The ADH1B gene has been previously associated with MaxDrinks and related alcohol phenotypes in EA populations using linkage and candidate gene approaches. A genome scan of MaxDrinks identified significant loci in the 4q21.3 region (the maximal LOD=3.5), a region to which the ADH gene cluster maps. Drinkers with the ADH1B rs1229984*Arg48 allele were less likely to have a flushing response to alcohol (Bierut et al., 2012, Chen et al., 1999), report a higher Maxdrinks count (Bierut et al., 2012, Macgregor et al., 2009), and greater past year alcohol consumption (Macgregor et al., 2009, Edenberg, 2007) than those with the rs1229984*His48 allele. Consistent with earlier studies (Bierut et al., 2012), the genome-wide significance of rs1229984 in the current study was 10-15 in EAs, reflecting a relatively large effect size (β= -0.25). The individuals with His48 allele reported less Maxdrinks in EA population from our Yale-UPenn samples (Fig 4). Rs2066702, also at ADH1B, has not previously been associated with MaxDrinks, likely because of its low frequency in EAs and Asians, who are most heavily represented in studies of ADH1B variants and alcohol
