Overall, we observed much greater tissue specificity for trans-eQTLs than a set of FDR-matched cis-eQTLs (Fig. 2c); this observation was robust to choices of m value threshold and selection criteria for matching cis-eQTLs (Extended Data Fig. 8d–g). While 3.8% of trans-eQTLs were shared across three or more tissues at m > 0.9, 25.3% of FDR-matched cis-eQTLs were shared. The extensive tissue-specificity of trans-eQTLs was also supported by a hierarchical approach for FDR control17, where we found no trans-eQTLs shared across more than one tissue (Extended Data Table 3). Our estimate of increased tissue specificity for trans-eQTLs agreed with the minimal sharing of trans effects reported in previous eQTL studies with fewer tissues4,19, and greatly exceeds what would be expected on the basis of replication between tissues for cis-eQTLs of matched minor allele frequency (MAF) and effect size (Wilcoxon rank sum test; P ≤ 2.2×10−16 for all choices of replication FDR; Extended Data Fig. 8h). Given the greater tissue-specificity of trans-eQTLs, we note that heterogeneity in cellular composition of bulk tissue samples is one important confounder that may reduce power to
