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A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.

Publication ,  Journal Article
Kimbrel, NA; Ashley-Koch, AE; Qin, XJ; Lindquist, JH; Garrett, ME; Dennis, MF; Hair, LP; Huffman, JE; Jacobson, DA; Madduri, RK; Trafton, JA ...
Published in: Mol Psychiatry
April 2022

To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR (N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 (p = 3.64 × 10-9) and 1 (p = 3.69 × 10-8). A strong pan-ancestry signal at the Dopamine Receptor D2 locus (p = 1.77 × 10-7) was also identified and subsequently replicated in a large, independent international civilian cohort (p = 7.97 × 10-4). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested over-representation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.

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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

April 2022

Volume

27

Issue

4

Start / End Page

2264 / 2272

Location

England

Related Subject Headings

  • White People
  • Veterans
  • Suicide, Attempted
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Black or African American
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kimbrel, N. A., Ashley-Koch, A. E., Qin, X. J., Lindquist, J. H., Garrett, M. E., Dennis, M. F., … Beckham, J. C. (2022). A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci. Mol Psychiatry, 27(4), 2264–2272. https://doi.org/10.1038/s41380-022-01472-3
Kimbrel, Nathan A., Allison E. Ashley-Koch, Xue J. Qin, Jennifer H. Lindquist, Melanie E. Garrett, Michelle F. Dennis, Lauren P. Hair, et al. “A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.Mol Psychiatry 27, no. 4 (April 2022): 2264–72. https://doi.org/10.1038/s41380-022-01472-3.
Kimbrel NA, Ashley-Koch AE, Qin XJ, Lindquist JH, Garrett ME, Dennis MF, et al. A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci. Mol Psychiatry. 2022 Apr;27(4):2264–72.
Kimbrel, Nathan A., et al. “A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.Mol Psychiatry, vol. 27, no. 4, Apr. 2022, pp. 2264–72. Pubmed, doi:10.1038/s41380-022-01472-3.
Kimbrel NA, Ashley-Koch AE, Qin XJ, Lindquist JH, Garrett ME, Dennis MF, Hair LP, Huffman JE, Jacobson DA, Madduri RK, Trafton JA, Coon H, Docherty AR, Kang J, Mullins N, Ruderfer DM, VA Million Veteran Program (MVP), MVP Suicide Exemplar Workgroup, International Suicide Genetics Consortium, Harvey PD, McMahon BH, Oslin DW, Hauser ER, Hauser MA, Beckham JC. A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci. Mol Psychiatry. 2022 Apr;27(4):2264–2272.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

April 2022

Volume

27

Issue

4

Start / End Page

2264 / 2272

Location

England

Related Subject Headings

  • White People
  • Veterans
  • Suicide, Attempted
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Black or African American