rs975833

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).

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.

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.