Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis

Deepti Verma, Anna-Karin Ekman, Cecilia Bivik Eding, Charlotta Enerbäck

Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls. We performed an exhaustive genome-wide DNA methylation profiling using reduced representation bisulfite sequencing, which interrogates the methylation status of ∼3-4 million CpG sites. More than two thousand strongly differentially methylated sites (DMS) were identified and a striking overrepresentation of the Wnt and cadherin pathways among the DMS was found. In particular, we observe a strong differential methylation in several psoriasis candidate genes. A substantial number of DMS present in the uninvolved vs healthy epidermis suggests the presence of a pre psoriatic state in the clinically healthy skin type. Our exploratory study represents a starting point for identifying biomarkers for psoriasis-prone skin before disease onset.