Cell type specific genetic regulation of gene expression across human tissues

Sarah Kim-Hellmuth; 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 Brown; Angel 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

doi:10.1101/806117

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 Brown

Angel 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)

MED Population Health and Genomics

Research output: Working paper/Preprint › Preprint

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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 language	English
Publisher	BioRxiv
Number of pages	14
DOIs	https://doi.org/10.1101/806117
Publication status	Published - 17 Oct 2019

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10.1101/806117Licence: CC BY-NC-ND

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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.
Research output: Contribution to journal › Article › peer-review

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Kim-Hellmuth, S., Aguet, F., Oliva, M., Muñoz-Aguirre, M., Wucher, V., Kasela, S., 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., Zou, Y., Bonazzola, R., Quan, J., ... Lappalainen, T. (2019). Cell type specific genetic regulation of gene expression across human tissues. BioRxiv. https://doi.org/10.1101/806117

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title = "Cell type specific genetic regulation of gene expression across human tissues",

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.",

author = "Sarah Kim-Hellmuth and Fran{\c c}ois Aguet and Meritxell Oliva and Manuel Mu{\~n}oz-Aguirre and Valentin Wucher and Silva Kasela and Castel, \{Stephane E.\} and Hamel, \{Andrew R.\} and Ana Vi{\~n}uela and Roberts, \{Amy L.\} and Serghei Mangul and Xiaoquan Wen and Gao Wang and Barbeira, \{Alvaro N.\} and Diego Garrido-Mart{\'i}n and Brian Nadel and Yuxin Zou and Rodrigo Bonazzola and Jie Quan and Andrew Brown and Angel Martinez-Perez and Soria, \{Jos{\'e} Manuel\} and Gad Getz and Dermitzakis, \{Emmanouil T.\} and Small, \{Kerrin S.\} and Matthew Stephens and Xi, \{Hualin S.\} and Im, \{Hae Kyung\} and Roderic Guig{\'o} and Segr{\`e}, \{Ayellet V.\} and Stranger, \{Barbara E.\} and Ardlie, \{Kristin G.\} and Tuuli Lappalainen",

year = "2019",

month = oct,

day = "17",

doi = "10.1101/806117",

language = "English",

publisher = "BioRxiv",

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Kim-Hellmuth, S, Aguet, F, Oliva, M, Muñoz-Aguirre, M, Wucher, V, Kasela, S, Castel, SE, Hamel, AR, Viñuela, A, Roberts, AL, Mangul, S, Wen, X, Wang, G, Barbeira, AN, Garrido-Martín, D, Nadel, B, Zou, Y, Bonazzola, R, Quan, J, Brown, A, Martinez-Perez, A, Soria, JM, Getz, G, Dermitzakis, ET, Small, KS, Stephens, M, Xi, HS, Im, HK, Guigó, R, Segrè, AV, Stranger, BE, Ardlie, KG & Lappalainen, T 2019 'Cell type specific genetic regulation of gene expression across human tissues' BioRxiv. https://doi.org/10.1101/806117

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T1 - Cell type specific genetic regulation of gene expression across human tissues

AU - Kim-Hellmuth, Sarah

AU - Aguet, François

AU - Oliva, Meritxell

AU - Muñoz-Aguirre, Manuel

AU - Wucher, Valentin

AU - Kasela, Silva

AU - Castel, Stephane E.

AU - Hamel, Andrew R.

AU - Viñuela, Ana

AU - Roberts, Amy L.

AU - Mangul, Serghei

AU - Wen, Xiaoquan

AU - Wang, Gao

AU - Barbeira, Alvaro N.

AU - Garrido-Martín, Diego

AU - Nadel, Brian

AU - Zou, Yuxin

AU - Bonazzola, Rodrigo

AU - Quan, Jie

AU - Brown, Andrew

AU - Martinez-Perez, Angel

AU - Soria, José Manuel

AU - Getz, Gad

AU - Dermitzakis, Emmanouil T.

AU - Small, Kerrin S.

AU - Stephens, Matthew

AU - Xi, Hualin S.

AU - Im, Hae Kyung

AU - Guigó, Roderic

AU - Segrè, Ayellet V.

AU - Stranger, Barbara E.

AU - Ardlie, Kristin G.

AU - Lappalainen, Tuuli

PY - 2019/10/17

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N2 - 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.

AB - 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.

U2 - 10.1101/806117

DO - 10.1101/806117

M3 - Preprint

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

PB - BioRxiv

ER -

Cell type specific genetic regulation of gene expression across human tissues

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

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