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

Tatayeva R. Tussupova A. Nursafina A. Zholdybayeva E. Bazarbayeva Z. Fedorenko O. Sembaeva Z. Tulembaeva A. Sarkulova S. Karimbayeva B.
March 2026 Multidisciplinary Digital Publishing Institute (MDPI)

International Journal of Molecular Sciences
2026 #27 Issue 5

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 (TPH1, TPH2, HTR2A, MAOA, SLC6A4, ANKK1, BDNF, COMT, CXCL8, SKA2, and FKBP5). The associations were assessed across several genetic models, using odds ratios with 95% confidence intervals. A substantial correlation was identified between the HTR2A rs6311 polymorphism and suicide attempts. The CC genotype exhibited a protective effect (p = 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 SKA2 rs7208505 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 HTR2A rs6311 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.

candidate genes , genetic polymorphisms , HTR2A , hypothalamic–pituitary–adrenal axis , Kazakh population , molecular psychiatry , serotonergic system , sex-specific effects , SKA2 , stress reactivity , suicidal behavior , suicide attempts

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Department of General Biology and Genomics, L.N. Gumilyov Eurasian National University, Astana, 010000, Kazakhstan
Department of Technology and Standardization, K. Kulazhanov Kazakh University of Technology and Business, Astana, 010000, Kazakhstan
National Scientific Shared Laboratory of Biotechnology, National Center for Biotechnology, Astana, 010000, Kazakhstan
Mental Health Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 643000, Russian Federation
Ministry of Defense of the Republic of Kazakhstan, Astana, 010000, Kazakhstan
Institution of NJSC “Astana Medical University”, Astana, 010000, Kazakhstan
Department of Social and Humanitarian Disciplines, Kazakh National University of Arts, Astana, 010000, Kazakhstan

Department of General Biology and Genomics
Department of Technology and Standardization
National Scientific Shared Laboratory of Biotechnology
Mental Health Research Institute
Ministry of Defense of the Republic of Kazakhstan
Institution of NJSC “Astana Medical University”
Department of Social and Humanitarian Disciplines

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