Researchers identify gene expression signatures linked to suicide risk

Is the risk of suicide in our genes?

Findings from an international scientific team led by the Translational Genomics Research Institute (TGen), a subsidiary of City of Hope, suggest that gene expression studies may offer insight into the underlying causes of suicide, a problem of very complex public health that kills more than 800,000 people each year worldwide.

Examination of brain tissue samples from 380 individuals -; 141 people died by suicide and 239 died from other causes -; revealed five genes that affect multiple regions of the brain. The results of the study suggest that these genes may be beneficial in helping to prevent suicide. The results appear in the newspaper European neuropsychopharmacology.

If independent replication studies validate our results, they may be able to inform predictive models of suicide risk in patients with mental disorders. “

Ignazio Piras, Ph.D., Research Assistant Professor in the Division of Neurogenomics at TGen and lead author of the study

“Our results support the involvement in suicidal behavior of astrocytes and microglia (cells of the brain and central nervous system), the stress response and the immune system,” said Dr. Piras.

Using Gene Expression Omnibus, a genomic data repository maintained by the National Institutes of Health, researchers focused on three regions of the brain:

  • The orbitofrontal cortex, which is involved in sensory detection, emotions and memory;
  • The prefrontal cortex, which is associated with the planning of complex cognitive behavior, personality expression, decision making, and moderation of social behavior;
  • Dorsolateral prefrontal cortex, which is concerned with how to interact with stimuli.

A serious public health problem

Suicides contribute 15% of all injury deaths worldwide, a figure that is probably underestimated, according to previous studies. Predicting risks and implementing effective prevention models are among the main goals of suicide research. Previous models, based on clinical and behavioral evaluations, have shown “extremely low” predictive validity.

In this study, the researchers attempted to increase the predictive nature of the risk models by integrating biological information from different studies conducted on a wide range of regions of the brain. Previous studies have also shown statistically significant genomic associations in patients with mood disorders.

“Stratifying patients according to validated gene expression signatures will help assess risk for suicidal behavior in the future,” said Mirko Manchia, MD, Ph.D., assistant professor of psychiatry at the University of Cagliari ( Italy) and one of the study researchers. main authors.

The researchers found reduced expression of five key genes -; KCNJ2, AGT, PMP2, VEZF1 and A2M -; in samples from individuals who died by suicide, all potentially linked to relevant alterations in molecular and cellular mechanisms. For example, previous studies have linked A2M to Alzheimer’s disease and neurocognitive decline.

These molecular targets have the potential for follow-up analysis and implementation in risk prediction models.

“We will plan follow-up studies, including additional data sources and integrative genomic analysis approaches, to validate candidate targets,” said Clement Zai, Ph.D., assistant professor at the University of Toronto and another of the study’s lead authors.

International team of collaborators

The University of Ottawa (Canada), the University of Barcelona (Spain), Dalhousie University (Canada), the Center for Addiction and Mental Health (Canada) and the Broad Institute (MIT / Harvard) also contributed to this study.

Study support -; A review and meta-analysis of gene expression profiles in suicide -; were from the University of Cagliari, the Spanish Ministry of Science and Innovation, the CAMH Foundation, the Foundation for Brain and Behavior Research and a Sylvia B Early Career Research Fellowship Chase.


Journal reference:

Piras, IS, et al. (2021) A review and meta-analysis of gene expression profiles in suicide. European neuropsychopharmacology.

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