Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 1:273:112713.
doi: 10.1016/j.drugalcdep.2025.112713. Epub 2025 May 14.

Genetic analysis of alcohol use disorder: GWAS of alcohol use disorders identification test (AUDIT) and polygenic risk scores in an east slavic population

Michil Trofimov  1 , Viacheslav Kudriavskii  2 , Layal Shaheen  3 , Elena Kovalenko  4 , Kate Vergasova  4 , Alexey Kamelin  4 , Valerya Rubinova  4 , Dmitry Kharitonov  4 , Anna Kim  4 , Nikolay Plotnikov  4 , Artem Elmuratov  4 , Raul R Gainetdinov  5 , Anastasia Levchenko  5 , Evgeny Krupitsky  6 , Alexander Kibitov  6 , Anna Ilinskaya  7 , Valery Ilinsky  7 , Alexander Rakitko  8
Affiliations

Genetic analysis of alcohol use disorder: GWAS of alcohol use disorders identification test (AUDIT) and polygenic risk scores in an east slavic population

Michil Trofimov et al. Drug Alcohol Depend. .

Abstract

Background: Alcohol use disorder (AUD) significantly affects over 200 health conditions, causing about 3 million deaths annually worldwide and is approximately 50 % heritable.

Methods: We conducted a genome-wide association study (GWAS) on self-reported alcohol consumption and alcohol-related challenges (AUDIT score) in a large East Slavs cohort (N = 41,575). Genetic correlations with diverse phenotypes were assessed, and a polygenic risk score (PRS) for alcohol use disorder (AUD) was built and tested in an independent clinical cohort. GWAS and PRS associations were validated across various genetic ancestries.

Results: The East Slavs GWAS identified a highly significant association (p = 2.5 ×10-18) between the rs1229984 SNP and AUD. Transancestral modeling revealed significant associations in Ashkenazi Jews, Tatars, Siberian, and other populations. Additional subthreshold associations (p < 10-6) were found in SNPs within KIF26, OCA2, DLGAP2, and miRNA AL161421 gene regions. SNP-based heritability was estimated at hg = 6.4 % (SE = 1.1 %). Genetic correlation analysis revealed the strongest positive associations with psychiatric traits. We trained the PRS using external summary statistics and individual-level genomic data from our cohort (R2 = 0.013). It outperformed other external PRSs included in the analysis. Validation in the independent clinical cohort showed an AUC of 0.6 (95 % CI = 0.56-0.64), and integrating PRS with non-genetic models increased the AUC by 1.33 %, resulting in 0.762 (p = 8 × 10⁻⁵).

Conclusions: Our findings suggest a genetic basis for AUD involving genes related to alcohol metabolism and the reward system. The applicability of the PRS across diverse genetic ancestries supports its integration into non-genetic prediction models, enhancing AUD prediction accuracy in diverse populations.

Keywords: Alcohol use disorder (AUD); Genetic correlations; Genome-wide association study (GWAS); Polygenic risk scores (PRSs).

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

LinkOut - more resources