Variation at COMT, ADH1B-ADH1C and HTR2A is associated with substance use disorders in Ukrainians
Тип публікації :
Препринт
Дата випуску :
24 квітня 2026 р.
Автор(и) :
Олена Турос
eKNUTSHIR URL :
Журнал :
medRxiv
Цитування :
[APA 7] Олена, Т. (2026). Variation at COMT, ADH1B-ADH1C and HTR2A is associated with substance use disorders in Ukrainians. medRxiv,. https://doi.org/10.64898/2026.04.23.26351594
[ДСТУ] Олена Т. Variation at COMT, ADH1B-ADH1C and HTR2A is associated with substance use disorders in Ukrainians. medRxiv. 2026. DOI: 10.64898/2026.04.23.26351594 (дата звернення: 11.09.2026).
Abstract Background Substance use disorders (SUDs), including alcohol and drug dependence, and smoking, pose a public health threat with their high prevalence and comorbidity with other diseases, and contribution to mortality. SUDs are highly correlated, and their genetic background is shared to some degree. Objectives We aimed to investigate the genetic associations of previously reported loci for a wide range of SUDs in an unstudied Ukrainian population. Methods We collected data from 595 individuals (339 women, 253 men), including 321 participants from two rehab centres. Based on clinical review and questionnaire data we defined drug dependence, alcohol dependence, alcohol abuse, binge drinking, smoking, opiate, amphetamine, cannabis, and hallucinogen use, along with several intermediary alcohol use and smoking variables considering the amount of use and the level of dependence. We genotyped COMT -rs4680, ADH1B-ADH1C -rs1789891, and HTR2A -rs6313, and applied logistic and ordered logistic regression assuming an additive inheritance model, controlling for the recruitment group, other substance uses, age, and sex, in the association analyses. Results We replicate ( P <0.05) the associations at COMT -rs4680 with smoking status (OR[95% CI]=1.56[1.01-2.41], P =0.047) and heaviness (1.37[1.04-1.80], P =0.026), and at ADH1B-ADH1C -rs1789891 and HTR2A -rs6313 with alcohol dependence (1.69[1.03-2.76], P =0.038 and 0.66[0.47-0.92, P =0.016], respectively). Furthermore, we provide evidence for an association at HTR2A -rs6313 with hallucinogen use (0.58[0.35-0.98], P =0.040). Conclusion In this study on multiple SUDs we shed light on the genetic background of SUDs in Ukrainians and provide further evidence that variation at COMT is mainly associated with smoking, at ADH1B-ADH1C with alcohol-related variables, whereas HTR2A is a more general SUD-associated locus. Highlights We present the first genetic study of substance use disorders in Ukrainians We replicate the associations at COMT -rs4680 with smoking status and heaviness, and ADH1B-ADH1C -rs1789891 and HTR2A -rs6313 with alcohol dependence We provide evidence for an association at HTR2A -rs6313 with hallucinogen use
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