Research output: Contribution to journal › Article › peer-review
Genetic analysis of alcohol use disorder : GWAS of alcohol use disorders identification test (AUDIT) and polygenic risk scores in an east slavic population. / Trofimov, Michil; Kudriavskii, Viacheslav; Shaheen, Layal; Kovalenko, Elena; Vergasova, Kate; Kamelin, Alexey; Rubinova, Valerya; Kharitonov, Dmitry; Kim, Anna; Plotnikov, Nikolay; Elmuratov, Artem; Gainetdinov, Raul R; Levchenko, Anastasia; Krupitsky, Evgeny; Kibitov, Alexander; Ilinskaya, Anna; Ilinsky, Valery; Rakitko, Alexander.
In: Drug and Alcohol Dependence, Vol. 273, 112713, 01.08.2025.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Genetic analysis of alcohol use disorder
T2 - GWAS of alcohol use disorders identification test (AUDIT) and polygenic risk scores in an east slavic population
AU - Trofimov, Michil
AU - Kudriavskii, Viacheslav
AU - Shaheen, Layal
AU - Kovalenko, Elena
AU - Vergasova, Kate
AU - Kamelin, Alexey
AU - Rubinova, Valerya
AU - Kharitonov, Dmitry
AU - Kim, Anna
AU - Plotnikov, Nikolay
AU - Elmuratov, Artem
AU - Gainetdinov, Raul R
AU - Levchenko, Anastasia
AU - Krupitsky, Evgeny
AU - Kibitov, Alexander
AU - Ilinskaya, Anna
AU - Ilinsky, Valery
AU - Rakitko, Alexander
N1 - Copyright © 2025. Published by Elsevier B.V.
PY - 2025/8/1
Y1 - 2025/8/1
N2 - 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.
AB - 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.
KW - Adult
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Alcoholism/genetics
KW - Cohort Studies
KW - Genetic Risk Score
KW - Genome-Wide Association Study/methods
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Eastern European People/genetics
KW - Genome-wide association study (GWAS)
KW - Alcohol use disorder (AUD)
KW - Polygenic risk scores (PRSs)
KW - Genetic correlations
UR - https://www.mendeley.com/catalogue/eff16c5e-6ded-34a6-b8da-fc66b3903392/
U2 - 10.1016/j.drugalcdep.2025.112713
DO - 10.1016/j.drugalcdep.2025.112713
M3 - Article
C2 - 40440926
VL - 273
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
SN - 0376-8716
M1 - 112713
ER -
ID: 136195484