@article{5c67d49591b84ec5900befd84bdefc34,
title = "Genomic modulators of gene expression in human neutrophils",
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.",
author = "Vivek Naranbhai and Fairfax, \{Benjamin P.\} and Seiko Makino and Peter Humburg and Daniel Wong and Esther Ng and Hill, \{Adrian V.S.\} and Knight, \{Julian C.\}",
note = "Funding Information: We thank the volunteers from the Oxford Biobank, NIHR Oxford Biomedical Research Centre, for their participation. The Oxford Biobank (www.oxfordbiobank.org.uk) is also part of the NIHR National Bioresource which supported the recalling process of the volunteers. This work was supported by the Wellcome Trust (Grants 074318 (J.C.K.), 088891 (B.P.F.), and 090532/Z/09/Z (core facilities Wellcome Trust Centre for Human Genetics including High-Throughput Genomics Group)), the European Research Council under the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007–2013)/ ERC Grant agreement no. 281824 (J.C.K.), the Medical Research Council (98082 (J.C.K)) and the NIHR Oxford Biomedical Research Centre. V.N. was supported by the Rhodes Trust. We thank the volunteers for their participation in this study, Sr Jane Cheeseman for assistance in enrolling participants, Dr Katharine Plant for administrative assistance during the conduct of this study and Dr Christina Chang for help with illustrations. We also thank Prof{\textquoteright}s Yuta Kochi, Alison Simmons, Dr{\textquoteright}s Yukinori Okada and Luke Jostins and Mr Daniel Gaughan for helpful discussions. Publisher Copyright: {\textcopyright} 2015, Nature Publishing Group. All rights reserved.",
year = "2015",
month = jul,
day = "7",
doi = "10.1038/ncomms8545",
language = "English",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
