They identify 4 genes associated with suicidal thoughts and behaviors

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They identify four genes –ESR1, DRD2, DCC, TRAF3– that appear regularly in people with a history of suicidal thoughts or behaviors and may help to understand how genetic inheritance influences these disorders.

They identify 4 genes associated with suicidal thoughts and behaviors

The COVID-19 pandemic has influenced the mental health and emotional well-being of the population, to the point that suicide rates have increased significantly in Spain during 2020 and 2021. In 2020, the first year of the pandemic, the life 3,941 people, a figure that rose to 4,003 in 2021, according to data from the National Institute of Statistics (INE). Having a mental disorder and environmental or personal factors can increase the risk of suicide, but the appearance of suicidal thoughts and behaviors could also be related to a genetic predisposition.

This is at least the conclusion reached by a new study led by researchers from the Duke University Medical Center and Durham VA, in North Carolina (USA), which has identified four genes that appear regularly among people in whom cases of suicidal thoughts or behavior have been documented after analyzing their entire genome. The results have been published in JAMA Psychiatry.

Nathan Kimbrel, from the Department of Psychiatry and Behavioral Sciences at Duke University and co-senior author of the study, pointed out that, although it is important to note that these genes do not predestine anyone to present these alterations, they do “might confer a greater risk, particularly when combined with life events.

“The findings advance our understanding of how inherited risk factors play a role in the pathology of suicidal thoughts and actions.”

“While more data is needed to determine whether identification of genetic markers could lead to targeted treatments, it is clear that the findings advance our understanding of how inherited risk factors play a role in the pathology of suicidal thoughts and actions. ”, they point out in the article.

Genes that may increase the risk of suicide

Krimbel’s team conducted an extensive and diverse genome-wide analysis using data from 633,778 US military veterans, of whom 71.4% were of European descent; 19.1% of African descent; 8.1% Hispanic and 1.3% Asian. Only 9% were women. Among all participants and from their medical records, 121,211 cases of suicidal thoughts or actions were detected from medical records. Those individuals who did not have a documented history of self-injurious behaviors were classified as a control group.

Using genome-wide analysis of blood samples, the researchers identified numerous genes that were evident among participants with documented cases of suicidal thoughts or actions. Specifically, they identified 7 significant genome-wide cross-ancestry risk loci (physical location of a specific gene on a chromosome) through a meta-analysis. The main loci were replicated independently in a large international cohort.

They found four genes that have previously been linked to psychiatric disorders and had the strongest links to suicidal ideation and behavior: ESR1, an estrogen receptor, was previously identified as a causative gene drive for post-traumatic stress disorder (PTSD). ) and depression, which are risk factors for suicidal behavior among veterans. “Estrogen is also suspected to be the cause of sex differences in rates of depression, and loss of ESR1 has been found to produce effects in brain tissue in men,” Krimbel explained.

Another gene is DRD2, a dopamine receptor that has been linked to suicide attempts, schizophrenia, mood disorders, attention deficit hyperactivity disorder (ADHD), risk behaviors, and alcohol use disorder. The third gene identified is DCC, which is expressed in brain tissue throughout life, has been linked to numerous psychiatric problems, and is elevated in the brains of people who commit suicide.

TRAF3, the last of which is related to antisocial behavior, substance use and ADHD. Lithium, the treatment of choice for bipolar disorder that has been shown to reduce the risk of suicide, modulates the expression of TRAF3 and other inflammatory genes. In addition to those genes, the study authors also identified nine additional ancestry-specific risk genes.

These genes, Kimbrel notes, constitute a small amount of risk relative to other factors, but, he says, “we need to better understand the biological pathways that underlie a person’s risk of engaging in suicidal behavior.” The researcher stresses that suicide is the fourth leading cause of death among young people between the ages of 15 and 29 and each year more than 700,000 people take their lives. “So the more we know, the better we can prevent these tragic deaths.”

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