Suicide and Genetics

Duke Health and the Durham NC Veterans Administration release a 2022 report that identified four genes that are linked to an increased risk of suicidal thoughts and behaviors.

The new findings advance the 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 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,” said Nathan Kimbrel, Ph.D., associate professor in the Department of Psychiatry & Behavioral Sciences at Duke and co-lead author of the study publishing.

The study included a large and diverse, genome-wide analysis using 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.

The four genes which had the strongest links, and have been previously associated with psychiatric conditions are:

• ESR1, an estrogen receptor, has been previously identified as a causal genetic driver gene of PTSD and depression, which are risk factors for suicidal behaviors among veterans. Estrogen is also suspected as a cause of sex 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 associated with suicide attempts, schizophrenia, mood disorders, ADHD, risky behaviors, and alcohol use disorder.

• DCC, which is expressed in brain tissue across the lifespan, has been associated with multiple psychiatric conditions 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 shown to reduce suicide risk — modulates the expression of TRAF3 and several other inflammatory genes.