Faculty, Staff and Student Publications

Language

English

Publication Date

10-1-2023

Journal

American Journal of Psychiatry

DOI

10.1176/appi.ajp.21121266

PMID

37777856

PMCID

PMC10603363

PubMedCentral® Posted Date

10-27-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

OBJECTIVE: 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.

METHODS: 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.

RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values < 5×10

CONCLUSIONS: 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, Risk Factors, Suicidal Ideation, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genetic Loci

Published Open-Access

yes

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