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Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

Author

Listed:
  • Qian Xiao

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Joseph Mears

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Aparna Nathan

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Kazuyoshi Ishigaki

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Yuriy Baglaenko

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Noha Lim

    (University of California, San Francisco)

  • Laura A. Cooney

    (University of California, San Francisco
    University of Michigan)

  • Kristina M. Harris

    (University of California, San Francisco)

  • Mark S. Anderson

    (University of California, San Francisco)

  • David A. Fox

    (University of Michigan)

  • Dawn E. Smilek

    (University of California, San Francisco)

  • James G. Krueger

    (The Rockefeller University)

  • Soumya Raychaudhuri

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Brigham and Women’s Hospital and Harvard Medical School
    Broad Institute of MIT and Harvard)

Abstract

Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables.

Suggested Citation

  • Qian Xiao & Joseph Mears & Aparna Nathan & Kazuyoshi Ishigaki & Yuriy Baglaenko & Noha Lim & Laura A. Cooney & Kristina M. Harris & Mark S. Anderson & David A. Fox & Dawn E. Smilek & James G. Krueger , 2023. "Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41984-2
    DOI: 10.1038/s41467-023-41984-2
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    References listed on IDEAS

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