As variants in both ADH1C-rs698 and ADH1B-rs1229984 showed similar relationships with alcohol phenotypes, we constructed haplotypes with these two SNPs (SAS 9.2, HAPLOTYPE procedure, www.sas.com). Three haplotypes with frequencies >1% where found (rs698-rs1229984): A-A, A-G, and G-G. After removing 11 individuals with the rare haplotype (G-A), haplotypes were assigned with 100% certainty to all remaining individuals (N=1,118). Because haplotypes were assigned instead of estimated, deviations from HWE due to association (such as HW disequilibrium among AUD cases for rs1229984) should not lead to inaccurate haplotype assignment. To ensure this, we assigned haplotypes separately in cases and in controls, and found no differences. Haplotypes were combined into six diplotypes: A-A, A-A; A-A, A-G; A-A, G-G; A-G, A-G; A-G, G-G; G-G, G-G. These diplotypes were categorized to match the allelic risk model described above according to the level of risk they were hypothesized to confer. The diplotype hypothesized to confer high risk included the absence of the protective allele for both rs698 and rs1229984: G-G, G-G. Diplotypes hypothesized to confer intermediate risk included the absence of the protective allele for rs1229984 only:
