the Japanese was then related to the “atypical” form of acetaldehyde dehydrogenase deficiency (Harada, Agarwal, & Goedde, 1981) and, finally, to the ALDH2*2 allele of the gene coding for the β2 subunit of the enzyme (Goedde, Agarwal, & Harada, 1983). Variants in genes involved in alcohol metabolism leading to increases in acetaldehyde either through the increased oxidation of alcohol to acetaldehyde (ADH1B) or through slowing the rate of conversion of acetaldehyde to acetate (ALDH2) have been associated with quantitative differences in alcohol consumption (Crabb, Edenberg, Bosron, & Li, 1989; Luczak, Glatt, & Wall, 2006; Peng & Yin, 2009). Obviously, these resistance genetic effects are discoverable only in samples examining use variation in those who have tried drinking. Consequently, the use of exposed controls has become a more common approach in substance abuse genetics. It should be noted, however, that while exposed controls facilitate the detection of factors related to elevated risk for physical dependence, the factors – including genetic ones – that lower the probability of drug exposure and thus enhance resistance are undetectable with this sampling scheme. To a large degree, the same pertains to the factors that influence the magnitude of exposure (usually limited to a substantial but
