Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.
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State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_EEE7BFFEF014
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.
Journal
Biological psychiatry
Working group(s)
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Eating Disorders Working Group of the Psychiatric Genomics Consortium, German Borderline Genomics Consortium, MVP Suicide Exemplar Workgroup, VA Million Veteran Program, Hunt All-In Psychiatry
Contributor(s)
Wray N.R., Ripke S., Mattheisen M., Trzaskowski M., Byrne E.M., Abdellaoui A., Adams M.J., Agerbo E., Air T.M., Andlauer TFM, Bacanu S.A., Bækvad-Hansen M., Beekman ATF, Bigdeli T.B., Binder E.B., Bryois J., Buttenschøn H.N., Bybjerg-Grauholm J., Cai N., Castelao E., Christensen J.H., Clarke T.K., Coleman JRI, Colodro-Conde L., Couvy-Duchesne B., Craddock N., Crawford G.E., Davies G., Degenhardt F., Derks E.M., Direk N., Dolan C.V., Dunn E.C., Eley T.C., Escott-Price V., Hassan Kiadeh F.F., Finucane H.K., Foo J.C., Forstner A.J., Frank J., Gaspar H.A., Gill M., Goes F.S., Gordon S.D., Weinsheimer S.M., Wellmann J., Willemsen G., Witt S.H., Wu Y., Xi H.S., Yang J., Zhang F., Arolt V., Baune B.T., Berger K., Boomsma D.I., Cichon S., Dannlowski U., de Geus EJC, Depaulo J.R., Domenici E., Domschke K., Esko T., Grabe H.J., Hamilton S.P., Grove J., Hall L.S., Hansen C.S., Hansen T.F., Herms S., Hickie I.B., Hoffmann P., Homuth G., Horn C., Hottenga J.J., Hougaard D.M., Howard D.M., Ising M., Jansen R., Jones I., Jones L.A., Jorgenson E., Knowles J.A., Kohane I.S., Kraft J., Kretzschmar W.W., Kutalik Z., Li Y., Lind P.A., MacIntyre D.J., MacKinnon D.F., Maier R.M., Maier W., Marchini J., Mbarek H., McGrath P., McGuffin P., Medland S.E., Mehta D., Middeldorp C.M., Mihailov E., Milaneschi Y., Milani L., Mondimore F.M., Montgomery G.W., Mostafavi S., Mullins N., Nauck M., Ng B., Nivard M.G., Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Kendler K.S., Kloiber S., Lewis G., Li Q.S., Lucae S., Madden PAF, Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Mortensen P.B., Müller-Myhsok B., Nordentoft M., Nöthen M.M., O'Donovan M.C., Paciga S.A., Pedersen N.L., Owen M.J., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Pistis G., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Rivera M., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Shi J., Shyn S.I., Sigurdsson E., Sinnamon GCB, Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Penninx BWJH, Perlis R.H., Porteous D.J., Potash J.B., Preisig M., Rietschel M., Schaefer C., Schulze T.G., Smoller J.W., Stefansson K., Tiemeier H., Uher R., Völzke H., Weissman M.M., Werge T., Lewis C.M., Levinson D.F., Breen G., Børglum A.D., Sullivan P.F., Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman JRI, Qiao Z., Als T.D., Bigdeli T.B., Børte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Bækvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Pedersen C.B., Bøen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsåshagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisén L., Gade K., Garnham J., Gelernter J., Pedersen M.G., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Mühleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardiñas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sánchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Hansen C.S., Artigas M.S., Spijker A.T., Stein D.J., Strauss J.S., Świątkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.E., Vawter M.P., Vedder H., Walters JTR, Witt S.H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood DHR, Boehnke M., Børglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landén M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Müller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nöthen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribasés M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Weickert C.S., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., Adan RAH, Alfredsson L., Ando T., Andreassen O.A., Aschauer H., Baker J.H., Bencko V., Bergen A.W., Berrettini W.H., Birgegård A., Boden J.M., Boehm I., Boni C., Perica V.B., Brandt H., Breen G., Bryois J., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Cichon S., Clementi M., Coleman JRI, Cone R.D., Courtet P., Crawford S., Crow S., Crowley J.J., Danner U.N., Davis OSP, de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dikeos D., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Marshall C.R., Martin N.G., Mattheisen M., Mattingsdal M., McDevitt S., McGuffin P., Medland S.E., Metspalu A., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Montgomery G.W., Mortensen P.B., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., Ophoff R.A., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Pedersen N.L., Ehrlich S., Escaramís G., Esko T., Espeseth T., Estivill X., Farmer A., Favaro A., Fernández-Aranda F., Fichter M.M., Fischer K., Floyd JAB, Föcker M., Foretova L., Forstner A.J., Forzan M., Franklin C.S., Gallinger S., Gambaro G., Gaspar H.A., Giegling I., Giuranna J., Giusti-Rodríquez P., Gonidakis F., Gordon S., Gorwood P., Mayora M.G., Grove J., Guillaume S., Guo Y., Hakonarson H., Halmi K.A., Hanscombe K.B., Hatzikotoulas K., Hauser J., Hebebrand J., Helder S.G., Henders A.K., Herms S., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hübel C., Petersen L.V., Pinto D., Purves K.L., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ripke S., Ritschel F., Roberts M., Rujescu D., Rybakowski F., Santonastaso P., Scherag A., Scherer S.W., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt MCT, Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Strober M., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jiménez-Murcia S., Johnson C., Jordan J., Julià A., Kalsi G., Kaminská D., Kaplan A.S., Kaprio J., Karhunen L., Karwautz A., Kas MJH, Kaye W.H., Kennedy J.L., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.R., Kirk K.M., Klareskog L., Klump K.L., Knudsen GPS, Landén M., Larsen J.T., Le Hellard S., Leppä V.M., Li D., Lichtenstein P., Lilenfeld L., Lin B.D., Lissowska J., Lundervold A., Luykx J., Magistretti P.J., Maj M., Mannik K., Marsal S., Stuber G.D., Sullivan P.F., Świątkowska B., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Thornton L.M., Tortorella A., Tozzi F., Treasure J., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Watson H.J., Werge T., Whiteman D.C., Wichmann H.E., Widen E., Woodside D.B., Yao S., Yilmaz Z., Zeggini E., Zerwas S., Zipfel S., Witt S.H., Streit F., Jungkunz M., Frank J., Awasthi S., Treutlein J., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Nöthen M.M., Ripke S., Mobascher A., Rujescu D., Lieb K., Roepke S., Schmahl C., Bohus M., Rietschel M., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero JPC, Muralidhar S., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Tsao P.S., Gaziano J.M., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., O'Donnell C.J., O'Donnell C.J., Pyarajan S., Tsao P.S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Beckham J., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R.
ISSN
1873-2402 (Electronic)
ISSN-L
0006-3223
Publication state
Published
Issued date
01/02/2022
Peer-reviewed
Oui
Volume
91
Number
3
Pages
313-327
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
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.
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.
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.
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.
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
Depressive Disorder, Major/genetics, Genome-Wide Association Study, Humans, Mental Disorders/genetics, Polymorphism, Single Nucleotide, Risk Factors, Suicide, Attempted, Genetic correlation, Genome-wide association study, Pleiotropy, Polygenicity, Suicide, Suicide attempt
Pubmed
Web of science
Open Access
Yes
Create date
04/02/2022 18:36
Last modification date
25/01/2024 7:47
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