test; P ≤ 2.2×10−16 for all choices of replication FDR; Extended Data Fig. 8h). Given the greater tissue-specificity of trans-eQTLs, we note that heterogeneity in cellular composition of bulk tissue samples is one important confounder that may reduce power to detect trans-eQTLs, or even lead to false positive associations6. Despite the high tissue-specificity, we did observe a small number of tissue-shared trans-eQTLs, including rs7683255, which was moderately associated in trans with NUDT13 across most tested GTEx tissues with a consistent direction of effect (Extended Data Fig. 9a). We also found examples of trans-eQTLs shared across a subset of related tissues, such as an association between rs60413914 and RMDN3, a gene with increased expression levels in brain regions as compared to other tissue types, and for which the trans-eQTL had moderate effects in all tested brain regions but no strong effect in other tissues (Extended Data Fig. 9b, c).
