Genetics of Suicide

Genes (Basel). 2025 Apr 3;16(4):428. doi: 10.3390/genes16040428.

ABSTRACT

Over the past two decades, suicide has consistently ranked among the leading causes of death in the United States. While suicide deaths are closely associated with uicidal ideation and attempts, these are not good predictors of future suicide deaths. Establishing who is at risk of suicide remains a challenge that is mostly hampered by the lack of understanding of its pathophysiology. Nonetheless, evidence continues to accumulate suggesting that suicide is driven by a complex and dynamic interaction between environmental factors and genetics. The identification of genes that place people at risk of suicide remains elusive, but data are rapidly evolving. In this narrative review, we describe how Tryptophan hydroxylase (TPH) genes, particularly TPH1 and TPH2, have been associated with suicide in various publications. There is also replicated evidence linking the brain-derived neurotrophic factor gene to suicide, with its most consistent results originating from epigenetic studies. Not surprisingly, many genes involved in the hypothalamic-pituitary-adrenal axis have been connected with suicide, but these data require replication. Finally, among the inflammatory genes studied in suicide, only specific polymorphisms in TNF-alpha and IL-6 may increase susceptibility to suicidal behavior. In conclusion, significant work remains to be performed as inconsistencies undermine the reliability of genetic results in suicide. Potential avenues for future research are proposed.

PMID:40282388 | DOI:10.3390/genes16040428