Cell type-specific genetic regulation of gene expression across human tissues.

Kim-Hellmuth, Sarah, François Aguet, Meritxell Oliva, Manuel Muñoz-Aguirre, Silva Kasela, Valentin Wucher, Stephane E Castel, et al. 2020. “Cell Type-Specific Genetic Regulation of Gene Expression across Human Tissues.”. Science (New York, N.Y.) 369 (6509).

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.

Last updated on 06/23/2023
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