The genes encoding alcohol dehydrogenase alpha, beta, and gamma subunits are organized as a gene cluster on chromosome 4q. Strong LD was found in the region of the gene cluster of the ADH6, ADH1A, ADH1B, ADH1C, and ADH7 genes (Figure S8 in Supplement 1), which were consistent with the studies by colleagues(76, 90). The first four genes were in a strong LD structure (large triangle in dark red and blue that was composed of multiple haplotype blocks), and ADH1A and ADH1B were in a same haplotype block, which indicated that the contribution of the gene cluster to the association effect on alcohol and drug dependence was not independent. Since ADH1B haplotypes have not been fully evaluated, it will be necessary for subsequent studies to investigate the roles of other polymorphisms in the same haplotype block (e.g., the nonsynonymous SNPs shown on the LD plot or in Table S10 in Supplement 1) or the polymorphisms on other genes within the strong LD structure. The LD plots are shown for the Asian and European populations in Figures S8 and S9 (see Supplement 1), respectively.
