In 2020, suicide was the cause of death for 45,979 people in the US alone. It affects men much more than women.
What if suicide has a genetic and hereditary origin?
DNA
A new study published in JAMA Psychiatry has investigated whether there is a genetic basis for suicide, in particular for suicidal thoughts and behavior. This large-scale study, which began in 2011 and is ongoing, included 633,778 US military veterans. The panel included 57,152 women and 576,626 men, 121,118 of African ancestry, 8,285 of Asian ancestry, 452,767 of European ancestry, and 51,608 of Hispanic ancestry. Data from their military medical records were queried: 121,211 people suffered from suicidal thoughts and behaviors, or 19.1%.
What is a GWAS (Genome-Wide Association Study)?
It is thanks to single-nucleotide polymorphisms that we are all different: in height, face, hair color, etc., but also susceptible to developing certain diseases. A GWAS (Genome-Wide Association Study) makes it possible to analyze the SNPs of a large number of people to compare them and determine whether an SNP is correlated with a specific disease, in this case, suicidal thoughts and behavior.
Suicide-prone genes
Analysis of the results showed that over 200 SNPs were associated with suicidal thoughts and behaviors. These 200 SNPs are located in seven different regions (chromosomes 2, 6, 9, 11, 14, 16, and 18). A large proportion involved intronic, i.e., non-coding (genderless) regions. In total, four genes – ESR1, DRD2, TRAF3, and DCC – could be associated with suicidal thoughts and behavior. ESR1 is an estrogen receptor; this gene has already been linked to post-traumatic stress disorder and depression. DRD2 is a dopamine receptor associated with schizophrenia, ADHD, mood disorders, and alcoholism. TRAF3 has been associated with drug addiction and ADHD. Finally, DCC has been associated with psychiatric disorders. These genes are expressed primarily in the brain and pituitary gland.
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Final thoughts
There is now a need to further investigate how these genes affect suicidal thoughts. The next step may be to develop targeted therapies to prevent suicidal risk in genetically susceptible individuals, especially during potentially triggering life events. The authors speculate that lithium, a gold standard treatment for reducing suicide risk, for example, would modulate TRAF3 expression.
References
Kimbrel, N. A., Ashley-Koch, A. E., Qin, X. J., Lindquist, J. H., Garrett, M. E., Dennis, M. F., Hair, L. P., Huffman, J. E., Jacobson, D. A., Madduri, R. K., Trafton, J. A., Coon, H., Docherty, A. R., Mullins, N., Ruderfer, D. M., Harvey, P. D., McMahon, B. H., Oslin, D. W., Beckham, J. C., Hauser, E. R., Hauser, M. A., … (2023). Identification of novel, replicable genetic risk loci for suicidal thoughts and behaviors among US military veterans. JAMA Psychiatry, 80(2), 135–145. https://doi.org/10.1001/jamapsychiatry.2022.3896
