Utah researchers find genetic variants linked to suicide attempts also link to other health conditions

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SALT LAKE CITY — Two University of Utah professors were involved in a study that identifies 12 DNA variants, variations in the human genetic code, linked to the risk of attempting suicide.

In addition to risk of attempting suicide, the research highlighted genetic links between suicide attempts and factors that influence physical and behavioral health — including impulsivity, smoking, chronic pain, ADHD, pulmonary conditions and heart disease.

“One important piece of the puzzle in the evidence that’s been accumulating is the importance of genetic risks in contributing to vulnerability to suicide,” said Hilary Coon, professor in the U.’s Department of Psychiatry and the Huntsman Mental Health Institute, who contributed to the research.

From 2019 to 2021, the age-adjusted suicide rate in Utah was 20.6 per 100,000 people, with an average of 648 suicides per year. Utah had the 9th highest age-adjusted suicide rate in the United States in 2020, according to data from the Utah Department of Health and Human Services.

In 2020, suicide was the leading cause of death for Utahns ages 10-17 and 18-24; it was the second-leading cause of death for ages 25-44 and the fifth-leading cause of death for ages 45-64. Overall, suicide was the eighth-leading cause of death for Utahns, according to the department.

“Many people who die from suicide have significant health conditions associated with that risk,” Anna Docherty, the study’s corresponding author and associate professor of psychiatry at the Huntsman Mental Health Institute, said in a release. “If we can use genetic information to characterize the health risks of those who attempt suicide, we can better identify those patients who need contact with the mental health care system.”

To begin this process, scientists at the Huntsman Mental Health Institute, Icahn School of Medicine at Mount Sinai, Duke University School of Medicine, Durham Veterans Affairs Health Care System and Vanderbilt University Medical Center led a collaboration with multiple institutions worldwide, to analyze data from 22 different populations across the globe.

Our job then is to figure out what those risks sort of are, what that landscape of risk is — and then to mitigate all those exposures to the extent that we can.

–Hilary Coon, U. professor and researcher

“Because suicide is so complex, we need very large samples to begin to really show us the landscape of what’s likely to be many, many, many genes that lead to increased risk,” Coon said. “It’s also the case that risks are likely to differ across worldwide populations, so one of the things that this study starts to get at is to really address that need for diversity in research.”

Researchers applied statistical methods to data collected from a huge sample of people and identified genetic variations that are more common among individuals who have attempted suicide. The analysis combined data from the Million Veteran Program and the International Suicide Genetics Consortium, which included 43,871 documented suicide attempts and 915,025 ancestry-matched controls, making this the largest genetic study of suicide to date.

Coon said she sees the study as a “critical next step” in shedding light on genetic risks and complexities that might lead to suicide risk.

A meta-analysis — a statistical combination of results from two or more separate studies — identified new genetic variants correlated with suicide attempts.

The researchers then compared all variant signals with previously published genetic data on more than 1,000 other traits and disorders, including psychiatric conditions (i.e. ADHD), physical conditions (i.e. heart disease) and behaviors (i.e. smoking), and determined that genetic variants linked to suicide attempts are also linked to other health conditions.

“That allowed us to look at how genetic risk for suicide overlaps with genetic risk for depression, heart disease and many other risk factors,” Docherty said. “It showed significant overlap with mental health conditions, but also a lot of physical health conditions, particularly for smoking and lung-related illnesses. This is something we can’t necessarily see in medical records of people who die from suicide.”

Coon also noted results from the study do not mean people with any one of the noted health factors are at elevated risk for attempting suicide, but combining the genetic predisposition with other stressors — which could include other genetic risk factors, health conditions, life circumstances or traumatic events — could increase that risk.

“Any genetic risk that we discover is not deterministic,” Coon said, using an analogy of obesity to further explain an important takeaway.

“Even if you have the genetic risk for obesity … it’s really mediated by what you eat, by your stress, by your exercise, by all kinds of things that you have control over. It’s a way of, sort of, getting your head around the idea that, yeah, sure, there’s genetic risk out there, but then it can get mediated in so many ways,” Coon said. “Our job then is to figure out what those risks sort of are, what that landscape of risk is — and then to mitigate all those exposures to the extent that we can.”

Essentially, everyone must play the genetic hand they’re dealt, but fate is not sealed by genetics.

While the study was monumental in its scope and findings related to genetic variations associated with the risk of attempting suicide, Coon said that the biggest result from a study like this is its ability to seed new studies and push research closer and closer to clinical translation.

The full study was published Oct. 1 in the American Journal of Psychiatry and can be found here.

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