Noncoding variations in ADH genes affect the risk for alcoholism. A study of 110 SNPs across all seven ADH genes demonstrated that variations in ADH4 most strongly affected risk for alcoholism in European-American families (Edenberg et al. 2006). The variations extended across the entire gene, with the strongest evidence coming from SNPs located between the intron closest to the start of the gene and a region nearly 20,000 bp beyond the end of the ADH4 gene. Independent studies (Guindalini et al. 2005; Luo et al. 2005, 2006) have confirmed this finding. Non-coding SNPs in the ADH1A and ADH1B genes also appear to be associated with alcoholism risk in the European-American family sample (Edenberg et al. 2006). Variants in ADH1C have been associated with risk in Native Americans (Mulligan et al. 2003). Variations in the ADH7 gene may affect the risk for alcoholism through interactions with other variants (Osier et al. 2004). Finally, a recent study (Birley et al. 2005) indicated that there is an important site in the region containing the ADH genes that affects alcohol metabolism but is not related to the coding variations in ADH1B or ADH1C.
