The GTEx Consortium has characterized genetic effects on gene expression across 44 human tissues, revealing that local genetic variation affects most genes, while 93 genes and 112 loci show inter-chromosomal effects. The study identifies tissue-specific gene expression patterns, local (cis-eQTLs) and distant (trans-eQTLs) effects, and evaluates the functional properties of genetic effects. Multi-tissue data enable identification of genes and pathways affected by disease-associated variation, providing insights into gene regulation and disease mechanisms. The GTEx project analyzed gene expression in 449 donors across 44 tissues, including 31 solid-organ tissues, 10 brain subregions, whole blood, and two cell lines. RNA sequencing was performed on 7,051 samples, with a median depth of 78 million reads. DNA was genotyped at 2.2 million sites and imputed to 12.5 million sites. The data provide the deepest survey of individual- and tissue-specific gene expression, enabling a comprehensive view of genetic variation's impact on gene expression. The study identified 152,869 cis-eQTLs for 19,725 genes, representing 50.3% and 86.1% of all known autosomal long intergenic noncoding RNA (lincRNA) and protein-coding genes. Trans-eQTLs were identified in 16 tissues, with 673 trans-eQTLs at a 10% genome-wide FDR. These include 112 distinct loci and 93 unique genes. The study also identified allele-specific expression (ASE) across tissues, with 63% of protein-coding genes tested for ASE in at least one donor and tissue. The study evaluated the sharing of eQTL effects across tissues, finding that cis-eQTLs are often shared across most tissues or specific to a small subset. Trans-eQTLs showed greater tissue specificity than cis-eQTLs. The study also characterized the functional properties of cis-eQTLs, finding that they are enriched in predicted promoter and enhancer states across 128 Roadmap Epigenomics project cell types. Cis-eQTLs were more likely to be shared across tissues when the eVariant overlaps the same chromatin state in both tissues. The study also characterized trans-eQTLs, finding that they are more enriched in enhancer regions than promoters. The study found that trans-eQTLs may be regulated by cis-eGenes, with the eVariant directly regulating expression of a nearby gene whose protein product then affects other genes downstream. The study also found that trans-eQTLs may be associated with protein function, false negatives in cis association tests, or unmeasured regulatory mechanisms. The study evaluated the replicability of cis-eQTLs, findingThe GTEx Consortium has characterized genetic effects on gene expression across 44 human tissues, revealing that local genetic variation affects most genes, while 93 genes and 112 loci show inter-chromosomal effects. The study identifies tissue-specific gene expression patterns, local (cis-eQTLs) and distant (trans-eQTLs) effects, and evaluates the functional properties of genetic effects. Multi-tissue data enable identification of genes and pathways affected by disease-associated variation, providing insights into gene regulation and disease mechanisms. The GTEx project analyzed gene expression in 449 donors across 44 tissues, including 31 solid-organ tissues, 10 brain subregions, whole blood, and two cell lines. RNA sequencing was performed on 7,051 samples, with a median depth of 78 million reads. DNA was genotyped at 2.2 million sites and imputed to 12.5 million sites. The data provide the deepest survey of individual- and tissue-specific gene expression, enabling a comprehensive view of genetic variation's impact on gene expression. The study identified 152,869 cis-eQTLs for 19,725 genes, representing 50.3% and 86.1% of all known autosomal long intergenic noncoding RNA (lincRNA) and protein-coding genes. Trans-eQTLs were identified in 16 tissues, with 673 trans-eQTLs at a 10% genome-wide FDR. These include 112 distinct loci and 93 unique genes. The study also identified allele-specific expression (ASE) across tissues, with 63% of protein-coding genes tested for ASE in at least one donor and tissue. The study evaluated the sharing of eQTL effects across tissues, finding that cis-eQTLs are often shared across most tissues or specific to a small subset. Trans-eQTLs showed greater tissue specificity than cis-eQTLs. The study also characterized the functional properties of cis-eQTLs, finding that they are enriched in predicted promoter and enhancer states across 128 Roadmap Epigenomics project cell types. Cis-eQTLs were more likely to be shared across tissues when the eVariant overlaps the same chromatin state in both tissues. The study also characterized trans-eQTLs, finding that they are more enriched in enhancer regions than promoters. The study found that trans-eQTLs may be regulated by cis-eGenes, with the eVariant directly regulating expression of a nearby gene whose protein product then affects other genes downstream. The study also found that trans-eQTLs may be associated with protein function, false negatives in cis association tests, or unmeasured regulatory mechanisms. The study evaluated the replicability of cis-eQTLs, finding