Researchers dissect the shared genetic architecture of suicide attempts and psychiatric disorders

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In the largest genetic study of suicide attempts to date, researchers have identified a region of the genome on chromosome 7 containing DNA variations that increase a person’s risk of attempting suicide.

The study also found an overlap in the genetic basis of suicide attempts and that of related psychiatric disorders, particularly major depression, and also with that of non-psychiatric risk factors such as smoking, risky behavior, depression. sleep disturbances and poor general health. The results of the study, published on November 30 in Biological Psychiatry, suggest that the genetic foundations of suicide attempts are partially shared and partially distinct from those of associated psychiatric disorders.

Suicide is a global public health problem, responsible for nearly 800,000 deaths per year. Non-fatal suicide attempts are estimated to occur more than 20 times for every suicide death and are a major source of disability, reduced quality of life, and social and economic burden. Suicidal thoughts and behaviors can be reduced with appropriate mental health support and treatment. Therefore, it is essential to better understand the underlying biological pathways involved in suicide attempts or suicidal thoughts, which could provide potential avenues for treatment and prevention strategies.

To help elucidate the underlying biology of suicide attempts, an international consortium of scientists from the International Suicide Genetics Consortium conducted a genome-wide association study. This method involves scanning the DNA of many people, looking for genetic markers that were more common in those who had attempted suicide. The team scanned more than 7.5 million common variations in the DNA sequence of nearly 550,000 people, of which nearly 30,000 had attempted suicide.

In addition to identifying the location of the risk of suicide attempt on chromosome 7, we found a strong overlap in the genetic basis of suicide attempt and that of psychiatric disorders, particularly major depression, as well as some overlap. with the genetics of smoking, pain, risk-taking, sleep disturbances and general poor health. This genetic overlap with non-psychiatric risk factors remained largely unchanged after adjusting for psychiatric disorders, suggesting that a substantial component of the biological basis of the suicide attempt is not simply a by-product of ‘comorbid psychiatric illness, but may instead be the result of a shared biology. with non-psychiatric risk factors. “

Niamh Mullins, PhD, Assistant Professor of Psychiatric Genomics at Icahn School of Medicine, Mount Sinai Health System

Mullins is also a co-founder and co-chair of the consortium, and lead author of the article.

The association between genetic variations on chromosome 7 and the risk of attempted suicide was also not mediated by comorbid psychiatric disorders, and was replicated through an independent analysis of more than 14,000 veterans who had done so. a suicide attempt from the Million Veterans Program, a national research program to learn how genes, lifestyle and military exposures affect health and disease.

“This study is an exciting advance in our understanding of the relationship between the genetics of suicide attempt and that of psychiatric and non-psychiatric risk factors,” said JooEun Kang, MD-PhD student at Vanderbilt University Medical Center and co. – main author of this paper.

DNA variations in this region have previously been linked to insomnia, smoking, and risky behaviors, and while future work is needed to uncover the underlying biological mechanism, findings like these bring closer researchers understanding the neurobiology of suicidality.

“The study results also underscore the importance of investigating potential direct causal pathways between these risk factors and suicide attempt in patients with and without psychiatric illness,” added Douglas Ruderfer, PhD, associate professor of genetic medicine, psychiatry and biomedical informatics at Vanderbilt. University Medical Center, co-founder and co-chair of the consortium, and lead author of the article.

The International Suicide Genetics Consortium includes more than 260 scientists in more than 20 countries dedicated to studying the genetic basis of suicidality. Their work forms the basis for future, larger studies to identify genetic risk factors for suicide attempts in other areas of the genome, as well as additional studies focusing on suicidal thoughts. The ultimate goal of this research is to better understand the underlying biological pathways involved in suicidality, offering potential avenues for treatment and prevention strategies.

Source:

Mount Sinai Health System

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