Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Paget's disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients' blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease.

Automated summary

The study aimed to characterize changes in DNA methylation profiles in the blood of Paget's disease of bone (PDB) patients, identifying significant differences in DNA methylation at certain loci associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on the data was able to discriminate PDB cases and controls with high sensitivity, specificity, and accuracy, indicating that epigenetic factors play a role in the pathogenesis of PDB and may serve as diagnostic markers for predicting the disease.