We then sought to study the genome-wide regulatory behavior of our LCL trans-SNPs (P<5×10-8) using the calculated π1 values in our replication cohorts (ALSPAC and Oxford-TwinsUK) (Supplementary Table 4). In total 314 trans-SNPs with π1 ≥ 0.10 in the MuTHER discovery cohort were tested of which 61 (19%) and 43 (14%) also have π1 estimates of ≥ 0.10 in the ALSPAC-LCL and/or Oxford-LCL replication cohort, respectively. When comparing not only the π1’s in the replication cohorts but also the top 1000 vs. bottom 1000 associated transcripts for each of the 61 and 43 trans-SNPs, respectively, we find a highly significant enrichment for lower P-values in the top 1000 transcripts (Mann-Whitney, ALSPAC P = 2.6 × 10−6 and Oxford P=3.8 × 10−5). This indicates that not only the genome-wide regulatory behavior but also the ranking of associated genes for a subset of trans-SNPs is consistent across studies but larger sample sizes are needed to confirm the observed effect of gene regulation.
