A Study of Candidate Genes Associated with Suicide Attempts in the Kazakh Population in Astana, Kazakhstan

Suicidal behavior is a multifactorial and highly heritable phenotype; however, data concerning its genetic determinants in disparate ethnic groups remain limited. Genes implicated in serotonergic neurotransmission and stress response regulation are regarded as primary candidates for elucidating biological vulnerability to suicide. The objective of this study is to investigate the relationship between suicide attempts and candidate gene polymorphisms in an ethnically homogeneous Kazakh population from Astana, Kazakhstan. The study's sample population comprised 126 patients with a documented history of suicide attempts and 120 age- and gender-matched controls without a history of suicidal behavior. A comprehensive genotyping analysis was conducted, encompassing polymorphisms in genes associated with serotonergic signaling, stress response, and neuroplasticity (<i>TPH1</i>, <i>TPH2</i>, <i>HTR2A</i>, <i>MAOA</i>, <i>SLC6A4</i>, <i>ANKK1</i>, <i>BDNF</i>, <i>COMT</i>, <i>CXCL8</i>, <i>SKA2</i>, and <i>FKBP5</i>). The associations were assessed across several genetic models, using odds ratios with 95% confidence intervals. A substantial correlation was identified between the <i>HTR2A rs6311</i> polymorphism and suicide attempts. The CC genotype exhibited a protective effect (<i>p</i> = 1.36 × 10^-5), while the TT genotype was associated with an elevated risk (OR = 3.16; 95% CI: 1.72-5.81). The association remained robust after stratification by sex, with an even stronger effect observed in women (OR = 4.70; 95% CI: 2.08-10.64). A nominal sex-specific association was observed for the <i>SKA2 rs7208505</i> variant, suggesting a potential role in stress-response mechanisms in women; however, this association was no longer statistically significant after adjustment for multiple comparisons. These results identify <i>HTR2A rs6311</i> as a potential genetic marker of suicide risk in the Kazakh population and support the involvement of serotonergic receptor regulation in the biological mechanisms underlying suicidal behavior. The results underscore the significance of sex-specific genetic influences, thereby enhancing our understanding of the polygenic underpinnings of suicidality.