Whole genome DNA methylation profiles define Meniere's disease subclusters

Area of Science:

• Genomics and Epigenetics
• Otolaryngology
• Immunology

Background:

• Meniere disease (MD) is a complex cochleo-vestibular disorder.
• While immune responses are implicated, the role of DNA methylation in MD pathophysiology is underexplored.
• Understanding epigenetic mechanisms is crucial for novel therapeutic targets.

Purpose of the Study:

• To investigate the role of DNA methylation in Meniere disease.
• To identify distinct molecular subclusters within MD patients based on DNA methylation profiles.
• To explore potential key genes and pathways associated with MD pathophysiology.

Main Methods:

• Whole-genome bisulphite sequencing was performed on MD patients (n=40) and controls (n=13).
• Differentially methylated cytosines (DMCs) were used to define patient clusters and pathways.
• Complementary ATAC-seq data was utilized to assess DNA accessibility.

Main Results:

• Three distinct MD subclusters were identified based on DNA methylation patterns.
• Clusters 1 and 3 showed significant DMCs compared to controls, implicating 3033 and 59 genes, respectively.
• The KDMB4 gene exhibited significant DNA accessibility and DMCs in both affected clusters, suggesting a critical role.

Conclusions:

• DNA methylation patterns delineate distinct MD patient subclusters with unique molecular signatures.
• These patterns reflect underlying differences in cytokine stimulus, T-cell, and NK-cell pathways.
• KDMB4 is identified as a key gene warranting further investigation in Meniere disease.