Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

Abstract

Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.

Epigenetics: from the past to the present

“…Similar studies with remarkable findings in the investigation of a variety of diseases as type 2 diabetes mellitus (Soriano-Tarraga et al 2016), psoriasis (Zhou et al 2016), schizophrenia (Montano et al 2016), metabolic syndrome/obesity (Ali et al 2016) and many others have been recently published. It is expected that the new technologies that make possible this type of works and the technologies that will come allow epigenetic epidemiology to reach major objectives as the complete description of the epigenetic processes shaping the development of organisms, the interactions gene-epigene and epigene-environment, the establishment of the role of epigenetics in risk and emergence of diseases, as marker of disease or exposure, and the mechanisms of the inheritance of epigenetic changes over generations in humans (Bollati & Baccarelli 2010;Bakulski & Fallin 2014).…”

Epigenome-wide association data implicates DNA methylation-mediated genetic risk in psoriasis

“…Three types of tissues were collected, including 114 psoriatic skin tissues from psoriasis patients (PP), 41 matched uninvolved psoriatic skin tissues from psoriasis cases (PN), and 62 unaffected skin tissues from normal controls (NN). The detailed clinical characteristics and genome-wide methylation experiment had been described previously [7]. In this study, we only analyzed methylation data of 114 PP and 62 NN samples, the blood-derived genotype data from the same patients.…”

“…The methylation detection of each sample was described in detail in our previous study [7]. In brief, we performed single probe CPG methylation and psoriasis association by the non-parametric Wilcoxon rank-sum test.…”

“…Previously, we had identified 264 differentially methylated sites (DMSs) that were significantly associated with psoriasis [7]. However, the underlying mechanisms of how these methylation markers associated with psoriasis are not clear.…”

EWAS: epigenome-wide association studies software 1.0 – identifying the association between combinations of methylation levels and diseases

“…The epigenome-wide association studies aim to systematically identify epigenetic variants associated with complex diseases or phenotypes for case-control studies1415. So far, many complex diseases have been successfully analyzed by using the epigenome-wide association studies, such as Parkinson’s disease15, Schizophrenia16, Psoriasis17.…”