To prioritize trans-eQTLs caused by intracellular mechanisms (i.e. gene regulation within cells), we applied several analytic strategies (Supplementary Note). Replication in purified cell types and cell lines identified 4,018 (6.7%) trans-eQTLs that replicated in at least one dataset or were supported by DNA methylation QTL data (Benjamini-Hochberg FDR<0.05; 93.3% average allelic concordance; Supplementary Note, Supplementary Figure 5, Supplementary Data 2). The replication rate in GTEx23 tissues was very low (discovery without GTEx, 0.07% of trans-eQTLs replicated in any non-blood tissue, 0.09% in blood, Benjamini-Hochberg FDR<0.05) but the allelic concordance of significant effects was, on average, 66% in non-blood tissues and 100% in blood (Supplementary Data 3). Despite these low replication rates, trans-eQTLs showed an inflation of replication signal in the majority of tissues (Supplementary Figure 6a), most notably in whole blood, esophagus muscularis, liver, heart atrial appendage and non-sun-exposed skin.
