not feasible to perform a sufficiently large number of permutations to obtain empirical P values. Instead, we obtained the lower and upper bounds assuming no linkage disequilibrium (LD) and very high LD, respectively, among the SNPs. When we assumed no LD, the P value was so small that the statistical test in the R package returned a 0; when we assumed an extremely high LD between the SNPs, we obtained P=2.0×10−4. Thus, even in the most conservative scenario, the test indicated significant enrichment of small P values in the replication. We also performed sign tests that examined whether the direction of effects was similar in the GWAS meta-analysis and the replication study. Of the SNPs with replication values of P<.01, the proportion of SNPs that had the same direction of effect of 89% (P=2.20×10−16; 95% CI, 82%–94%) for the combined ancestry group and 93% (P=2.20 10−16; 95% CI, 88%–97%) for European subjects. Again, in both cases the statistical test in the R package returned a 0, indicating that this pattern was almost impossible to occur by change. The mean odds ratios of these SNPs were 1.2 and 1.3 in the combined and European study samples, respectively. Overall, our findings confirm
