The study has other limitations. First, only European populations were included; therefore, the genetic architecture of PAU in other populations remains largely unknown. To date, the largest non-European sample to undergo GWAS for alcohol-related traits is African American (AA), which was reported in the MVP phase1 sample (17,267 cases; 39,381 controls, an effective sample size of 48,015), with the only associations detected on chromosome 4 in the ADH gene locus (where several ADH genes map) [3]. The collection of substantial numbers of non-European subjects will require a concerted effort by investigators in our field. Second, despite the high genetic correlation between AUD and AUDIT-P, they are not identical traits. We conducted a meta-analysis of the two traits to increase the power for the association study of PAU, consequently, associations specific to AUD or AUDIT-P could have been attenuated. Third, there was no opportunity for replication of the individual novel variants. Because the variants were detected in more than 430,000 subjects and have small effect sizes, a replication sample with adequate power would also have to be very large, and no
