Abstract
BACKGROUND: Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory and neurodegenerative traits. Recently, DNA methylation has emerged as a promising field of investigation for elucidating dynamics characterizing MS development and progression. OBJECTIVES: This study aimed to comprehensively investigate the role of epigenetics in MS by analyzing the methylation profiles from blood and brain tissues from public datasets. METHODS: Employing a meta-analytical framework for differential methylation analyses, the study extended beyond conventional analyses to explore additional dimensions of epigenetic regulation, including epigenetic drift, age acceleration, and rare epivariations. RESULTS: Results of the differential methylation analysis were in line with previously reported findings. No significant differences were observed in age acceleration or global epigenetic drift between MS cases and controls. However, upon closer analysis at the gene level, distinctive patterns of epigenetic drift emerged, particularly within genes implicated in neural biological functions. CONCLUSIONS: These findings underscore the role of epigenetic modifications in shaping MS pathology. Furthermore, the study unveiled the exclusive presence of rare epivariations within the MS cases, some of which involved genes previously linked to MS or other autoimmune diseases. This highlights the potential significance of rare genetic aberrations in driving MS susceptibility and progression.