Genome-wide association study identifies four pan-ancestry loci for suicidal ideation in the Million Veteran Program

Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other sui...

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Bibliographic Details
Published in:PLoS genetics 2023-03, Vol.19 (3), p.e1010623
Main Authors: Ashley-Koch, Allison E, Kimbrel, Nathan A, Qin, Xue J, Lindquist, Jennifer H, Garrett, Melanie E, Dennis, Michelle F, Hair, Lauren P, Huffman, Jennifer E, Jacobson, Daniel A, Madduri, Ravi K, Coon, Hilary, Docherty, Anna R, Kang, Jooeun, Mullins, Niamh, Ruderfer, Douglas M, Harvey, Philip D, McMahon, Benjamin H, Oslin, David W, Hauser, Elizabeth R, Hauser, Michael A, Beckham, Jean C
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Care and treatment
Chromosomes
Comorbidity
Depressive Disorder, Major - genetics
Development and progression
Diagnosis
Dopamine D2 receptors
Electronic health records
Electronic medical records
Genetic diversity
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Humans
Medical records
Medicin och hälsovetenskap
Medicine and Health Sciences
Mental depression
Mental disorders
Meta-analysis
Methods
Phenotypes
Post traumatic stress disorder
Prevention
Risk Factors
Startle response
Suicidal behavior
Suicidal Ideation
Suicide
Suicide, Attempted - psychology
Veterans
Veterans - psychology
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Summary:Suicidal ideation (SI) often precedes and predicts suicide attempt and death, is the most common suicidal phenotype and is over-represented in veterans. The genetic architecture of SI in the absence of suicide attempt (SA) is unknown, yet believed to have distinct and overlapping risk with other suicidal behaviors. We performed the first GWAS of SI without SA in the Million Veteran Program (MVP), identifying 99,814 SI cases from electronic health records without a history of SA or suicide death (SD) and 512,567 controls without SI, SA or SD. GWAS was performed separately in the four largest ancestry groups, controlling for sex, age and genetic substructure. Ancestry-specific results were combined via meta-analysis to identify pan-ancestry loci. Four genome-wide significant (GWS) loci were identified in the pan-ancestry meta-analysis with loci on chromosomes 6 and 9 associated with suicide attempt in an independent sample. Pan-ancestry gene-based analysis identified GWS associations with DRD2, DCC, FBXL19, BCL7C, CTF1, ANNK1, and EXD3. Gene-set analysis implicated synaptic and startle response pathways (q's
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1010623