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Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity

Author

Listed:
  • James J. Gilchrist

    (University of Oxford
    University of Oxford
    University of Oxford)

  • Seiko Makino

    (University of Oxford)

  • Vivek Naranbhai

    (University of Oxford)

  • Piyush K. Sharma

    (University of Oxford
    University of Oxford)

  • Surya Koturan

    (University of Oxford
    University of Oxford)

  • Orion Tong

    (University of Oxford
    University of Oxford)

  • Chelsea A. Taylor

    (University of Oxford
    University of Oxford)

  • Robert A. Watson

    (University of Oxford
    University of Oxford)

  • Alba Verge los Aires

    (University of Oxford
    University of Oxford)

  • Rosalin Cooper

    (University of Oxford
    University of Oxford)

  • Evelyn Lau

    (University of Oxford)

  • Sara Danielli

    (University of Oxford)

  • Dan Hameiri-Bowen

    (University of Oxford)

  • Wanseon Lee

    (University of Oxford)

  • Esther Ng

    (University of Oxford)

  • Justin Whalley

    (University of Oxford)

  • Julian C. Knight

    (University of Oxford
    University of Oxford)

  • Benjamin P. Fairfax

    (University of Oxford
    University of Oxford
    Oxford University Hospitals NHS Foundation Trust)

Abstract

Natural Killer cells are innate lymphocytes with central roles in immunosurveillance and are implicated in autoimmune pathogenesis. The degree to which regulatory variants affect Natural Killer cell gene expression is poorly understood. Here we perform expression quantitative trait locus mapping of negatively selected Natural Killer cells from a population of healthy Europeans (n = 245). We find a significant subset of genes demonstrate expression quantitative trait loci specific to Natural Killer cells and these are highly informative of human disease, in particular autoimmunity. A Natural Killer cell transcriptome-wide association study across five common autoimmune diseases identifies further novel associations at 27 genes. In addition to these cis observations, we find novel master-regulatory regions impacting expression of trans gene networks at regions including 19q13.4, the Killer cell Immunoglobulin-like Receptor region, GNLY, MC1R and UVSSA. Our findings provide new insights into the unique biology of Natural Killer cells, demonstrating markedly different expression quantitative trait loci from other immune cells, with implications for disease mechanisms.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31626-4
    DOI: 10.1038/s41467-022-31626-4
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