细胞类型特异性基因表达的遗传调控跨越人体组织。
Cell type-specific genetic regulation of gene expression across human tissues.
机构信息
Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
New York Genome Center, New York, NY, USA.
出版信息
Science. 2020 Sep 11;369(6509). doi: 10.1126/science.aaz8528.
Abstract
The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci in cis (QTLs) for the majority of genes across a wide range of human tissues. However, the functional characterization of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. We mapped interactions between computational estimates of cell type abundance and genotype to identify cell type-interaction QTLs for seven cell types and show that cell type-interaction expression QTLs (eQTLs) provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations with 87 complex traits show a contribution from cell type-interaction QTLs and enables the discovery of hundreds of previously unidentified colocalized loci that are masked in bulk tissue.
摘要
基因型组织表达 (GTEx) 项目已确定了广泛的人类组织中顺式（QTLs）的表达和剪接数量性状基因座。然而，这些 QTL 的功能特征受到 GTEx 组织样本中异质细胞组成的限制。我们将计算估计的细胞类型丰度与基因型之间的相互作用进行映射，以鉴定七种细胞类型的细胞类型相互作用 QTL，并表明细胞类型相互作用表达 QTL（eQTLs）比批量组织 cis-eQTL 提供更精细的组织特异性分辨率。对 87 个复杂性状的遗传关联分析显示，细胞类型相互作用 QTL 有一定的贡献，并能够发现数百个以前未被识别的、在批量组织中被掩盖的共定位基因座。
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