Cell type specific genetic regulation of gene expression across human tissues

Sarah Kim-Hellmuth (Lead / Corresponding author), François Aguet, Meritxell Oliva, Manuel Muñoz-Aguirre, Valentin Wucher, Silva Kasela, Stephane E. Castel, Andrew R. Hamel, Ana Viñuela, Amy L. Roberts, Serghei Mangul, Xiaoquan Wen, Gao Wang, Alvaro N. Barbeira, Diego Garrido-Martín, Brian Nadel, Yuxin Zou, Rodrigo Bonazzola, Jie Quan, Andrew BrownAngel Martinez-Perez, José Manuel Soria, Gad Getz, Emmanouil T. Dermitzakis, Kerrin S. Small, Matthew Stephens, Hualin S. Xi, Hae Kyung Im, Roderic Guigó, Ayellet V. Segrè, Barbara E. Stranger, Kristin G. Ardlie, Tuuli Lappalainen (Lead / Corresponding author)

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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.
One Sentence Summary Estimated cell type abundances from bulk RNA-seq across tissues reveal the cellular specificity of quantitative trait loci.
Original languageEnglish
PublisherBioRxiv
Number of pages14
DOIs
Publication statusPublished - 17 Oct 2019

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

    Kim-Hellmuth, S. (Lead / Corresponding author), Aguet, F., Oliva, M., Muñoz-Aguirre, M., Kasela, S., Wucher, V., Castel, S. E., Hamel, A. R., Viñuela, A., Roberts, A. L., Mangul, S., Wen, X., Wang, G., Barbeira, A. N., Garrido-Martín, D., Nadel, B. B., Zou, Y., Bonazzola, R., Quan, J. & Brown, A. & 14 others, Martinez-Perez, A., Soria, J. M., GTEx Consortium, Getz, G., Dermitzakis, E. T., Small, K. S., Stephens, M., Xi, H. S., Im, H. K., Guigó, R., Segrè, A. V., Stranger, B. E., Ardlie, K. G. & Lappalainen, T. (Lead / Corresponding author), 11 Sept 2020, In: Science (New York, N.Y.). 369, 6509, 11 p., eaaz8528.

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