rs1229984

This genome-wide association study investigated the genetic basis of alcohol dependence (AD) in 7,842 Dutch participants using the AUDIT screening measure. Twin-based heritability was estimated at 60% (95% CI: 55-69%) and common SNPs explained 33% of this heritability. The GWAS identified four suggestive loci (4q34.1, 2p16.1, 6q25.3, 7p14.1) with the strongest association at rs55768019 (P=7.58×10⁻⁷, OR=0.80). Replication confirmed known AD variants: rs1229984 in ADH1B (P=1.58×10⁻⁴, OR=1.77) and rs7119734 in DSCAML1 (P=7.5×10⁻³, OR=1.16).

Genome-wide association study of alcohol dependence and related phenotypes in 313 males from extended Han Chinese pedigrees in Northern Hunan Province. ALDH2 rs671 (Glu504Lys) was identified as the major genetic determinant, with genome-wide significant associations for alcohol dependence (p=4.73×10⁻⁸), maximum drinks in 24 hours (p=1.54×10⁻¹⁶), and facial flushing response (p=4.75×10⁻²⁶). The rs671 variant explained 7.9% of AD phenotypic variation, 22.9% of maximum drinks variation, and 29.2% of flushing response variation. A previously reported candidate SNP rs10774610 in CCDC63 was confirmed but shown to result from linkage disequilibrium with ALDH2.

A case-control study of 2,139 esophageal squamous cell carcinoma (ESCC) cases and 2,273 controls in a Chinese population examined six SNPs previously associated with upper aerodigestive tract cancers in Europeans. Four SNPs showed significant association with ESCC risk: rs1494961 at 4q21 (OR=1.15, 95% CI=1.05-1.26), rs1229984 in ADH1B at 4q23 (OR=1.24, 95% CI=1.13-1.36), rs1789924 near ADH1C at 4q23 (OR=1.20, 95% CI=1.03-1.39), and rs671 in ALDH2 at 12q24 (OR=0.83, 95% CI=0.75-0.91). Combined analysis showed significant allele-dosage effects with individuals carrying 5+ risk alleles having 1.76-fold increased ESCC risk.

A meta-analysis of two genome-wide association studies (COGA and SAGE) identifying genetic variants associated with maximum number of alcoholic drinks consumed in 24 hours (maxdrinks). The study combined 4,915 participants of European descent and found suggestive associations with multiple loci including rs1229984 (ADH1B, p=2.04×10⁻⁸), rs4758317 (LMO1, p=7.2×10⁻⁷), and variants in PLCL1 (p=4.07×10⁻⁶). Approximately 40% of the variance in maxdrinks was explained by genome-wide SNPs.

This GWAS and replication study in a Korean cohort identified genetic associations with alcohol dependence (AD), with the ADH gene cluster on chromosome 4q22-q23 and ALDH2 on 12q24 showing the strongest signals. The most significant finding was ADH1B rs1229984 (H47R) with p=2.63×10⁻²¹ and OR=2.35 in the replication cohort of 975 subjects. Conditional analyses revealed that ADH1B rs1229984 is likely the sole functional marker driving effects across the ADH cluster.

Population-based case-control study in China examining alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms in esophageal cancer. ADH1B rs1229984 G-allele showed significant association with esophageal cancer risk (OR=1.34, dominant model), and ALDH2 rs671 showed significant gene-environment interaction with alcohol consumption, with moderate/heavy drinkers carrying ALDH2 A allele and ADH G allele at highest risk. No association found for ADH1C rs698 polymorphism.

This case-control study of 457 Caucasian males (200 alcohol abusers, 257 controls) found that alcohol abusers had significantly shorter peripheral blood leukocyte telomere length (TL was 0.42 vs. 0.87 relative T/S ratio, P<0.0001), suggesting accelerated cellular aging. The ADH1B rs1229984 (Arg47His) genotype modulated this association: carriers of the ADH1B*2 allele were protected from alcohol abuse (OR=0.28, 95% CI 0.14-0.55) and showed longer telomeres, while ADH1B*1 carriers exhibited shorter telomeres and higher alcohol consumption. The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with telomere length.

ADH1A genetic variation predisposes to personality traits and substance dependence across multiple population groups. Agreeableness and Conscientiousness were associated with ADH1A diplotypes, haplotypes, and genotypes in European-American and African-American subjects (p range: 1.7×10⁻⁴ to 0.055), with effects modified by sex and age. Substance dependence was significantly associated with ADH1A variants (p range: 0.008 to 0.060), suggesting ADH1A's role in both personality phenotyping and addiction vulnerability.

Hospital-based case-control study of 1,110 SCCHN cases and 1,129 controls examining alcohol dehydrogenase gene polymorphisms. ADH7 A92G (rs1573496: C>G) GG and combined CG+GG genotypes were associated with decreased SCCHN risk (adjusted OR 0.32, 95% CI 0.13-0.82 for GG; adjusted OR 0.74, 95% CI 0.59-0.94 for CG+GG). ADH1B R48H (rs1229984: G>A) showed no overall association with SCCHN risk in this non-Hispanic White population.