Dataset Information
Deconvolution of bulk blood eQTL effects into immune cell subpopulations.
Ontology highlight
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).
SUBMITTER: Aguirre-Gamboa R
PROVIDER: S-EPMC7291428 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Deconvolution of bulk blood eQTL effects into immune cell subpopulations.
BMC bioinformatics 20200612 1
<h4>Background</h4>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 ...[more]
