We applied a stringent definition of replication requiring the same SNP to have the same direction of effect in the replication study and meta-analysis. Table 1 (combined analysis) and Table 2 (European analysis) report the SNPs that replicated at P≤.005. The P values for all SNPs can be downloaded from http://www.people.vcu.edu/~ejvandenoord/. Compared with the meta-analysis or when combining P values from the 3 ancestral groups, sample size was ignored when calculating the overall P value across the replication study and meta-analysis. In the GWAS meta-analysis, the effect sizes will be overestimated and P values will be too optimistic owing to the winner’s curse.23–25 Furthermore, because the sample size was much larger in the meta-analysis, these P values would have dominated the combined P value. Ignoring samples sizes avoids overly optimistic P values while still providing some quantification for the combined evidence of a specific SNP across the meta- analysis and replication study. Some SNPs in Table 1 showed substantial allele frequency differences across ancestral groups. However, in addition to using nuclear families, the UNPHASED analyses were performed within each ancestral group to provide a second layer of protection against possible stratification effects.
