Genetic effects on gene expression across human tissues

*Lists of authors and their affiliations appear at the end of the paper. A full list of Consortium members and their affiliations appears in the online version of the paper. The human genome encodes instructions for the regulation of gene expression, which varies both across cell types and across individuals. Recent large-scale studies have characterized the regulatory function of the genome across a diverse array of cell types, each from a small number of samples1–3. Measuring how gene regulation and expression vary across individuals has further expanded our understanding of the functions of healthy tissues and the molecular origins of complex traits and diseases4–9. However, these studies have been conducted in limited, accessible cell types, thus restricting the utility of these studies in informing regulatory biology and human health. The Genotype-Tissue Expression (GTEx) project was established to characterize human transcriptomes within and across individuals for a wide variety of primary tissues and cell types. Here, we report on a major expansion of the GTEx project that includes publicly available genotype, gene expression, histological and clinical data for 449 human donors across 44 (42 distinct) tissues. This enables the study of tissue-specific gene expression and the identification of genetic associations with gene expression levels (expression quantitative trait loci, or eQTLs) across many tissues, including both local (cis-eQTLs) and distal (trans-eQTLs) effects. In this study, we associate genetic variants with gene expression levels from the GTEx v6p release. We found pervasive cis-eQTLs, which affect the majority of human genes. In addition, we identify trans-eQTLs across 18 tissues and highlight their increased tissue specificity relative to cis-eQTLs. We evaluate both cisand trans-eQTLs with respect to their functional characteristics, genomic context, and relationship to disease-associated variation.

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