Identifying the causal variants located on 4q23 will prove to be challenging because of the low MAF of the variants associated with alcohol consumption in this region. Previous studies have shown that rs1229984 in ADH1B, which is associated with rapid alcohol metabolism, is strongly protective against high alcohol consumption.10 It is possible that the low-frequency variants identified in 4q23 are tagging rs1229984. However, rs1229984 deviated from HWE in the UKB (HWE P=1.5 × 10−78) and therefore was not analysed as part of the GWAS. The rs29001570 in ADH5 clearly represents an independent locus as the r2 with the other SNPs in 4q23 is <0.01. We believe this is the first GWAS of alcohol consumption to detect genome-wide significant association with ADH5, although a GWAS of alcohol dependence found suggestive evidence of association with PDLIM5 that is adjacent to ADH5.12 ADH5 is a formaldehyde dehydrogenase with low affinity for alcohol and therefore its role in alcohol metabolism and consumption is as yet unknown. rs145452708 that is located in the region between ADH1B/ADH1C and rs35081954 is a common variant located in intron
