To further dissect the associations between genomic elements and QTLs, we compared all of the different types of QTLs with one another and with genomic annotations (Fig. 4E). As expected, eQTLs tended to be enriched at promoters, and cQTLs, at enhancers and transcription factor (TF)–binding sites; fQTLs were spread over many different elements. Also, an appreciable number of eQTLs were enriched on the promoter of a different gene from the one regulated, suggesting the activity of an Epromoter, a regulatory element with dual promoter and enhancer functions (41). For the overlap among different QTLs, we expected that most cQTLs and fQTLs would be a subset of the much larger number of eQTLs; somewhat surprisingly, an appreciable number of these did not overlap (Fig. 4F). To evaluate this precisely, we calculated π1 statistics and found that the cQTL overlap was larger than the fQTL overlap (0.89 versus 0.11). Moreover, eQTL-cQTL overlaps often suggested that the expression-modulating function of an eQTL derived from chromatin changes (e.g., for MTOR) (Fig. 4F). Overall, the total number of overlapping QTLs was 2477 (which we dub multi-QTLs) (Fig. 4F).
