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

Mullins, Niamh, Kang, Jooeun, Campos, Adrian I., Craddock, Nick ORCID: https://orcid.org/0000-0003-2171-0610, Hamshere, Marian L. ORCID: https://orcid.org/0000-0002-8990-0958, Jones, Ian ORCID: https://orcid.org/0000-0001-5821-5889, O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862 and Walters, James T.R. ORCID: https://orcid.org/0000-0002-6980-4053 2022. Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors. Biological Psychiatry 91 (3) , pp. 313-327. 10.1016/j.biopsych.2021.05.029

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Abstract

Background Suicide is a leading cause of death worldwide, and non-fatal 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. The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via mtCOJO, 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, 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, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking, 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 non-psychiatric 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
Publisher:	Elsevier
ISSN:	0006-3223
Date of First Compliant Deposit:	31 August 2021
Date of Acceptance:	26 May 2021
Last Modified:	07 May 2023 01:32
URI:	https://orca.cardiff.ac.uk/id/eprint/143773

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