As the PGC cohort is substantially smaller than the 23andMe single cohort, power in the PGC MDD GWAS to detect the effect sizes for the two genome-wide significant loci observed in the preliminary 23andMe GWAS was less than 0.6 at a nominal level of significance (p<0.05 uncorrected), and the analogous power to replicate the remaining 23andMe loci in PGC declined thereafter19. However, the probability of PGC showing the same direction of effect in 23andMe exceeded 90% for each of the top ten independent 23andMe loci that were also evaluated in PGC (corresponds to all overlapping peak-pruned 23andMe loci with unadjusted p < 1.0×10−7 in 23andMe). We therefore conducted a sign-test examining concordance between PGC effect direction and the 23andMe effect direction for the top overlapping 23andMe peak loci. Nine of the top 10 loci matched sign, (Fisher’s exact test p = 0.033). The test continued to deviate significantly from chance at a range of thresholds, suggesting consistent signal between the PGC results and 23andMe. For the 82 independent SNPs with nominal p-values less than 1×10−5 in 23andMe, the p-value for
