Alcohol dependence (AD) is a moderately heritable disorder for which two major families of risk genes have been mapped via linkage and candidate gene association studies: the alcohol dehydrogenase (ADH) family, which contributes to variation in speed of ethanol metabolism and yields a variable concentration of acetaldehyde following alcohol consumption; and the aldehyde dehydrogenase (ALDH) gene family, which mediates acetaldehyde clearance (Edenberg 2007; Li et al. 2011, 2012a, 2012b). Genes in the latter family, primarily ALDH2, are associated with the flushing reaction seen in some East Asian populations (Thomasson et al. 1993). These variants have substantial public health importance beyond their relationship to flushing and AD, as acetaldehyde exposure is also a key risk factor for gastrointestinal tract neoplasms (Mikko 2012) and the flushing response itself is a indicator of esophageal cancer risk (Brooks et al. 2009). While these two gene families have been the focus of many studies, there remains significant unexplained genetic variation in AD.
