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Mullins, N.* ; Kang, J.E.* ; Campos, A.I.* ; Coleman, J.R.I.* ; Edwards, A.C.* ; Galfalvy, H.* ; Levey, D.F.* ; Lori, A.* ; Shabalin, A.A.* ; Starnawska, A.* ; Su, M.H.* ; Watson, H.J.* ; Adams, M.* ; Awasthi, S.* ; Gandal, M.* ; Hafferty, J.D.* ; Hishimoto, A.* ; Kim, M.* ; Okazaki, S.* ; Otsuka, I.* ; Ripke, S.* ; Ware, E.B.* ; Bergen, A.W.* ; Berrettini, W.H.* ; Bohus, M.* ; Brandt, H.* ; Chang, X.* ; Chen, W.J.* ; Chen, H.C.* ; Crawford, S.* ; Crow, S.* ; DiBlasi, E.* ; Duriez, P.* ; Fernández-Aranda, F.* ; Fichter, M.M.* ; Gallinger, S.* ; Glatt, S.J.* ; Gorwood, P.* ; Guo, Y.* ; Hakonarson, H.* ; Halmi, K.A.* ; Hwu, H.G.* ; Jain, S.* ; Jamain, S.* ; Jiménez-Murcia, S.* ; Johnson, C.* ; Kaplan, A.S.* ; Kaye, W.H.* ; Keel, P.K.* ; Kennedy, J.L.* ; Klump, K.L.* ; Li, D.* ; Liao, S.C.* ; Lieb, K.* ; Lilenfeld, L.* ; Liu, C.M.* ; Magistretti, P.J.* ; Marshall, C.R.* ; Mitchell, J.E.* ; Monson, E.T.* ; Myers, R.M.* ; Pinto, D.* ; Powers, A.C.* ; Ramoz, N.* ; Roepke, S.* ; Rozanov, V.* ; Scherer, S.W.* ; Schmahl, C.* ; Sokolowski, M.* ; Strober, M.* ; Thornton, L.M.* ; Treasure, J.* ; Tsuang, M.T.* ; Witt, S.H.* ; Woodside, D.B.* ; Yilmaz, Z.* ; Zillich, L.* ; Adolfsson, R.* ; Agartz, I.* ; Air, T.M.* ; Alda, M.* ; Alfredsson, L.* ; Andreassen, O.A.* ; Anjorin, A.* ; Appadurai, V.* ; Soler Artigas, M.* ; Van der Auwera, S.* ; Azevedo, M.H.* ; Bass, N.J.* ; Bau, C.H.D.* ; Baune, B.T.* ; Bellivier, F.* ; Berger, K.* ; Biernacka, J.M.* ; Bigdeli, T.B.* ; Binder, E.B.* ; Boehnke, M.* ; Boks, M.P.* ; Bosch, R.* ; Braff, D.L.* ; Streit, F.* ; Willour, V.* ; Ruderfer, D.* ; Eating Disorders Working Group of the Psychiatric Genomics Consortium (Hatzikotoulas, K. ; Zeggini, E. ; Wichmann, H.-E. ; Jablensky, A.V.)

Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders, and known risk factors.

Biol. Psychiatry 91, 313-327 (2022)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Genetic Correlation ; Genome-wide Association Study ; Pleiotropy ; Polygenicity ; Suicide ; Suicide Attempt
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 0006-3223
e-ISSN 1873-2402
Journal Biological Psychiatry
Quellenangaben Volume: 91, Issue: 3, Pages: 313-327 Article Number: , Supplement: ,
Publisher Elsevier
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-506700-001
Grants Janssen Pharmaceuticals
Fresenius Medical Care North America
Takeda Pharmaceutical Company
National Institutes of Health
Mount Sinai high performance computing cluster
National Institute of General Medical Sciences
Brain and Behavior Research Foundation
National Alliance for Research on Schizophrenia and Depression
DOI 10.1016/j.biopsych.2021.05.029
Scopus ID 85119273569
Erfassungsdatum 2022-10-28
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