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

ABSTRACT: Epigenetic analysis of Paget’s disease of bone identifies differentially methylated loci that predict disease status

PROVIDER: PRJNA688467 | ENA |

REPOSITORIES: ENA

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

Project description:This study demonstrated that PDB has an epigenetic signature in the blood and that differentially methylated sites in white blood cells may be used as predictive markers of the disease. Many of the identified changes in DNA methylation were associated with genes that regulate osteoclast function, immune responses, host reponse to viral infection, pain pathways and pathways involved in mechanosensing.

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

Project description: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.

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