Health Science Reviews

By Rio Harrison

The issue

Suicide remains a global public health challenge that accounts for more than 700 000 deaths annually worldwide. Although public health frameworks focus heavily on psychosocial intervention, understanding the biological mechanisms resulting in suicidal behaviour is a massive unmet clinical need and remains a complex puzzle in science.

To deal with this challenge, an international team of researchers, made up of the International Suicide Genetics Consortium (ISGC) and the VA Million Veteran Program (MVP)conducted one of the largest genome-wide association studies (GWAS) of suicide attempts to date.

The question

Whether analysing the genetic makeup/ DNA of almost one million people can uncover certain genes associated with suicidal behaviour and how this risk for suicide links to other physical and mental health conditions such as ADHD, depression, and chronic pain.

How it was performed

The scientists involved in this study integrated genetic and clinical data from 22 cohorts, making up a total of 43,871 individuals who have a recorded history of suicide attempts, as well as 915,025 ancestry-matched controls. (Controls whose genetic background resembles that of the cases in the study).

Through looking at a large number (millions) of single-nucleotide polymorphisms (SNPs) across different ancestral backgrounds, including African, European, Hispanic, and East Asian populations, as well as blended ancestry (admixtures). A meta-analysis was conducted to identify and map shared genetic markers (SNP’s) for suicide risk. Following this, these variants were subjected to a pathway enrichment experiment to identify the biological pathways and drug targets corresponding to the genes where these variants were mapped.

What they found

They managed to find 12 genome-wide significant loci linked to suicide attempts. Some of the genes where these variants are located include SLC6A9, NLGN1, SOX5, PDE4B, CACNG2, and DRD2, which is a significant dopamine receptor in reward perception and mood regulation.

Risk variants were heavily expressed in the brain tissue and pituitary glands, which aligns with the fact that genes implicated in the serotonergic and dopaminergic system of the brain have long been linked to suicidal behaviour.

It was also revealed through gene set enrichment that there was a significant overlap with targets of antidepressants and antipsychotics, which allowed the researchers to confirm that these medications target the actual brain systems involved in suicidal behaviour and mental health. It was also found that there was a statistically significant correlation between suicide attempts and smoking, ADHD, and chronic pain.

Takeaway

Suicide is extremely complex and is influenced by many environmental, social, psychosocial, and genetic factors that involve interactions between many genes. It is also shown that suicide is not only caused by psychiatric conditions such as depression and schizophrenia. Instead, we see that it shares genetic links and markers with chronic pain and impulse control, creating a broader “stress-diathesis” model where physical health impacts and how we handle stress combine to influence suicide risk.

While genetic testing can’t simply predict a person’s risk for suicide yet. Studies using larger cohorts and diverse populations bring us closer to personalized treatment and targeted therapy in which drug selection and dosage can be tailored to an individual’s genetic makeup and risk variants, improving treatment efficacy and decreasing the risk for adverse drug reactions and suicide simultaneously.

Reference

Docherty, A.R. et al. (1970) Gwas meta-analysis of suicide attempt: Identification of 12 genome-wide significant loci and implication of genetic risks for specific health factors, DigitalCommons@TMC.Available at: https://digitalcommons.library.tmc.edu/uthmed_docs/2633/  (Accessed: 03 August 2026).