New research finds four genetic variants that may raise the risk of dying by suicide, regardless of environmental factors. The study also identifies hundreds of other genes that require further analysis and that may also raise the likelihood that a person dies by suicide.

According to the World Health Organization (WHO), almost 800,000 people die by suicide every year.

Among people aged 15–29, suicide is the second leading cause of death worldwide.

In the US, almost 45,000 people die as a result of suicide every year, making suicide the 10th leading cause of death among individuals of all ages.

Men who are white and middle-aged, however, are at the highest risk of dying by suicide.

Although the environment has an effect on the incidence of suicide, some studies have pointed out that genetic factors also play a key role. In fact, older studies have estimated the heritability of suicide at 50%.

New research that appears in the journal Molecular Psychiatry uses modern genomic sequencing techniques to find specific genetic factors that may raise the risk of suicide.

Dr. Douglas Gray, who is a professor of psychiatry at the University of Utah (U of U) Health in Salt Lake City, is the senior author on the paper.

He explains the motivation for the study, saying, "Past studies of families and twins informed us that there is significant genetic risk associated with suicide."

"Genes are like blueprints. The first step is to find the genes that increase risk. Identifying specific genes may lead to new treatments for those who [need them]," says Dr. Gray.

4 genetic variants and 207 genes found

To identify these genes, Dr. Gray and colleagues zoomed in on 43 families that were at a higher risk of suicide.

By focusing on such a "genetically homogeneous group," the researchers reduced the influence of environmental factors—such as stress due to a divorce, unemployment, or the loss of a loved one, or having easy access to means of taking one's life, such as firearms.

Hilary Coon, PhD—a professor of psychiatry at U of U Health and the first author of the paper—explains the methods used in the research. "In this study," she says, "we began by looking for the low-hanging fruit, the genomic changes that could affect the structure or function of a gene."

The researchers examined the cases of suicide among the very distant relatives of the 43 families. "We are using high-risk very extended families like a magnifying glass to get us to the right genes that increase the risk for this [...] outcome," Prof. Coon goes on.

Overall, Dr. Gray and team examined genetic variants in over 1,300 DNA samples from people who died by suicide in Utah. The researchers correlated the DNA results with the Utah Population database, which has genealogical data and the medical records of over 8 million people.

The analysis revealed specific variations in four genes that may raise the risk of suicide-related death: SP110, AGBL2, SUCLA2, and APH1B.

Also, the researchers identified an additional 207 genes that may prove to be key in influencing suicide risk and that need further analysis.

Previous studies have linked 18 of these genes with suicide risk and 15 of them with inflammation, further strengthening the hypothesis that inflammation and mental health are connected.

All in all, "the current work has produced several important lines of evidence," explain the authors.

Strengths and limitations of the study

Despite the significant findings, the authors point out some limitations to their study. For instance, most cases of suicide were from people of Northern European ancestry, which limits the results.

Also, the researchers did not have access to the mental health history of each and every person. Potential diagnoses of mental health issues that the researchers were not aware of may have influenced the results.

As with any complex human condition, cautions Prof. Coon, many environmental factors can still modify the genetic risk.

"Clearly genetics is only one part of [the] risk when it comes to suicide [...] But we are hoping these discoveries will lead us to highly susceptible individuals so we can develop better interventions to help them circumvent this risk."

—Prof. Hilary Coon, PhD

"We think these results are just the tip of the iceberg. We will continue to search for additional gene changes that lead to risk," Prof. Coon concludes.