Science. 2020 Sep 11;369(6509):1318-1330. doi: 10.1126/science.aaz1776.
The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the version 8 data, examining 15,201 RNA-sequencing samples from 49 tissues of 838 postmortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue specificity of genetic effects and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.
基因型组织表达（GTEx）项目旨在描述人类组织中转录组的遗传效应，并将这些调控机制与性状和疾病关联联系起来。在这里，我们分析了版本 8 的数据，研究了 838 位死后捐献者的 49 种组织中的 15201 个 RNA 测序样本。我们全面描述了顺式和反式转录组中基因表达和剪接的遗传关联，表明几乎所有基因都存在调控关联，并描述了潜在的分子机制及其对复杂性状等位基因异质性和多效性的贡献。利用组织多样性的优势，我们深入了解遗传效应的组织特异性，并表明细胞类型组成是理解人类组织中基因调控机制的关键因素。
