One of the most consistent findings among the several genetic linkage studies is evidence for a protective association for alcohol dependence and related behaviors on chromosome 4q near the alcohol dehydrogenase (ADH) gene cluster. In one genetic linkage study evaluating large families who were members of a Southwest Indian tribe, three loci near the ADH gene cluster showed evidence for linkage (Long et al., 1998). Additionally, genome screens for both the “unaffected by alcoholism” (Reich et al., 1998) and “maximum drinks ever consumed in a 24 hour period” (Saccone et al., 2001) phenotypes, provided evidence for linkage on chromosome 4 in the Collaborative Study of the Genetics of Alcoholism (COGA). Linkage at this site to various alcohol-related phenotypes has been confirmed by a genome screen in Mission Indian families (Ehlers et al., 2004), in Irish sib-pairs (Prescott et al., 2006), and in a population ascertained for smoking behaviors (Wilhelmsen et al., 2005). Linkage to this chromosome 4 site has also been found for use of tobacco phenotypes (Duggirala et al., 1999; Straub et al., 1999; Ehlers and Wilhelmsen, 2006).
