Frank et al. (2012) performed a GWAS with over 400,000 SNPs in a German sample of 1,333 men with severe AD and 2,168 controls, including 487 cases and 1,358 controls from Treuitlen et al. (2009). Testing for an association of AD case-control status, they identified one SNP that was GWS (rs1789891, P=1.27 × 10−8). Interestingly, the SNP is located in the region between ADH1B and ADH1C, two alcohol metabolizing enzyme genes and in complete linkage disequilibrium (LD) with a missense polymorphism in ADH1C (rs1693482, D’=1.0, r2=0.27). Although this study replicated a finding in the COGA sample (P=0.015), it did not replicate the top (non-GWS) findings in either the COGA (Edenberg et al., 2010) or SAGE (Bierut et al., 2010) datasets. This was the first AD GWAS to identify a GWS association in the discovery sample that was replicated in an independent sample and the first to identify significant associations in alcohol metabolizing enzyme genes, importantly replicating the findings from candidate gene studies (Thomasson et al., 1991; Chen et al., 1999; Edenberg, 2007, Bierut et al. 2012).
