Catharina

AU - Lawrence, Jacob

AU - Leber, Markus

AU - Lee, Heon-jeong

AU - Lee, Phil H.

AU - Levy, Shawn E.

AU - Lewis, Catrin

AU - Liao, Calwing

AU - Lucae, Susanne

AU - Lundberg, Martin

AU - Macintyre, Donald J.

AU - Magnusson, Sigurdur H.

AU - Maier, Wolfgang

AU - Maihofer, Adam

AU - Malaspina, Dolores

AU - Maratou, Eirini

AU - Martinsson, Lina

AU - Mattheisen, Manuel

AU - Mcgregor, Nathaniel W.

AU - Mcguffin, Peter

AU - Mckay, James D.

AU - Medeiros, Helena

AU - Medland, Sarah E.

AU - Millischer, Vincent

AU - Montgomery, Grant W.

AU - Moran, Jennifer L.

AU - Morris, Derek W.

AU - Mühleisen, Thomas W.

AU - O’brien, Niamh

AU - O’donovan, Claire

AU - Olde Loohuis, Loes M.

AU - Oruc, Lilijana

AU - Papiol, Sergi

AU - Pardiñas, Antonio F.

AU - Perry, Amy

AU - Pfennig, Andrea

AU - Porichi, Evgenia

AU - Potash, James B.

AU - Quested, Digby

AU - Raj, Towfique

AU - Rapaport, Mark H.

AU - Depaulo, J. Raymond

AU - Regeer, Eline J.

AU - Rice, John P.

AU - Rivas, Fabio

AU - Rivera, Margarita

AU - Roth, Julian

AU - Roussos, Panos

AU - Ruderfer, Douglas M.

AU - Sánchez-mora, Cristina

AU - Schulte, Eva C.

AU - Senner, Fanny

AU - Sharp, Sally

AU - Shilling, Paul D.

AU - Sigurdsson, Engilbert

AU - Sirignano, Lea

AU - Slaney, Claire

AU - Smeland, Olav B.

AU - Smith, Daniel J.

AU - Sobell, Janet L.

AU - Hansen, Christine Søholm

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AU - Striker, Robert

PY - 2022/2/1

Y1 - 2022/2/1

N2 - 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.

AB - 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.

KW - Genetic correlation

KW - Genome-wide association study

KW - Pleiotropy

KW - Polygenicity

KW - Suicide

KW - Suicide attempt

UR - http://www.scopus.com/inward/record.url?scp=85119273569&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2021.05.029

DO - 10.1016/j.biopsych.2021.05.029

M3 - Article

C2 - 34861974

SN - 0006-3223

VL - 91

SP - 313

EP - 327

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 3

ER -

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

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