The SNP showing genome-wide significance in the present study is located in the region harboring the ADH gene cluster. This is the most consistently reported region in linkage analyses (Prescott, Sullivan, Kuo et al. 2006), and has shown evidence of association in a number of candidate gene studies of AD (Birley, James, Dickson et al. 2009). Existing knowledge of the biochemical function of the ADHs and the results of animal studies provide further strong support for the hypothesis that the ADHs are involved in the etiology of AD. The ADHs are involved in the enzymatic degradation of ingested ethanol, a process which results in the toxic intermediate acetaldehyde (Edenberg 2007). This is normally metabolized rapidly to acetate, in a reaction that is catalyzed by the aldehyde dehydrogenases (ALDHs). Accumulation of acetaldehyde in the blood causes the so called “flushing reaction”, which leads to the avoidance of alcohol consumption. This is the rationale for the use of the ALDH inhibitor disulfiram in the treatment of AD (Edenberg 2007; Petersen 1992; Suh, Pettinati, Kampman et al. 2006). A naturally occurring reduction in
