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

Journal Article · · Molecular Psychiatry
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3];  [4];  [5];  [6];  [6]; ORCiD logo [7]; ORCiD logo [8]; ORCiD logo [9];  [10];  [11];  [12]; ORCiD logo [13]; ORCiD logo [14]; ORCiD logo [13];  [15];  [16];  [17];  [3] more »;  [2];  [18] « less
  1. Durham Veterans Affairs (VA) Health Care System, Durham, NC (United States); VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC (United States); VA Health Services Research and Development Center of Innovation to Accelerate Discovery and Practice Transformation, Durham, NC (United States); Duke Univ., Durham, NC (United States)
  2. Duke Molecular Physiology Institute, Durham, NC (United States); Duke Univ., Durham, NC (United States)
  3. Durham Veterans Affairs (VA) Health Care System, Durham, NC (United States); Duke Molecular Physiology Institute, Durham, NC (United States)
  4. VA Health Services Research and Development Center of Innovation to Accelerate Discovery and Practice Transformation, Durham, NC (United States)
  5. Duke Molecular Physiology Institute, Durham, NC (United States)
  6. Durham Veterans Affairs (VA) Health Care System, Durham, NC (United States); Duke Univ. School of Medicine, Durham, NC (United States)
  7. VA Boston Healthcare System, MA (United States)
  8. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
  9. Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
  10. VA Palo Alto Health Care System, Menlo Park, CA (United States)
  11. Univ. of Utah School of Medicine, Salt Lake City, UT (United States)
  12. Univ. of Utah School of Medicine, Salt Lake City, UT (United States); Virginia Commonwealth Univ., Richmond, VA (United States)
  13. Vanderbilt Univ. Medical Center, Nashville, TN (United States)
  14. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
  15. University of Miami Miller School of Medicine, Miami, FL (United States); Bruce W. Carter VA Medical Center, Miami, FL (United States)
  16. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  17. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA (United States); Univ. of Pennsylvania, Philadelphia, PA (United States)
  18. Durham Veterans Affairs (VA) Health Care System, Durham, NC (United States); VA Mid-Atlantic Mental Illness Research, Education and Clinical Center, Durham, NC (United States); Duke University School of Medicine, Durham, NC (United States)
+ Show Author Affiliations

In this study, 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.

Research Organization:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
Veterans Health Administration (VHA) Office of Research and Development (ORD); USDOE Office of Science (SC), Basic Energy Sciences (BES); US Department of Veterans Affairs
Contributing Organization:
VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; International Suicide Genetics Consortium
Grant/Contract Number:
AC05-00OR22725; I01CX001729; lK6BX003777; AC02-06CH11357
OSTI ID:
1876345
Alternate ID(s):
OSTI ID: 1959967
Journal Information:
Molecular Psychiatry, Vol. 27, Issue 4; ISSN 1359-4184
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

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