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 of 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 (eQTM) 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.
Raw and processed methylation data generated in this study can be found at GEO under the accession GSE163970.
Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease statusNCBI Gene Expression Omnibus, GSE163970.
- Omar M E Albagha
- Stuart H Ralston
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The study was approved by the UK Multicenter Research Ethics Committee for Scotland(MREC01/0/53) and NHS Lothian, Edinburgh (08/S1104/8) ethics review committees. Allparticipants provided written informed consent.
- Cheryl Ackert-Bicknell, University of Colorado, United States
© 2021, Diboun et al.
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