The patterns of sharing were also supported by replication between single-tissue cis-eQTLs, estimated by π1 (the proportion of true positives16) among the eQTLs identified in one tissue and then tested for replication in a second tissue (Extended Data Fig. 7a, median π1 = 0.740). The patterns held even when accounting for variable number of overlapping donors among pairs of tissues in the GTEx study design (Extended Data Fig. 7b–e). cis-eQTLs exhibited a distinctly bimodal pattern of tissue sharing—they were likely to be either shared across most of the 44 tissues or specific to a small subset of tissues (Fig. 2b). This bimodality was further supported by three different methods: simple overlap of the single tissue eQTLs, a hierarchical multiple comparison procedure (treeQTL17), and an empirical Bayes model (MT-eQTL18; Extended Data Fig. 8a–c). Each method also demonstrated that cis-eQTLs discovered in tissues with larger sample sizes were more often tissue-specific; however, estimates of tissue-specificity for large sample-size tissues can be influenced by difficulty in replicating small effect-size eQTLs in tissues with fewer samples.
