Genome-wide association studies (GWAS) have discovered thousands of genetic variants associated with complex traits and diseases1–3. Most trait-associated variants reside in non-coding regions of the genome4,5, suggesting that genetic variants may affect the trait through regulation of gene expression6,7. With the advances in microarray and sequencing technologies, genome-wide genotype and gene expression data available from relatively large samples have been generated to identify genetic variants affecting transcription abundance8–10, i.e., expression quantitative trait loci (eQTLs). Current eQTL studies are biased toward the most accessible tissues (e.g., blood), which are often not the most relevant tissues to the traits and diseases of interest. The Genotype-Tissue Expression (GTEx) project11–13 provides a comprehensive resource of data to investigate the genetic variation of gene expression across a broad range of tissues and cell types. Recent studies have utilized the GTEx data to demonstrate that genetic correlation of gene expression between tissues in local regions (i.e., ±1Mb of the transcription start site) is much higher than that in distal regions14, consistent with the conclusions from the latest GTEx release13, and that there is no evidence for the tissue-relevant eQTLs being enriched for associations with complex traits15.
