Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin

Area of Science:

• Dermatology and Immunology
• Genetics and Genomics

Background:

• Psoriasis is a chronic inflammatory skin disease with poorly understood skin compartment changes.
• The role of the immune system in psoriasis is known, but skin-specific molecular alterations require further investigation.

Purpose of the Study:

• To identify expression quantitative trait loci (eQTLs) and their interactions with local skin inflammation in psoriasis.
• To explore the relationship between genetic variations, gene expression, and disease mechanisms in the skin compartment.

Main Methods:

• Analysis of longitudinal skin biopsies (n=375) from the PAUSE clinical trial (n=101).
• Identification and characterization of 953 eQTLs, with a focus on 116 eQTLs showing modulation by skin inflammation (eQTL interactions).

Main Results:

• Discovery of 953 eQTLs, including 116 eQTLs with inflammation-modulated effect sizes.
• Identification of eQTL genes (eGenes) predominantly expressed in skin, with a subset overlapping the NRF2 pathway.
• The strongest eQTL interaction (rs1491377616-LCE3C) connected a psoriasis risk locus to an epidermal gene.

Conclusions:

• This eQTL study provides novel insights into the genetic regulation of skin inflammation in psoriasis.
• The findings highlight the potential of using clinical trial biospecimens to uncover in vivo eQTL interactions relevant to therapeutic strategies.