Cell Specific eQTL Analysis without Sorting Cells

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn’s disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.Author Summary: Many variants in the genome, including variants associated with disease, affect the expression of genes. These so-called expression quantitative trait loci (eQTL) can be used to gain insight in the downstream consequences of disease. While it has been shown that many disease-associated variants alter gene expression in a cell-type dependent manner, eQTL datasets for specific cell types may not always be available and their sample size is often limited. We present a method that is able to detect cell type specific effects within eQTL datasets that have been generated from whole tissues (which may be composed of many cell types), in our case whole blood. By combining numerous whole blood datasets through meta-analysis, we show that we are able to detect eQTL effects that are specific for neutrophils and lymphocytes (two blood cell types). Additionally, we show that the variants associated with some diseases may preferentially alter the gene expression in one of these cell types. We conclude that our method is an alternative method to detect cell type specific eQTL effects, that may complement generating cell type specific eQTL datasets and that may be applied on other cell types and tissues as well.