Whole genome DNA methylation profles defne Meniere’s disease subclusters Patil, Vibha Cruz-Granados, Pablo Cara, Francisca E. Amor-Dorado, Juan Carlos Aran, Ismael Soto-Varela, Andrés Pérez-Carpena, Patricia Lopez-Escamez, Jose Antonio WGBS Meniere’s disease T-cells Meniere disease (MD) is a cochleo-vestibular syndrome defned by episodes of vertigo associated with tinnitus and sensorineural hearing loss. While MD immune response has been linked to autoinfammation and type 2 cytokines, other molecular mechanisms such as DNA methylation have an emerging yet underexplored role in MD pathophysiology.To understand the role of DNA methylation in MD, we performed whole-genome bisulphite sequencing in MD patients (n=40) and controls (n=13) and used diferentially methylated cytosines (DMCs) to defne clusters, cell types, and biochemical pathways in MD. We found three MD subclusters: Cluster 1 (40% of patients) and Cluster 3 (25%) showed DMC profles against controls, while Cluster 2 (35%) did not. Signifcant DMCs from Cluster 1 and Cluster 3 versus Control analysis were annotated to 3033 and 59 unique genes, respectively. Each cluster showed a diferent gene enrichment; however, the KDMB4 gene had signifcant upregulated DNA accessibility in a complementary ATAC-seq dataset and showed signifcant DMCs in both Cluster 1 and Cluster 3. DNA methylation patterns in MD reveal three clusters which are refective of an underlying diference in pathways related to cytokine stimulus, immunity T-cell, and NK-cell pathways. KDMB4 emerges as a critical MD gene which deserves further research. 2025-09-15T10:51:53Z 2025-09-15T10:51:53Z 2025-08-06 journal article Patil, V., Cruz-Granados, P., Cara, F.E. et al. Whole genome DNA methylation profiles define Meniere’s disease subclusters. J Mol Med (2025). https://doi.org/10.1007/s00109-025-02581-6 https://hdl.handle.net/10481/106318 10.1007/s00109-025-02581-6 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Springer