Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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AuthorMullins, Niamh; Cervilla Ballesteros, Jorge Antonio; Gutiérrez Martínez, Blanca; Molina Rivas, Esther; Rivera Sánchez, Margarita; Psychiat Genomics Consortium; German Borderline Genomics Consort; MVP Suicide Exemplar Workgrp; VA Million Vet Program
Mullins, N... [et al.]. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors, Biological Psychiatry, Volume 91, Issue 3, 2022, Pages 313-327, ISSN 0006-3223, [https://doi.org/10.1016/j.biopsych.2021.05.029]
SponsorshipOffice of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01MH116269 R01MH121455; United States Department of Health & Human Services; NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
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.