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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Vivek
authors.identifier: 0000000342818882
authors.initials: V
authors.lastname: Naranbhai
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Fairfax
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Seiko
authors.initials: S
authors.lastname: Makino
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Peter
authors.identifier: 0000000233316496
authors.initials: P
authors.lastname: Humburg
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wong
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Esther
authors.initials: E
authors.lastname: Ng
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Adrian V S
authors.identifier: 0000000309009629
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Knight
mesh_terms: D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D014644:Genetic Variation; D023281:Genomics / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D040641:Quantitative Trait Loci