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Genomic modulators of gene expression in human neutrophils

Author

Listed:
  • 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)

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.

Suggested Citation

  • Vivek Naranbhai & Benjamin P. Fairfax & Seiko Makino & Peter Humburg & Daniel Wong & Esther Ng & Adrian V. S. Hill & Julian C. Knight, 2015. "Genomic modulators of gene expression in human neutrophils," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8545
    DOI: 10.1038/ncomms8545
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    Cited by:

    1. Ashley Budu-Aggrey & Anna Kilanowski & Maria K. Sobczyk & Suyash S. Shringarpure & Ruth Mitchell & Kadri Reis & Anu Reigo & Reedik Mägi & Mari Nelis & Nao Tanaka & Ben M. Brumpton & Laurent F. Thomas , 2023. "European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. James J. Gilchrist & Seiko Makino & Vivek Naranbhai & Piyush K. Sharma & Surya Koturan & Orion Tong & Chelsea A. Taylor & Robert A. Watson & Alba Verge los Aires & Rosalin Cooper & Evelyn Lau & Sara D, 2022. "Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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