Significant LD was found in the region of the gene cluster composed of the ADH6, ADH1A, ADH1B, ADH1C, and ADH7 genes (Figure 6). The first four genes were in a strong LD structure and two of them (the ADH1A and ADH1B genes) were in the same haplotype block, which implied that the contribution of the genes that make up the cluster to the associated effect on substance use may not be independent. One study(Osier et al. 1999) claimed the ADH1C association might be attributable to the ADH1C gene being in close proximity to the ADH1B gene on chromosome 4q so that their genotypes are correlated. Our results showed that ADH1C is in another haplotype block (multiallelic D’ = 0.99) although it is physically close to ADH1B (multiallelic D’ = 0.6). It is still necessary to investigate further the polymorphisms that are in the same haplotype block with ADH1C (e.g., the nonsynonymous SNPs shown on the LD plots and supplementary Table 11) or the polymorphisms on close genes within this strong LD structure. The LD plots are shown for the Asian and European populations in Figure 6 and supplementary Figure 12, respectively.
