Battle Alexis, Brown Christopher D, Engelhardt Barbara E, Montgomery Stephen B
Department of Computer Science, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Nature. 2017 Oct 11;550(7675):204-213. doi: 10.1038/nature24277.
Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.
表征人类基因组的分子功能及其个体间的变异，对于确定构成人类遗传性状和疾病基础的细胞机制至关重要。基因型-组织表达（GTEx）项目旨在表征人体不同个体和多种组织中基因表达水平的变异，其中许多组织不易获取。在此，我们描述了对44种人体组织中基因表达水平的遗传效应。我们发现，局部遗传变异影响大多数基因的表达水平，并且进一步鉴定出93个基因和112个位点的染色体间遗传效应。基于所鉴定的遗传效应，我们表征了组织特异性模式，比较了局部和远端效应，并评估了遗传效应的功能特性。我们还证明，多组织、多个体数据可用于识别受人类疾病相关变异影响的基因和通路，从而对基因调控和疾病的遗传基础进行机制性解释。
