Four genes showed strong associations with increased risk of
suicidal thoughts and behaviors in US military veterans regardless of ancestral background: ESR1, DRD2, TRAF3, and DCC. Researchers published the findings online ahead of print in
JAMA Psychiatry.
“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 co-lead author Nathan Kimbrel, PhD, associate professor in the department of psychiatry and behavioral sciences at Duke University Medical Center in Durham, North Carolina.
The genes were identified through a genome-wide analysis of data from 633,778 veterans. Among participants, 71.4% were of European ancestry, 19.1% of African ancestry, 8.1% Hispanic, and 1.3% were Asian. Of the participants, 9% were women.
Some 19.1% of participants, or 121,211 of the veterans, had documented suicidal thoughts or behaviors. The remainder of the participants were classified as controls.
According to researchers, the genes with the strongest associations with suicidal thoughts or behaviors were:
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ESR1, an estrogen receptor, which has been previously identified as a causal genetic driver gene of posttraumatic stress disorder and depression;
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DRD2, a dopamine receptor, which has been associated with suicide attempts, schizophrenia, mood disorders, attention-deficit/hyperactivity disorder (ADHD), risky behaviors, and alcohol use disorder;
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DCC, a gene expressed in brain tissue, which has been associated with multiple psychiatric conditions and is elevated in the brains of people who die by suicide; and
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TRAF3, a gene associated with antisocial behavior, substance use, and ADHD. Lithium, which has been shown to reduce suicide risk in patients with bipolar disorder, modulates the expression of TRAF3 and several other inflammatory genes, the research team explained.
The study also identified nine ancestry-specific genes that were associated with increased risk for suicidal thoughts and behaviors in participants.
“More work is needed to replicate these findings,” researchers wrote, “and to determine if and how these genes might impact clinical care.”