In the largest genetic study of suicide attempt to date, researchers have identified a region of the genome containing variants that increase an individual’s risk.
Suicide is an ongoing worldwide public health problem. It accounts for almost 800,000 deaths per year. Nonfatal suicide attempts occur over 20 times more frequently and are a major source of disability, reduce quality of life, and social and economic burden. The lifetime prevalence in adults ranges from 0.5-5%. In addition, there are several well-known comorbidities and risk factors for suicide attempt. Psychiatric illnesses have the strongest impact on suicide rates. Although, the vast majority of patients with such illnesses do not attempt suicide.
Estimates from genetic epidemiology studies have indicated that the heritability of suicide and suicide attempt ranges from 17-55%. Other studies have also highlighted shared genetic aetiology between suicide attempt and psychiatric disorders. Major depressive disorder (MDD) has shown the largest overlap. Most importantly, studies have demonstrated a genetic component of suicide attempt that is partially distinct from psychiatric disorders.
GWAS of suicide attempt
A recent study, published in Biological Psychiatry, has presented the first GWAS meta-analysis of suicide attempt from the International Suicide Genetics Consortium (ISGC). This specifically included 29,000 suicide attempt or suicide cases and 519,961 controls from 18 cohorts worldwide. The team investigated the shared and divergent genetic architectures of suicide attempt, psychiatric disorders and other known risk factors.
The researchers identified two loci that reached genome-wide significance for suicide attempt. These loci were in the region of the major histocompatibility complex and an intergenic locus on chromosome 7. The latter remained associated with suicide attempt even after adjusting for psychiatric disorders. This finding was also replicated in an independent cohort of more than 14,00 veterans, from the Million Veterans Program, who had made a suicide attempt.
In addition to identifying the loci on chromosome 7, the team also uncovered a strong overlap in the genetic basis of suicide attempt and that of psychiatric disorders, particularly MDD, as well as some overlap with the genetics of smoking, pain, risk-taking, sleep disturbances and poorer general health.
Niamh Mullins, lead author, explained:
“This genetic overlap with non-psychiatric risk factors was largely unchanged by adjusting for psychiatric disorders, which suggests that a substantial component of the biological basis of suicide attempt is not simply a by-product of comorbid psychiatric disease, but instead may be the result of shared biology with non-psychiatric risk factors.”
Overall, these findings reveal a risk locus that contributes more strongly to suicide attempt than other phenotypes. It also suggests a shared underlying biology between suicide attempt and known nonpsychiatric risk factors. This highlights the importance of studying the potential causal pathways between these risk factors and suicide attempt in patients with and without psychiatric illnesses.
Image credit: canva