Cell type specific genetic regulation of gene expression across human tissues

作者：Sarah Kim-Hellmuth, F. Aguet, Meritxell Oliva, Manuel Muñoz-Aguirre, S. Kasela, Valentin Wucher, S. Castel, A. Hamel, A. Viñuela, A. Roberts, S. Mangul, X. Wen, Gao Wang, A. Barbeira, D. Garrido-Martín, B. Nadel, Yu-Xin Zou, Rodrigo Bonazzola, J. Quan, A. Brown, A. Martinez-Perez, J. Soria, G. Getz, E. Dermitzakis, K. Small, M. Stephens, H. Xi, H. Im, R. Guigó, A. Segrè, B. Stranger, K. Ardlie, T. Lappalainen · 发表于：Science · 年份：2019 · DOI：10.1126/science.aaz8528 · 被引用次数：336 · 研究领域：Biology、Medicine

Cell type composition, estimated from bulk tissue, maps the cellular specificity of genetic variants. Cell type–specific quantitative trait loci Understanding how human genetic variation affects phenotype requires tissue- or even cell type–specific measurements. Kim-Hellmuth et al. used computational methods to identify cell-type proportions within bulk tissues in the Genotype-Tissue Expression (GTEx) project dataset to identify cell-type interaction quantitative trait loci and map these to genetic variants correlated with expression or splicing differences between individuals. By characterizing the cellular context, this study illustrates how genetic variants that operate in a cell type–specific manner affect gene regulation and can be linked to complex traits. This deconvolution and analysis of cell types from bulk tissues allows greater precision in understanding how phenotypes are linked to genetic variation. Science, this issue p. eaaz8528 INTRODUCTION Efforts to map quantitative trait loci (QTLs) across human tissues by the GTEx Consortium and others have identified expression and splicing QTLs (eQTLs and sQTLs, respectively) for a majority of genes. However, these studies were largely performed with gene expression measurements from bulk tissue samples, thus obscuring the cellular specificity of genetic regulatory effects and in turn limiting their functional interpretation. Identifying the cell type (or types) in which a QTL is active will be key to uncovering the mol...