ScienceGenomicsPeer-reviewed journal article
Cell type specific genetic regulation of gene expression across human tissues
Sarah Kim-HellmuthiD, François AguetiD, Meritxell OlivaiD, Manuel Muñoz-AguirreiD, Silva KaselaiD, Valentin WucheriD, Stephane E. CasteliD, Andrew R. HameliD, Ana ViñuelaiD, Amy L. RobertsiD, Serghei ManguliD, Xiaoquan WeniD, Gao T. WangiD, Alvaro BarbeiraiD, Diego Garrido-MartíniD, Brian B. NadeliD, Yuxin ZouiD, Rodrigo BonazzolaiD, Jie QuaniD, Andrew Anand BrowniD, Ángel Martínez-PéreziD, José Manuel SoriaiD, Gad A. GetziD, Emmanouil T. DermitzakisiD, Kerrin S. SmalliD, , Abhiram S. Rao
Abstract
The Genotype-Tissue Expression (GTEx) project has identified expression and splicing quantitative trait loci (cis-QTLs) for the majority of genes across a wide range of human tissues. However, the interpretation of these QTLs has been limited by the heterogeneous cellular composition of GTEx tissue samples. Here, we map 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 eQTLs provide finer resolution to tissue specificity than bulk tissue cis-eQTLs. Analyses of genetic associations to 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.\n\nOne Sentence SummaryEstimated cell type abundances from bulk RNA-seq across tissues reveal the cellular specificity of quantitative trait loci.
- organism: human
- assay: bulk RNA-seq
- research focus: gene regulatory network inference
- approach: statistical model
- Citations
- 550
- FWCI
- 58.25
- Field percentile
- top 1%
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