Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

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 and Soumya Raychaudhuri ()
Additional contact information
Qian Xiao: Brigham and Women’s Hospital
Joseph Mears: Brigham and Women’s Hospital
Aparna Nathan: Brigham and Women’s Hospital
Kazuyoshi Ishigaki: Brigham and Women’s Hospital
Yuriy Baglaenko: Brigham and Women’s Hospital
Noha Lim: University of California, San Francisco
Laura A. Cooney: University of California, San Francisco
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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41984-2

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