Our most significantly associated SNP was the synonymous coding variant in exon 5 (rs279858) which has previously been found to be associated with AD status (Covault et al., 2004; Edenberg et al., 2004; Fehr et al., 2006; Lappalainen et al., 2005) and subjective intoxication (Haughey et al., 2008; Pierucci-Lagha et al., 2005). In our data, the frequency of the rs279858 G allele was lower in DSM-IV diagnosed alcoholics (41.5%) compared to non-alcoholic twins (43.7%) and was, as expected, related to a lower DSM-IV factor score and number of DSM-IV AD symptoms experienced by each twin. The direction of effect is opposite to that reported by Pierucci-Lagha and colleagues (2005) where individuals carrying G alleles were less sensitive to the effect of alcohol and hence more likely to become alcohol dependent and in three studies where the G allele was significantly over-represented among alcoholics (Covault et al., 2004; Fehr et al., 2006; Lappalainen et al., 2005). In each of these studies the frequency of the G-allele ranged from 34 to 42% in the control samples - a frequency similar to that
