Rs1229984 is a non-synonymous variant thought to have a functional role. In vitro studies predicted up to 40 times higher enzymatic activity comparing carriers versus non-carriers of the A allele (26), resulting in faster accumulation of plasma acetaldehyde. This would be aversive, and it is the principle of action of the drug disulfiram, used for treating chronic alcohol dependence (http://www.bnf.org/bnf/bnf/current/3687.htm). However, the evidence for in vivo effects is limited, possibly because of lack of power arising from a combination of small sample sizes and low prevalence of the variant. A study conducted among 109 Jewish university students in the USA (MAF = 18.5%), reported that carriers of the A allele exhibited higher alcohol elimination rates (48). However, this locus contributed little to the total variance explained by genetic variation in the whole ADH region in a study of blood and breath ethanol levels among 412 Australian twins (27), and similarly a larger and more recent study of ADH variation and alcohol metabolism among 812 Australian twins and relatives (MAF = 3.5%) could not find sufficient evidence for an effect of
