Genomic modulators of gene expression in human neutrophils

• DOI: 10.1038/ncomms8545
• Publication Date: 2015-07-07T12:41:21Z
• Authors: Vivek Naranbhai; Benjamin P. Fairfax; Seiko Makino; Peter Humburg; Daniel Wong; Esther Ng; Adrian V. S. Hill; Julian C. Knight
• Keywords: Adult; Male; 0301 basic medicine; Genotype; Neutrophils; Quantitative Trait Loci; Genetic Variation; Genomics; Article; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Humans; Female

Abstract Neutrophils form the most abundant leukocyte subset and are central to many disease processes. Technical challenges in transcriptomic profiling have prohibited genomic approaches date. Here we map expression quantitative trait loci (eQTL) peripheral blood CD16+ neutrophils from 101 healthy European adults. We identify cis -eQTL for 3281 neutrophil-expressed genes including implicated neutrophil function, with 450 of these not previously observed myeloid or lymphoid cells. Paired comparison monocyte eQTL demonstrates nuanced conditioning genetic regulation gene by cellular context, which relates cell-type-specific DNA methylation histone modifications. Neutrophil markedly enriched trait-associated variants particularly autoimmune, allergy infectious disease. further demonstrate how PADI4 NOD2 delineate risk variant function rheumatoid arthritis, leprosy Crohn’s Taken together, data help advance understanding genetics expression, biology immune-related diseases.