Scientists ID Genetic Risk Factors For Suicide

By  |  October 28, 2021, 3:17 PM  |  Techonomy Exclusive

Suicide is a global epidemic, taking nearly 800,000 lives each year. And in the U.S., where suicide rates rose by 33 percent between 1999 and 2019, getting support and resources to the right people at the right time is a pressing need.

The problem is so critical that large groups of scientists around the world have banded together to study it. Recently, they mined genomic data from nearly a million people and identified specific genetic variants that appear to be associated with increased risk of suicide. Those discoveries could have important implications for getting useful medications to at-risk individuals, or for predictive diagnostic tools that would flag people who might need help.

Suicide is an incredibly complex phenomenon, and scientists don’t believe that genetic risk factors tell the whole story. Accurate prediction of which people would attempt suicide in a particular situation would require a sophisticated understanding of genetic, environmental, psychological, sociological, and other factors.

Still, the new genetic findings could be a major step forward. Results from in-depth analyses of attempted suicides in two large populations — including nearly 30,000 people tracked by the International Suicide Genetics Consortium and more than 14,000 in the Million Veteran Program, plus more than 900,000 people who had not attempted suicide as controls — were presented this month at the annual meeting of the American Society of Human Genetics. By comparing genetic differences between people who had made suicide attempts and those who hadn’t, scientists were able to create a list of DNA variants found only in individuals with recorded suicide attempts. Because veterans attempt suicide more often than civilians, including their data was key to these discoveries.

The scientists looked at which variants occurred most often among people who had attempted suicide, and investigated their biological function. Many were associated with traits known to be linked to suicide risk, such as oxytocin signaling, which is important for social bonding, or circadian rhythm, which could explain the higher sleep dysfunction reported in people who attempt suicide.

A particularly revealing sign to the scientists was that many of the findings dovetailed between the veteran and the civilian populations studied. “We’ve seen the same results in two large data sets,” says Elizabeth Hauser, a professor and biostatistician at Duke University who helped crunch the numbers. “That really gives us confidence [in these results].”

The genetic data offer some hopeful possibilities. By highlighting certain biological pathways that may be associated with suicide risk, the data could lead to new clinical treatments. Currently approved drugs that work on those same pathways might be repurposed for use in at-risk patients, and in the longer term, drug developers could create new treatments based on specific genetic variants.

In addition, further validation of the genetic variants could pave the way for a diagnostic test that would help to identify people who are at increased risk for attempting suicide — understanding, of course, that genetics is just one piece of the puzzle. “Just because you might have a particular genetic risk factor, that doesn’t necessarily mean that you will in fact go on to develop these suicidal behaviors,” says Allison Ashley-Koch, a professor and genetic epidemiologist at Duke who participated in these studies. “It just means you may benefit from some additional targeted interventions to help prevent it.”

Nate Kimbrel, a clinical psychologist at Duke and the Durham VA Medical Center who helped lead these studies, hopes that genetic data will ultimately be incorporated alongside more traditional risk factors to hone predictions of which people are most at risk. He and his colleagues previously established the Durham Risk Score, a checklist that helps clinicians identify chronic risk factors to understand a patient’s likelihood of attempting suicide. When high-risk people face acute stressors, such as a romantic breakup or sudden financial hardship, their clinician can offer more intensive support than might be needed for someone at low risk of suicide. If genetic data could be used to pinpoint a person’s risk with greater accuracy, it could give psychologists and psychiatrists a better opportunity to tailor interventions for each patient.

Of course, the possibility of using genetic data for this purpose raises concerns about privacy and each person’s willingness to get tested. “I would view it as something that people would always need to have control over,” Kimbrel says. “People need to be able to make that decision. I would see it being part of a conversation with your provider.”

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