The most widely replicated linkage finding for alcohol dependence has been to a region on chromosome 4q containing the alcohol dehydrogenase (ADH) gene cluster. This region was originally implicated in the Collaborative Studies on the Genetics of Alcoholism (COGA) sample (Reich et al., 1998) and was replicated in two subsequent studies (Ehlers et al., 2004; Prescott et al., 2006). A second linkage region has been reported on chromosome 4p that contains a GABAA receptor subunit gene cluster (Long et al., 1998; Porjesz et al., 2002; Reich et al., 1998). Notably, candidate gene studies of the ADH and GABAA gene clusters have yielded significant evidence of association to alcohol dependence (Edenberg et al., 2004; Mulligan et al., 2003) further validating these linkage findings. Finally, linkage to a region of chromosome 1p has been reported in multiple studies (Hill et al., 2004; Reich et al., 1998). These results represent important progress in understanding the genetic influences that contribute to alcohol dependence, but it is important to note the difficulties in identifying such relations as there have been failures to replicate the evidence
