Study finds four genes linked to increased risk of suicidal thoughts and behaviors

A large study of military personnel by researchers at Duke Health and Durham VA identified four genes linked to an increased risk of suicidal thoughts and behaviors.

While further work is needed to determine whether identifying genetic markers could lead to targeted treatments, the findings advance understanding of how inherited risk factors play a role in the pathology of suicidal thoughts and actions. .

“It’s important to note that these genes don’t predestine anyone for trouble, but it’s also important to understand that there could be increased risks, especially when combined with life events,” Nathan said. Kimbrel, Ph.D., associate professor in the Dept. of Psychiatry & Behavioral Sciences at Duke and co-lead author of the study published online December 14 in the journal JAMA Psychiatry.

Kimbrel and his colleagues, including co-lead author Allison Ashley-Koch, a professor in the Duke Department of Medicine, conducted a large, diverse, genome-wide analysis using data from 633,778 U.S. military veterans. Of the participants, 71.4% were of European descent; 19.1% of African descent; 8.1% Hispanic; 1.3% Asian. Study participants were predominantly male, with 9% female.

Within this group of veterans, 121,211 instances of suicidal thoughts or actions were identified from medical records. Participants were classified as controls if they had no documented history of self-injurious behaviors.

Through genome-wide analysis of blood samples, the researchers identified many genes that were evident in participants with documented cases of suicidal thoughts or actions, regardless of their ancestral background. Four genes had the strongest links and have been previously linked to psychiatric disorders:

  • ESR1, an estrogen receptor, has previously been identified as a genetic causative gene responsible for PTSD and depression, which are risk factors for suicidal behaviors in veterans. Estrogen is also suspected to drive gender differences in depression rates, and loss of ESR1 has been found to produce effects on brain tissue in men.
  • DRD2, a dopamine receptor, has been linked to suicide attempts, schizophrenia, mood disorders, ADHD, risky behaviors and alcohol use disorders.
  • DCC, which is expressed in brain tissue throughout life, has been linked to multiple psychiatric disorders and is elevated in the brains of people who die by suicide.
  • TRAF3 is associated with antisocial behavior, substance use, and ADHD. Lithium – a gold standard treatment for bipolar disorder that reduces suicide risk – modulates the expression of TRAF3 and several other inflammatory genes.

In addition to these genes, the researchers also identified nine other ancestry-specific risk genes.

While genes represent a small amount of risk compared to other factors, we need to better understand the biological pathways that underlie a person’s risk for suicidal behavior. Suicide is the cause of more than 700,000 deaths per year and is the fourth leading cause of death among people aged 15-29. The more we know, the better we can prevent these tragic deaths.”

Nathan Kimbrel, Ph.D., Associate Professor, Department of Psychiatry and Behavioral Sciences, Duke University

Besides Kimbrel and Ashley-Koch, study authors include Xue J. Qin, Jennifer H. Lindquist, Melanie E. Garrett, Michelle F. Dennis, Lauren P. Hair, Jennifer E. Huffman, Daniel A. Jacobson, Ravi K. Madduri, Jodie A. Trafton, Hilary Coon, Anna R. Docherty, Niamh Mullins, Douglas M. Ruderfer, Philip D. Harvey, Benjamin H. McMahon, David W. Oslin, Jean C. Beckham, Elizabeth R. Hauser, Michael A Hauser, the MVP Suicide Exemplar Workgroup, the International Suicide Genetics Consortium, the VA Mid-Atlantic MIRECC Workgroup, and the VA Million Veteran Program.

This research was supported by the Clinical Science Research and Development Service of the Veterans Health Administration (I01CX001729, lK6BX003777), the US Department of Veterans Affairs, and the US Department of Energy. All of the study’s supporters are listed in the publication.

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