To assess the extent to which GTEx cis-eQTLs are responsible for common phenotypic variation, we applied co-localization analysis to examine local linkage disequilibrium and sharing of association signals using GWAS summary statistics across 21 traits42–44 (Supplementary Table 16). Among tested loci, 52% of trait-associated variants co- localized with an eQTL in one or more tissues (Fig. 5d, e). Importantly, no single tissue explained the majority of trait-associated loci, but the breadth of GTEx tissue sampling identified more co-localizations than any single tissue alone. Seven per cent and 93% of co-localizations are with lincRNA and protein-coding eGenes, respectively, suggesting that lincRNAs have a limited role in common disease pathogenesis. However, several findings complicate the interpretation of GWAS–eQTL overlaps. First, 26% of GWAS loci co-localize with more than one distinct eGene (that is, half of all co-localized loci). Second, GWAS co-localized eGenes are shared across an average of four tissues. Third, similar to lead eVariants, only 40% of GWAS signals co-localize with their nearest expressed gene, a finding that has important implications for the functional characterization of GWAS results.
