We also performed replication studies of the single trans-loci identified at P< 5×10−8 in independent data sets (Supplementary Table 4) and noted that the replication rate of trans-associations was strikingly lower compared to cis-effects (Supplementary Fig. 3, Table 3) with π1 estimates ranging from 0.0002-0.13 compared to π1 of 0.34-0.76 for cis-replication. However, using a P-value cutoff of <0.05 and taking direction of effect into account we found an up to 3-fold enrichment of replicated trans-eQTLs (Table 3, Supplementary Table 10). Taken together, trans-regulatory effects of gene expression are highly complex with small effect sizes indicating that samples sizes are required to be larger than previously expected.
