of ADH1B, the minor allele of which is common in that population and has been associated with alcohol dependence25. We also examined AUDIT-C scores in 167,721 MVP participants (57,677 AAs and 110,044 EAs)24, comparing the association of AUDIT-C scores and AUD diagnoses with the frequency of the minor allele of rs2066702 in AAs and rs1229984 (Arg48His) in EAs. Both polymorphisms exert large effects on alcohol metabolism39 and are among the genetic variants associated most consistently with alcohol-related traits in both AAs and EAs8,12,18. In both populations, we found a stronger association between age-adjusted mean AUDIT-C score and ADH1B minor allele frequency than between AUD diagnostic codes and the frequency of the minor alleles24. However, because AUD diagnoses accounted for unique variance in the frequency of the minor alleles in both populations, we concluded that the two phenotypes, although correlated, are distinct traits. Thus, in the present study, we used GWAS to examine these traits separately and to adjust for the effects of AUD in the AUDIT-C GWAS and the effects of AUDIT-C in the GWAS of AUD.
