Four genes associated with an increased risk of suicidal thoughts and behaviors

Researchers at Duke Health and the Durham Veterans Administration conducted a large study of military personnel to identify four genes
associated with an increased risk of suicidal thoughts and behaviors.

While more work is needed to determine whether identification of genetic markers could lead to targeted therapies, the findings advance an understanding
of how genetic risk factors play a role in the pathology of suicidal thoughts and behaviors.

Dr.
Nathan Kimbrel, an associate professor in Duke's Department of Psychiatry and Behavioral Sciences, said, "It's important to note that these genes are not doomed to problems for anyone, but it's also important to understand that risk can increase, especially when
combined with life events.
" He is the co-lead author of the study, which was published online Dec.
14 in
the Journal of American Medical Association Psychiatry.

Kimbrel and his colleagues, including co-first author Allison Ashley-Koch, a professor of medicine at Duke University, conducted a large, diverse, genome-wide analysis
using data from 633,778 U.
S.
veterans.
Of the participants, 71.
4% were of European ancestry; 19.
1% of African ancestry; 8.
1% Hispanic; 1.
3%
in Asia.
The study participants were predominantly male and 9% were female
.

Among this group of veterans, 121211 cases of suicidal thoughts or behaviors
were identified from medical records.
If participants did not have a documented history of self-injurious behavior, they were classified as a control group
.

Through genome-wide analysis of blood samples, the researchers found a number of distinct genes in participants with recorded suicidal thoughts or behaviors, regardless of their ancestral background
.
There are four genes most strongly associated with mental illness, and they have all previously been linked to mental illness:

• ESR1, an estrogen receptor, has previously been identified as a causal genetic driver of PTSD and depression, a risk factor
  for suicidal behavior in veterans.
  Estrogen is also suspected to be responsible for the gender difference in the incidence of depression, and ESR1 deficiency has been found to have an effect
  on brain tissue in men.
  

• DRD2 is a dopamine receptor associated with suicide attempts, schizophrenia, mood disorders, attention deficit hyperactivity disorder, risky behaviors, and alcohol use disorder
  .
  

• DCC is expressed in brain tissue throughout a person's life, and it has been linked to a variety of psychiatric disorders, with elevated levels of DCC in the brains of people who have died by suicide
  .
  

• TRAF3 is associated
  with antisocial behavior, substance use, and ADHD.
  Lithium, the gold standard treatment for bipolar disorder, has been shown to reduce suicide risk, and it regulates the expression
  of TRAF3 and several other inflammatory genes.
  

In addition to these genes, the researchers identified 9 additional ancestor-specific risk genes
.

"While genes account for only a small risk relative to other factors, we need to better understand the biological pathways
that lead to a person's risk of suicidal behavior," Kimbrel said.
Suicide kills more than 700,000 people each year and is the fourth leading
cause of death among people aged 15 to 29.
The more we know, the better we can prevent these tragic deaths
.
”

This study was supported
by the Veterans Health Administration's Division of Clinical Research and Development Services (I01CX001729, lK6BX003777), the U.
S.
Department of Veterans Affairs, and the U.
S.
Department of Energy.
Supporters of all research are listed
in the publication.