enhancers are less likely to be shared across many tissues compared with those in promoters28, and that cell-type-specific eQTLs are more dispersedly distributed around the transcription start site than eQTLs affected expression in multiple cell types29,30. These results seem to indicate that tissue-specific eQTLs are enriched in distal regulatory elements (i.e., enhancers). To address this hypothesis, we computed the statistics to test for the between-tissue difference in eQTL effect (denoted by TD) and tested the inflation (or deflation) of mean TD of cis-eQTLs in the functional categories annotated by the Roadmap Epigenomics Mapping Consortium (REMC)31 (Methods). The result showed that although cis-eQTLs are enriched in genomic regions of active chromatin state (e.g., promoters and enhancers) and deflated in inactive regions, the mean TD of cis-eQTLs between CMC and GTEx-blood was almost evenly distributed across all the functional categories with no evidence of inflation in the enhancer regions (Fig. 2). The result remained largely unchanged if we repeated the enrichment analysis based on TD between GTEx-cerebellum and GTEx-blood (Supplementary Fig. 13). Note that these results do not contradict the observation from a recent study that eQTLs detected in specific tissues in GTEx tend to be most enriched among the variants predicted
