Genome-Wide DNA Methylation Profiling Reveals Low Methylation Variability in Moyamoya Disease

Area of Science:

• Epigenetics
• Cerebrovascular Biology
• Genomics

Background:

• Moyamoya disease (MMD) is a chronic cerebrovascular disorder associated with stroke risk.
• Gene-environment interactions are implicated in MMD pathogenesis.
• Epigenetic modifications, specifically DNA methylation, are largely unexplored in MMD.

Purpose of the Study:

• To investigate genome-wide DNA methylation patterns in MMD.
• To compare methylation variability between MMD patients and healthy controls across diverse cohorts.
• To identify biological pathways affected by altered DNA methylation in MMD.

Main Methods:

• Genome-wide DNA methylation analysis using Illumina 850K Methylation EPIC BeadChip.
• Study included two racially distinct adult female cohorts and an external validation cohort of both sexes.
• Differential methylation variability analysis between MMD patients and controls.

Main Results:

• Strikingly low DNA methylation variability observed in MMD patients compared to healthy controls in both female cohorts.
• Reduced methylation variability was confirmed across 2845 probes in the Asian cohort.
• Differentially variable probes were enriched in genes regulating methylation, transcription, DNA repair, and cellular processes.

Conclusions:

• This study reports the first observation of reduced DNA methylation variability in any disease, specifically in Moyamoya disease.
• This epigenetic characteristic may compromise MMD patients' ability to adapt to environmental stressors, impacting vascular homeostasis.
• Findings provide novel insights into MMD mechanisms and potential therapeutic targets.