Genes that Raise the Risk of Suicide

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Genes that Raise the Risk of Suicide

Jim Windell

           More than 48,000 people took their own lives in this U.S. in 2021 – an increase of about 36% since 2000. The number of people who think about or attempt suicide is even higher. The CDC estimates that some 12 million American adults in 2021 seriously thought about suicide, 3.5 million planned a suicide attempt, and 1.7 million attempted suicide.

           The CDC points out that many factors can increase the risk for suicide; similarly, many factors can protect against the risk for suicide. For instance, people who have experienced violence, including child abuse, bullying, or sexual violence have a higher suicide risk. On the other hand, being connected to family and community support and having easy access to healthcare can decrease suicidal thoughts and behaviors.

           Understanding the risk factors for suicide are very important for clinicians. While the reasons why people attempt suicide are complex, and include external triggers like trauma and stress, they can also include inherited genetic factors. A new study has attempted to better understand the variations in the human genetic code that are associated with risk of attempting suicide.

           Published recently in the American Journal of Psychiatry, the study was conducted by researchers at Huntsman Mental Health Institute at the University of Utah, Icahn School of Medicine at Mount Sinai, Duke University School of Medicine, Durham Veterans Affairs Health Care System, and Vanderbilt University Medical Center. The scientists analyzed data from 22 different populations across the globe, including people of diverse ancestral and ethnic backgrounds.

           According to Anna Docherty, Ph.D., the study’s corresponding author and associate professor of psychiatry at Huntsman Mental Health Institute at the University of Utah, no single gene causes suicide. Rather, the cumulative effect of many different genes influences a person’s risk. “In psychiatry, we have many tiny genetic effects, but when we account for all of them together, we start to see a real genetic risk signal,” Docherty explains.

           In order to tease out such a diffuse signal, researchers applied statistical methods to data collected from the large number of people who were included in the study. This helped them identify genetic variations that are more common among individuals who have attempted suicide. This new analysis combined data from the Million Veteran Program (MVP) and the International Suicide Genetics Consortium (ISGC). Together, these included 43,871 documented suicide attempts and 915,025 ancestry-matched controls, making this the largest genetic study of suicide to date.

           A meta-analysis of the studies identified new genetic variants that correlated with suicide attempt. The researchers then compared all variant signals with previously published genetic data on more than 1,000 other traits and disorders, including psychiatric conditions (e.g., ADHD), physical conditions (e.g., heart disease), and behaviors (e.g., smoking), and determined that genetic variants linked to suicide attempt 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 says. “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.”

           The results show 12 DNA variants, or variations in the human genetic code, that are associated with risk of attempting suicide. The research highlights strong genetic links between suicide attempt and factors that influence physical and behavioral health – including impulsivity, smoking, chronic pain, ADHD, pulmonary conditions, and heart disease. These findings suggest that some of the genetic underpinnings of suicide are shared with these conditions.

           It is hoped that in the future, this information could lead to a better understanding of biological causes of suicide and improvements in prevention strategies. Eventually, such advances could help health care providers identify people who may need mental health support.

           “Many people who die from suicide have significant health conditions associated with that risk,” says Docherty. “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.”

          The scientists involved in this study indicate that they will need to carry out additional studies to determine whether the variants directly or indirectly impact suicide risk – and how. The research so far has shown an association; not cause and effect.

           Understanding how suicide is linked to other health conditions could open doors to new ways of assessing – and treating – suicide risk, Docherty adds. “We want to start to explore the biological underpinnings that are common across suicide and these health factors, because that will lead to the most convincing drug targets.”

           To read the original study, find it with this reference:

Docherty, A. R., Mullins, N., Ashley-Koch, A. E., Qin, X., Coleman, J. R., Shabalin, A., ... & Kelsoe, J. R. (2023). GWAS meta-analysis of suicide attempt: identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors. American Journal of Psychiatry, 180(10), 723-738.


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