Individual genome-wide association studies (GWAS) of AD have been relatively modest in size (but see a recent large publication using International Classification of Disease codes4) and have failed to identify consistently replicable loci 5, with the exception of variants within the alcohol metabolizing genes, notably ADH1B, and to a lesser degree, ADH1C. A recent large GWAS meta-analysis of 14,904 AD cases and 37,944 controls, which includes some of the samples used in this study, also only detected genome-wide significant (GWS) association with rs1229984 (Europeans) and rs2066702 (African-Americans); both SNPs are in ADH1B6. However, when examining a broader definition of alcohol use disorders from medical records, loci in additional genes have recently been identified4. We have previously conducted GWAS of AD-related phenotypes in smaller subsets of the data used in the present study, but results have eluded replication and power to detect rs1229984 has been low (e.g., for AD in a subset of 1884 unrelateds7, for AD, criterion count and criteria in 2010-2,322 individuals from 118 families8,9).
