Four GWASs of alcohol dependence and two of alcohol consumption now have been completed in populations of European ancestry. In the first of these, Treutlein and colleagues (2009) found several SNPs with P values in the range of 10−6; upon pooling with a replication sample, two of these SNPs, rs7590720 and rs1344694, showed statistical significance in the combined male-only sample of 1,460 alcohol-dependent subject and 2,332 community control subjects. These SNPs are located in a region of the long arm of chromosome 2 where prior linkage studies have identified increased allele-sharing for alcoholism. The gene closest to the association signal, PECR (which encodes the enzyme peroxisomal trans-2-enoyl-CoA reductase) is involved in the metabolism of fatty acids, particularly during deprivation when energy expenditure transitions from carbohydrates to fatty acids. In addition, the investigators noted that a SNP called rs1614972 in the ADH1C gene was strongly associated with alcohol dependence (P = 1.4 × 10−4) even though it did not meet strict standards for genome-wide multiple testing. Two subsequent studies have identified a SNP in PKNOX2 (rs10893366, P = 1.9 × 10–7)
