Table 2 Association results with multiple replications or genomewide significance and biological plausibility

From: The genetics of addiction—a translational perspective

Gene Summary
ALDH2 Glu504Lys (rs671) Decreased capacity to metabolize acetaldehyde to acetate leads to high concentrations of acetaldehyde, and the ‘alcohol flush reaction’,33 which decreases alcohol use and the risk of alcohol dependence (e.g.187, 188, 189)
ADH1B Arg48His (rs1229984) Increased rate of conversion of ethanol to acetaldehyde leads to slightly higher concentrations of acetaldehyde, with similar deterrent effects on alcohol use and alcohol dependence risk (e.g.188, 189, 190).
GABRA2 (rs279858, rs279826, rs279871) Repeatedly associated with alcoholism (e.g.36) although non-replications also exist (e.g.39, 191). Also associated with impulsivity and alcohol-related endophenotypes. SNPs are not functional but α2 subunit expression has been associated with binge drinking.138
DRD2/ANKK1 (Taq1A, rs1800497) Recognized as a risk factor for alcoholism.192 Meta-analyses find odds ratios ≈1.2 (P<0.001)193 −1.4, (P<0.00001),194 for the A1 allele. Considerable across-study heterogeneity exists.
CHRNA5/A3/B4 (rs16969968/rs1051780) Meta-analyses of GWAS88, 89, 90 and candidate gene91, 177 data show replicated association with cigarettes/day. Involved with receptor modification,195 sensitization and desensitization.196 Additional evidence for rs578776 as an independent signal177
CHRNB3-CHRNA6 (rs6474412) Evidence from a large GWAS but not as widely replicated.89
CYP2A6 (rs1801272) Impairs metabolism of nicotine to cotinine.197 Associated with cotinine levels and associated at genomewide significance with smoking in one study, with other studies yielding inconsistent results (e.g.89).
  1. Abbreviations: GWAS, gemonewide association study; SNP, single nucleotide polymorphism.