Genomic modulators of gene expression in human neutrophils

Vivek Naranbhai (), Benjamin P. Fairfax (), Seiko Makino, Peter Humburg, Daniel Wong, Esther Ng, Adrian V. S. Hill and Julian C. Knight ()
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Vivek Naranbhai: Wellcome Trust Centre for Human Genetics, University of Oxford
Benjamin P. Fairfax: Wellcome Trust Centre for Human Genetics, University of Oxford
Seiko Makino: Wellcome Trust Centre for Human Genetics, University of Oxford
Peter Humburg: Wellcome Trust Centre for Human Genetics, University of Oxford
Daniel Wong: Wellcome Trust Centre for Human Genetics, University of Oxford
Esther Ng: Wellcome Trust Centre for Human Genetics, University of Oxford
Adrian V. S. Hill: Wellcome Trust Centre for Human Genetics, University of Oxford
Julian C. Knight: Wellcome Trust Centre for Human Genetics, University of Oxford

Nature Communications, 2015, vol. 6, issue 1, 1-13

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

Date: 2015
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DOI: 10.1038/ncomms8545

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