Suicide

Why Do Mentally Healthy People Die by Suicide?

Does a single gene increase your probability?

Posted Oct 05, 2020

Suicide is common worldwide. Nearly 800,000 people successfully commit suicide every year. In the past, suicide was assumed to be due to some form of mental illness or in reaction to a particular life event. However, people who have no obvious risk factors still die by suicide in significant numbers, making it imperative that we consider the role of another important factor: our genes. Family studies have clearly demonstrated the substantial heritability of suicidal behavior.

The question, then, is what exactly is being inherited? Can genes for depression or other mental illnesses account for the worldwide occurrence? Thus far, finding the culpable gene(s) has not been easy due to the necessity of collecting data from very large numbers of people who have no risk factors.

Two recently published studies collected data from almost 500,000 people with, and without, known mental disorders. Their purpose was to determine whether there was a common genetic variation that might underlie committing suicide. They calculated the genetic correlation between specific gene variations with hundreds of other traits, including those that predispose people to mental disorders, to estimate the genetic contribution to suicide.

The studies confirmed some well-known associations, such as significant genetic correlations between suicide and depressive symptoms, neuroticism, major depressive disorder, and schizophrenia. These results emphasize the heritable component of suicide. The studies also identified two significant genetic correlations with non-psychiatric traits. They confirmed a well-studied positive relationship between genetic risks of suicidal behavior and insomnia.

Second, the authors identified an inverse relationship between the genetic risks of suicide attempt and the mother’s age at first birth. A similar negative correlation between age at first birth and the incidence of schizophrenia has been reported previously. Overall, these findings suggest that the genetic factors that underlie suicide attempt are not distinct from those that underlie schizophrenia.

According to these studies, where does the suicide gene exist on your genome? The most important single nucleotide polymorphism, or SNP, was identified on chromosome 20 in a region of the DNA that does not actually code for any known gene. The gene that lives closest to this region of DNA is 47,000 base-pairs away and is called PREX1. Scientists have speculated that genetic alterations of PREX1 may play a role in the development of depression and autism-like behaviors.

Overall, the results of these very large studies provide support for a genetic transmission of suicide attempt. Future studies may ultimately find a way to predict the risk of attempting suicide in individuals who show no evidence of a mental disorder.

References

Erlangsen G et al (2020) Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study. Molecular Psychiatry, 25:2410–2421 https://doi.org/10.1038/s41380-018-0218-y.

Ruderfer DM (2020) Significant shared heritability underlies suicide attempt and clinically predicted probability of attempting suicide. Molecular Psychiatry (2020) 25:2422–2430 https://doi.org/10.1038/s41380-018-0326-8