Suicide attempt study confirms genetic basis is not due to underlying psychiatric disorder

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An international consortium of scientists dissects the shared genetic architecture of suicide attempts, psychiatric disorders and non-psychiatric risk factors.

In the largest genetic study of suicide attempts to date, researchers 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 behaviors, depression. sleep disturbances and general poor health. The results of the study, published on November 30, 2021, 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.

Association of common genetic variants of attempted suicide

Level of association of over 7.5 million common genetic variants with a suicide attempt, before and after adjustment for psychiatric disorders. Genetic variants above the gray line pass the level of statistical significance. Credit: Niamh Mullins, PhD, Assistant Professor of Psychiatry, Icahn School of Medicine at Mount Sinai

“In addition to identifying the location of risk for 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 overlaps with the genetics of smoking, pain, risk taking, sleep disturbances and general poor health, ”said Niamh Mullins, PhD, assistant professor of psychiatric genomics at Icahn School of Medicine at Mount Sinai, co-founder and co-chair of the consortium and main author of the paper. “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. comorbid psychiatric illness, but may instead be the result of shared biology with non-psychiatric risk factors.

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 attempts 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 comprises 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.

If you are in crisis, please call the National Suicide Prevention 24 Hour Lifeline at 1-800-273-TALK (8255), or contact Crisis Text Line by sending TALK to 741741, or visit their website at: http: // suicidepreventionlifeline.org.

Reference: “Dissecting the Shared Genetic Architecture of Suicide Attempts, Psychiatric Disorders and Known Risk Factors” by Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan RI Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F . Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke , Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández- Aranda, Manfred M Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-C heng Liao, Klaus Lieb, Lis a Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton HD Bau, Bernhard T. Baune , Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Fr anziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner… Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis , J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour and Douglas M. Ruderfer, September 9, 2021, Biological Psychiatry.
DOI: 10.1016 / j.biopsych.2021.05.029


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