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

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 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.

Déclaration de conflit d'intérêts

Dr. Campos is an employee of Regeneron Pharmaceuticals and may own stock or stock options. Dr. Kranzler has served as an advisory board member for Clearmind Medicine, Dicerna Pharmaceuticals, Enthion Pharmaceuticals, and Sophrosyne Pharmaceuticals and as a consultant for Sobrera Pharmaceuticals; he has received research funding and medication supplies for an investigator-initiated study from Alkermes; he is a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which was supported in the past 3 years by Alkermes, Dicerna, Ethypharm, Lundbeck, Mitsubishi, Otsuka, and Pear Therapeutics; and he is a holder of U.S. patent 10,900,082 (“Genotype-guided dosing of opioid agonists”). Dr. Andreassen has served as national principal investigator for clinical trials sponsored by BI, Janssen, and MAPS; he has served as a consultant for Cortechs.ai and as a speaker for Janssen, Lundbeck, and Sunovion. Dr. Bulik has received grant support from Lundbeckfonden and royalties from Pearson, and she serves as a stakeholder advisory board member for Equip Health. Dr. Kessler has served as a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, RallyPoint Networks, and Sage Therapeutics, and he has stock options in Cerebral, Mirah, PYM, Roga Sciences, and Verisense Health. Dr. Mann receives royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene. Dr. Polimanti has received a research grant from Alkermes and is co-editor-in-chief of