Study Links Four Genes with Suicide Risk

Researchers in North Carolina have identified four genes associated with heightened risk of suicidal thoughts and actions. They say the findings could help develop treatments to prevent suicide, the cause of over 700,000 deaths annually and the fourth-leading cause of death among people ages 15 to 29 years old.

“It’s important to note that these genes do not predestine anyone to problems, but it’s also important to understand that there could be heightened risks, particularly when combined with life events,” says Nathan Kimbrel, Ph.D., associate professor in the Department of Psychiatry & Behavioral Sciences at Duke University and co-lead author of the study. 

Conducted by a team from Duke Health and Durham VA, the large, diverse, genome-wide analysis used data from 633,778 U.S. military veterans. Of the participants, 71.4% were of European ancestry; 19.1% African ancestry; 8.1% Hispanic; 1.3% Asian. Study participants were primarily male, with 9% female. Within that group of veterans, 121,211 cases of suicidal thoughts or actions were identified from medical records. Participants were classified as controls if they had no documented lifetime history of self-harm behaviors.

Through a genome-wide analysis of blood samples, the researchers identified numerous genes that were evident among participants with documented cases of suicidal thoughts or actions, regardless of their ancestral background.

Four genes had the strongest links and were previously associated with psychiatric conditions: ESR1, an estrogen receptor previously identified as a causal genetic driver gene of PTSD and depression; DRD2, a dopamine receptor associated with suicide attempts, schizophrenia, mood disorders, ADHD, risky behaviors, and alcohol use disorder; DCC, which is expressed in brain tissue across the lifespan and has been associated with multiple psychiatric conditions and is elevated in the brains of people who die by suicide; and TRAF3, which is associated with antisocial behavior, substance use, and ADHD (lithium, a gold standard treatment for bipolar disorder shown to reduce suicide risk, modulates the expression of TRAF3 and several other inflammatory genes). The researchers also identified nine additional ancestry-specific risk genes.

“While genes account for small amount of risk relative to other factors, we need to better understand the biological pathways that underly a person’s risk for engaging in suicidal behavior,” Kimbrel said.

The study was published recently in the journal JAMA Psychiatry.