The genome-wide significant SNPs reaffirm the importance of functional variants affecting alcohol metabolism to the risk of AD. The top association in ADH1B, rs1229984, is a missense variant that is amongst the most widely studied in relation to alcohol use, misuse and dependence8–10. The resulting amino acid substitution (Arg48His) increases the rate at which alcohol dehydrogenase 1B oxidizes ethanol to acetaldehyde8. Studies on Asian populations in which the derived allele is common demonstrated strong protection against the development of AD8,9,13. In EU and AA, the protective allele is present at much lower frequencies (EU MAF = 0-4%, AA MAF < 1%), nevertheless, recent large-scale studies have shown an association between this locus and alcohol consumption and problems at GWS levels in EU with similar effect size8–10. The lead variant in AA cohorts, rs2066702 (Arg370Cys), is another functional missense variant in ADH1B, and it also encodes an enzyme with an increased rate of ethanol oxidation8. The allele encoding Cys370 is common in AA, but rare in other populations8. Our results clearly show that these two different functional SNPs in ADH1B both
