variant (Edenberg 2007) corresponding to the protective allele C of rs1789891 in the present GWAS was indeed found to be the protective allele in our sample. However, the association with Arg272Gln, (p=1.24E-7, OR=1.31) was not stronger than the association with rs1789891 (p=1.27E-8; OR=1.46). It therefore remains uncertain whether the observed association was due to the effect of the Arg272Gln. The SNP rs1789891 is located intergenically, in a region in which many SNPs are in high LD (Figure 4). Previous studies have shown that several variants in the ADH cluster, which are in LD with one another (Edenberg 2007), contribute independently to the risk of AD (Macgregor et al. 2008). The present findings are consistent with this observation. Apart from Arg272Gln, six of the 13 top SNPs with p<1E–5 were located within or around the ADH1C gene and were in LD with one another (D′ between 0.61 and 1.0) and the conditional analysis showed small rs1789891-independent effects (Table 1).Even in the absence of definite functional evidence for the association with rs1789891, this finding is relevant as it receives independent support from the COGA study, which found association with AD for the same allele (p=1.47E–2, OR=1.31).
