GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

Docherty, A.R.; Mullins, N.; Ashley-Koch, A.E.; Qin, X.; Coleman, JRI; Shabalin, A.; Kang, J.; Murnyak, B.; Wendt, F.; Adams, M.; Campos, A.I.; DiBlasi, E.; Fullerton, J.M.; Kranzler, H.R.; Bakian, A.V.; Monson, E.T.; Rentería, M.E.; Walss-Bass, C.; Andreassen, O.A.; Behera, C.; Bulik, C.M.; Edenberg, H.J.; Kessler, R.C.; Mann, J.J.; Nurnberger, J.I.; Pistis, G.; Streit, F.; Ursano, R.J.; Polimanti, R.; Dennis, M.; Garrett, M.; Hair, L.; Harvey, P.; Hauser, E.R.; Hauser, M.A.; Huffman, J.; Jacobson, D.; Madduri, R.; McMahon, B.; Oslin, D.W.; Trafton, J.; Awasthi, S.; Berrettini, W.H.; Bohus, M.; Chang, X.; Chen, H.C.; Chen, W.J.; Christensen, E.D.; Crow, S.; Duriez, P.; Edwards, A.C.; Fernández-Aranda, F.; Galfalvy, H.; Gandal, M.; Gorwood, P.; Guo, Y.; Hafferty, J.D.; Hakonarson, H.; Halmi, K.A.; Hishimoto, A.; Jain, S.; Jamain, S.; Jiménez-Murcia, S.; Johnson, C.; Kaplan, A.S.; Kaye, W.H.; Keel, P.K.; Kennedy, J.L.; Kim, M.; Klump, K.L.; Levey, D.F.; Li, D.; Liao, S.C.; Lieb, K.; Lilenfeld, L.; Marshall, C.R.; Mitchell, J.E.; Okazaki, S.; Otsuka, I.; Pinto, D.; Powers, A.; Ramoz, N.; Ripke, S.; Roepke, S.; Rozanov, V.; Scherer, S.W.; Schmahl, C.; Sokolowski, M.; Starnawska, A.; Strober, M.; Su, M.H.; Thornton, L.M.; Treasure, J.; Ware, E.B.; Watson, H.J.; Witt, S.H.; Woodside, D.B.; Yilmaz, Z.; Zillich, L.; Adolfsson, R.; Agartz, I.; Alda, M.; Alfredsson, L.; Appadurai, V.; Artigas, M.S.; Van der Auwera, S.; Azevedo, M.H.; Bass, N.; Bau, CHD; Baune, B.T.; Bellivier, F.; Berger, K.; Biernacka, J.M.; Bigdeli, T.B.; Binder, E.B.; Boehnke, M.; Boks, M.P.; Braff, D.L.; Bryant, R.; Budde, M.; Byrne, E.M.; Cahn, W.; Castelao, E.; Cervilla, J.A.; Chaumette, B.; Corvin, A.; Craddock, N.; Djurovic, S.; Foo, J.C.; Forstner, A.J.; Frye, M.; Gatt, J.M.; Giegling, I.; Grabe, H.J.; Green, M.J.; Grevet, E.H.; Grigoroiu-Serbanescu, M.; Gutierrez, B.; Guzman-Parra, J.; Hamshere, M.L.; Hartmann, A.M.; Hauser, J.; Heilmann-Heimbach, S.; Hoffmann, P.; Ising, M.; Jones, I.; Jones, L.A.; Jonsson, L.; Kahn, R.S.; Kelsoe, J.R.; Kendler, K.S.; Kloiber, S.; Koenen, K.C.; Kogevinas, M.; Krebs, M.O.; Landén, M.; Leboyer, M.; Lee, P.H.; Levinson, D.F.; Liao, C.; Lissowska, J.; Mayoral, F.; McElroy, S.L.; McGrath, P.; McGuffin, P.; McQuillin, A.; Mehta, D.; Melle, I.; Mitchell, P.B.; Molina, E.; Morken, G.; Nievergelt, C.; Nöthen, M.M.; O'Donovan, M.C.; Ophoff, R.A.; Owen, M.J.; Pato, C.; Pato, M.T.; Penninx, BWJH; Potash, J.B.; Power, R.A.; Preisig, M.; Quested, D.; Ramos-Quiroga, J.A.; Reif, A.; Ribasés, M.; Richarte, V.; Rietschel, M.; Rivera, M.; Roberts, A.; Roberts, G.; Rouleau, G.A.; Rovaris, D.L.; Sanders, A.R.; Schofield, P.R.; Schulze, T.G.; Scott, L.J.; Serretti, A.; Shi, J.; Sirignano, L.; Sklar, P.; Smeland, O.B.; Smoller, J.W.; Sonuga-Barke, EJS; Trzaskowski, M.; Tsuang, M.T.; Turecki, G.; Vilar-Ribó, L.; Vincent, J.B.; Völzke, H.; Walters, JTR; Weickert, C.S.; Weickert, T.W.; Weissman, M.M.; Williams, L.M.; Wray, N.R.; Zai, C.C.; Agerbo, E.; Børglum, A.D.; Breen, G.; Demontis, D.; Erlangsen, A.; Gelernter, J.; Glatt, S.J.; Hougaard, D.M.; Hwu, H.G.; Kuo, P.H.; Lewis, C.M.; Li, Q.S.; Liu, C.M.; Martin, N.G.; McIntosh, A.M.; Medland, S.E.; Mors, O.; Nordentoft, M.; Olsen, C.M.; Porteous, D.; Smith, D.J.; Stahl, E.A.; Stein, M.B.; Wasserman, D.; Werge, T.; Whiteman, D.C.; Willour, V.; Coon, H.; Beckham, J.C.; Kimbrel, N.A.; Ruderfer, D.M.

