Analysis of well-characterized loci that were previously proposed in candidate gene studies in a large GWA study on alcoholism, SAGE, reveals unimpressive differences between cases and controls at most loci. The frequently studied variants associated with alcoholism in DRD2, ADH1C, OPRM1 and COMT demonstrate insignificant frequency differences in SAGE (p>.05, Table 2). Although several studies implicate a biological role of these variants in alcoholism (Blum et al., 1990; Bond et al., 1998; Hendershot et al., 2011; Ponce et al., 2008; Thomasson et al., 1991; Tiihonen et al., 1999; Tolstrup et al., 2008; Zhang et al., 2006), our results reveal that these variants are not strongly associated with alcoholism in European and African ancestry populations. The only candidate that modestly replicated in SAGE, rs279858 in GABRA2, had a p-value of 0.0052 (OR=1.572). This finding was anticipated because a previous GWA study on the SAGE dataset demonstrated a similar association (Bierut et al., 2010). The replication of rs279858 in SAGE provides some support for future studies focused on the function of this variant and associated variants in GABRA2 (Edenberg et al., 2004).
