TY - JOUR
T1 - Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin
AU - Xiao, Qian
AU - Mears, Joseph
AU - Nathan, Aparna
AU - Ishigaki, Kazuyoshi
AU - Baglaenko, Yuriy
AU - Lim, Noha
AU - Cooney, Laura A.
AU - Harris, Kristina M.
AU - Anderson, Mark S.
AU - Fox, David A.
AU - Smilek, Dawn E.
AU - Krueger, James G.
AU - Raychaudhuri, Soumya
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-41984-2
DO - 10.1038/s41467-023-41984-2
M3 - Article
C2 - 37805522
AN - SCOPUS:85173981521
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 6268
ER -