1. Deconvolution of bulk blood eQTL effects into immune cell subpopulations
- Author
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Raúl Aguirre-Gamboa, Niek de Klein, Jennifer di Tommaso, Annique Claringbould, Monique GP van der Wijst, Dylan de Vries, Harm Brugge, Roy Oelen, Urmo Võsa, Maria M. Zorro, Xiaojin Chu, Olivier B. Bakker, Zuzanna Borek, Isis Ricaño-Ponce, Patrick Deelen, Cheng-Jiang Xu, Morris Swertz, Iris Jonkers, Sebo Withoff, Irma Joosten, Serena Sanna, Vinod Kumar, Hans J. P. M. Koenen, Leo A. B. Joosten, Mihai G. Netea, Cisca Wijmenga, BIOS Consortium, Lude Franke, and Yang Li more...
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eQTL ,Deconvolution ,Cell types ,Immune cells ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Expression quantitative trait loci (eQTL) studies are used to interpret the function of disease-associated genetic risk factors. To date, most eQTL analyses have been conducted in bulk tissues, such as whole blood and tissue biopsies, which are likely to mask the cell type-context of the eQTL regulatory effects. Although this context can be investigated by generating transcriptional profiles from purified cell subpopulations, current methods to do this are labor-intensive and expensive. We introduce a new method, Decon2, as a framework for estimating cell proportions using expression profiles from bulk blood samples (Decon-cell) followed by deconvolution of cell type eQTLs (Decon-eQTL). Results The estimated cell proportions from Decon-cell agree with experimental measurements across cohorts (R ≥ 0.77). Using Decon-cell, we could predict the proportions of 34 circulating cell types for 3194 samples from a population-based cohort. Next, we identified 16,362 whole-blood eQTLs and deconvoluted cell type interaction (CTi) eQTLs using the predicted cell proportions from Decon-cell. CTi eQTLs show excellent allelic directional concordance with eQTL (≥ 96–100%) and chromatin mark QTL (≥87–92%) studies that used either purified cell subpopulations or single-cell RNA-seq, outperforming the conventional interaction effect. Conclusions Decon2 provides a method to detect cell type interaction effects from bulk blood eQTLs that is useful for pinpointing the most relevant cell type for a given complex disease. Decon2 is available as an R package and Java application ( https://github.com/molgenis/systemsgenetics/tree/master/Decon2 ) and as a web tool ( www.molgenis.org/deconvolution ). more...
- Published
- 2020
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