Deconvolution of bulk blood eQTL effects into immune cell subpopulations

BMC Bioinformatics
Raul Aguirre-GamboaYang Li

Abstract

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). 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 subpopulat...Continue Reading

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Citations

Feb 12, 2021·European Journal of Immunology·Valerie A C M KoekenYang Li
Mar 24, 2021·BMC Bioinformatics·Fumihiko Takeuchi, Norihiro Kato
May 21, 2021·Scientific Reports·Zhenhua ZhangK Joeri van der Velde
Jun 12, 2021·Genomics·Jiao WangZhenxin Fan
Jun 29, 2021·Frontiers in Immunology·Xiaojing ChuYang Li
Mar 24, 2021·Cardiovascular Research·E L RobinsonUNKNOWN EU-CardioRNA COST Action CA17129

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Methods Mentioned

BETA
RNASeq
RNA-seq
FACS
scRNA-seq
biopsies
genotyping
flow cytometry

Software Mentioned

GENCODE
RS
Genotype Harmonizer
HTSeq
SAMTools
cell
NTR
R package
Decon2
cell R

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