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Chunk #3 — RESULTS — Defining eQTLs in purified B-cell and monocyte populations

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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.
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B-cells are lymphocytes with crucial roles in adaptive and humoral immunity whilst monocytes form an innate myeloid derived cell population that initiates an inflammatory, cytokine mediated response upon microorganism invasion. Their divergent functions and origins ensure these cell populations form highly informative primary tissue for insight into immune and inflammatory diseases. Furthermore, whereas multiple LCL eQTL analyses have been performed, as yet there are no large studies focused on B-cells, the cells immortalized to derive LCLs. To investigate eQTLs in these primary cell types we used positive selection, a method demonstrated to result in superior cell purity for microarray analysis13 to separate CD19+ B-cells and CD14+ monocytes from PBMCs prepared using the whole blood of 288 healthy European volunteers (Online methods). Purity of samples was confirmed with flow cytometry and was 90-95% for B-cells and approaching 99% for monocytes. Genome-wide gene expression profiling and genotyping was performed using HumanHT-12 v4 BeadChips (Illumina) and HumanOmniExpress-12v1.0 BeadChips (Illumina). Following processing and quality control we performed eQTL mapping at 651210 markers for each of 283 individuals.