doi:10.1176/appi.ajp.21121266

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

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Serval ID

serval:BIB_B439E586D149

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

Journal

The American journal of psychiatry

Author(s)

Docherty A.R., Mullins N., Ashley-Koch A.E., Qin X., Coleman JRI, Shabalin A., Kang J., Murnyak B., Wendt F., Adams M., Campos A.I., DiBlasi E., Fullerton J.M., Kranzler H.R., Bakian A.V., Monson E.T., Rentería M.E., Walss-Bass C., Andreassen O.A., Behera C., Bulik C.M., Edenberg H.J., Kessler R.C., Mann J.J., Nurnberger J.I., Pistis G., Streit F., Ursano R.J., Polimanti R., Dennis M., Garrett M., Hair L., Harvey P., Hauser E.R., Hauser M.A., Huffman J., Jacobson D., Madduri R., McMahon B., Oslin D.W., Trafton J., Awasthi S., Berrettini W.H., Bohus M., Chang X., Chen H.C., Chen W.J., Christensen E.D., Crow S., Duriez P., Edwards A.C., Fernández-Aranda F., Galfalvy H., Gandal M., Gorwood P., Guo Y., Hafferty J.D., Hakonarson H., Halmi K.A., Hishimoto A., Jain S., Jamain S., Jiménez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Kim M., Klump K.L., Levey D.F., Li D., Liao S.C., Lieb K., Lilenfeld L., Marshall C.R., Mitchell J.E., Okazaki S., Otsuka I., Pinto D., Powers A., Ramoz N., Ripke S., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Starnawska A., Strober M., Su M.H., Thornton L.M., Treasure J., Ware E.B., Watson H.J., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Appadurai V., Artigas M.S., Van der Auwera S., Azevedo M.H., Bass N., Bau CHD, Baune B.T., Bellivier F., Berger K., Biernacka J.M., Bigdeli T.B., Binder E.B., Boehnke M., Boks M.P., Braff D.L., Bryant R., Budde M., Byrne E.M., Cahn W., Castelao E., Cervilla J.A., Chaumette B., Corvin A., Craddock N., Djurovic S., Foo J.C., Forstner A.J., Frye M., Gatt J.M., Giegling I., Grabe H.J., Green M.J., Grevet E.H., Grigoroiu-Serbanescu M., Gutierrez B., Guzman-Parra J., Hamshere M.L., Hartmann A.M., Hauser J., Heilmann-Heimbach S., Hoffmann P., Ising M., Jones I., Jones L.A., Jonsson L., Kahn R.S., Kelsoe J.R., Kendler K.S., Kloiber S., Koenen K.C., Kogevinas M., Krebs M.O., Landén M., Leboyer M., Lee P.H., Levinson D.F., Liao C., Lissowska J., Mayoral F., McElroy S.L., McGrath P., McGuffin P., McQuillin A., Mehta D., Melle I., Mitchell P.B., Molina E., Morken G., Nievergelt C., Nöthen M.M., O'Donovan M.C., Ophoff R.A., Owen M.J., Pato C., Pato M.T., Penninx BWJH, Potash J.B., Power R.A., Preisig M., Quested D., Ramos-Quiroga J.A., Reif A., Ribasés M., Richarte V., Rietschel M., Rivera M., Roberts A., Roberts G., Rouleau G.A., Rovaris D.L., Sanders A.R., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Shi J., Sirignano L., Sklar P., Smeland O.B., Smoller J.W., Sonuga-Barke EJS, Trzaskowski M., Tsuang M.T., Turecki G., Vilar-Ribó L., Vincent J.B., Völzke H., Walters JTR, Weickert C.S., Weickert T.W., Weissman M.M., Williams L.M., Wray N.R., Zai C.C., Agerbo E., Børglum A.D., Breen G., Demontis D., Erlangsen A., Gelernter J., Glatt S.J., Hougaard D.M., Hwu H.G., Kuo P.H., Lewis C.M., Li Q.S., Liu C.M., Martin N.G., McIntosh A.M., Medland S.E., Mors O., Nordentoft M., Olsen C.M., Porteous D., Smith D.J., Stahl E.A., Stein M.B., Wasserman D., Werge T., Whiteman D.C., Willour V., Coon H., Beckham J.C., Kimbrel N.A., Ruderfer D.M.

Working group(s)

VA Million Veteran Program (MVP), MVP Suicide Exemplar Workgroup, Suicide Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Eating Disorder Working Group of the Psychiatric Genomics Consortium, German Borderline Genomics Consortium

ISSN

1535-7228 (Electronic)

ISSN-L

0002-953X

Publication state

Published

Issued date

01/10/2023

Peer-reviewed

Oui

Volume

180

Number

Pages

723-738

Language

english

Notes

Publication types: Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish

Abstract

Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.
This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.
Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10 <sup>-8</sup> . These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10 <sup>-80</sup> ). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.
This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Keywords

Humans, Genome-Wide Association Study, Suicide, Attempted, Depressive Disorder, Major/genetics, Risk Factors, Suicidal Ideation, Polymorphism, Single Nucleotide/genetics, Genetic Predisposition to Disease/genetics, Genetic Loci/genetics, Biological Markers, Depressive Disorders, Genetics, Schizophrenia Spectrum and Other Psychotic Disorders, Self-Harm, Suicide

OAI-PMH

oai:serval.unil.ch:BIB_B439E586D149

DOI

10.1176/appi.ajp.21121266

Pubmed

37777856

Create date

06/10/2023 14:49

Last modification date

19/12/2023 8:15

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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

Details