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Researchers at the University of Utah Health have identified four genetic changes that occur more frequently among people who die by suicide, which could indicate an increased risk among vulnerable people.
Suicide is the 10th leading cause of death in the United States, causing more than 44,000 deaths each year in the country, a figure similar to the number of deaths caused by the opioid epidemic. Previous studies show that traces of suicide in families are independent of the effects of a shared environment. Researchers at the University of Utah Health are using unique resources in the state to identify the underlying genetic factors that can increase the risk of suicide. The results are available online in the journal Molecular Psychiatry in November.
"Previous studies on families and twins have taught us that there is a significant genetic risk associated with suicide," said Douglas Gray, M.D., professor of psychiatry at U of U Health and senior author of the journal. "Genes are like plans.The first step is to find the genes that increase the risk.The identification of specific genes can lead to new treatments for those who suffer."
With this approach, the team was able to identify variants of four genes (SP110, AGBL2, SUCLA2 and APH1B) that could increase the risk of death by suicide.
"We use large, high-risk families as a magnifying glass to get the good genes that increase the risk of this tragic event," said Hilary Coon, Ph.D., professor of psychiatry at the University of Health d & # 39; U. author on paper.
Focusing on remote parent suicides in 43 high-risk families provides a genetically more homogenous group that magnifies the genetic risks of suicide while minimizing shared environmental effects, such as stresses due to divorce or unemployment, or loneliness. easy access to lethal means. Family genealogical information goes back nine generations.
"In this study, we started by looking for fruits at hand, genomic changes that could affect the structure or function of a gene," said Coon. "We believe these results are just the tip of the iceberg and we will continue to look for other genetic modifications at risk."
The researchers searched for genetic variations in more than 1,300 DNA samples obtained from the Utah Medical Examiner's office from people who died by suicide in that state. These samples represent a subset of a much larger resource with more than 6,000 DNA suicides. The team linked DNA results to the Utah Population database, which contains recent genealogical and medical records of more than eight million people, as well as death certificates dating back to 1904.
The DNA from suicide cases as well as the genealogical structure of the family were de-identified before being communicated to Coon and his team for analysis.
In this study, they identified specific modifications of four genes, but also 207 genes that deserve further analysis to understand their potential role in those who die by suicide. Eighteen of these genes have already been associated with suicide risk. Fifteen of the previously identified genes have also been associated with inflammatory conditions, corroborating the growing evidence of a relationship between inflammation and mental health.
The study has limitations. The majority of suicide cases were of North European origin. All people with a DNA sample in the analysis did not have the data from the medical record to clarify the presence or absence of a mental health diagnosis. Lack of data does not mean lack of diagnosis due to out-of-state care, lack of insurance, cultural factors or stigma.
Coon warns that suicide is like any complex human condition. There may be a variety of genetic changes that make a person more at risk, she said. But many environmental factors will also change this risk.
"It's clear that genetics is only part of the risk for suicide," Coon said. "But we hope these discoveries will lead us to highly susceptible individuals so that we can develop better interventions to help them bypass this risk."
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Todd Darlington, Emily DiBlasi, Ellison Ferris, Alison Fraser, Zhe Yu, William Nancy, Susan Das, Sheila Crowell, Danli Chen, John Anderson, Michael Klein, Leslie Jerominski, Dale Cannon and Andrey Shabalin joined Coon and Gray. Anna Docherty, Megan Williams, Ken Smith, Amanda Bakian and Nicola Camp from the University of Health; Erik Christensen and W. Brandon Callor at the Office of the Medical Examiner of the State of Utah; Brooks Keeshin at Intermountain Healthcare and Qingqin Li Janssen Research & Development LLC Their Work, titled Genome-Scale Significant Regions in 43 High-Risk Families in Utah Involving Multiple Genes Involved in Full Suicide Risk , is published online in the newspaper Molecular Psychiatry.
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