We then characterized tissue dependency of regulatory effects in more detail using a matched co-twin design as previously described 11, comparing the p-value distribution of significant SNP-probe pairs within and across tissues (Supplementary Fig. 7).We found that 56-83% of cis-effects were shared across tissues with adipose and skin sharing more with each other than with LCLs (Table 1). eQTLs sharing statistical significance might still have tissue-dependent biological consequences if they have different effect sizes (fold change in expression) across tissues. Thus, we also evaluated tissue-dependency by contrasting expression fold changes between tissues and estimating the predictive value (r2) of each tissue against the other two (Supplementary Fig. 8). After accounting for winner’s curse (subtracted unexplained intra-tissue variance), we estimate that 41-62% of cis-eQTLs are not only tissue-independent but also have a similar magnitude of effect. Taken together, using several complementary approaches we find evidences pointing towards >60% of cis-eQTLs being statistically significant in multiple tissues.
