1. Chromosomes and Gene Expression
  2. Genetics and Genomics
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Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

  1. Ilhame Diboun
  2. Sachin Wani
  3. Stuart H Ralston
  4. Omar M E Albagha  Is a corresponding author
  1. Hamad Bin Khalifa University, Qatar
  2. University of Edinburgh, United Kingdom
Research Article
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Cite this article as: eLife 2021;10:e65715 doi: 10.7554/eLife.65715


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.

Data availability

Raw and processed methylation data generated in this study can be found at GEO under the accession GSE163970.

The following data sets were generated

Article and author information

Author details

  1. Ilhame Diboun

    College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
    Competing interests
    No competing interests declared.
  2. Sachin Wani

    Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  3. Stuart H Ralston

    Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    Stuart H Ralston, Prof S H Ralston has received research funding from Amgen, Eli Lilly, Novartis, and Pfizerunrelated to the submitted work. The author has no other competing interests to declare..
  4. Omar M E Albagha

    College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar
    For correspondence
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5916-5983


European Research Council (FP7/2007-2013)

  • Omar M E Albagha

European Research Council (787270-Paget-Advance)

  • 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.

Reviewing Editor

  1. Cheryl Ackert-Bicknell, University of Colorado, United States

Publication history

  1. Received: December 13, 2020
  2. Accepted: April 29, 2021
  3. Accepted Manuscript published: April 30, 2021 (version 1)
  4. Accepted Manuscript updated: May 4, 2021 (version 2)


© 2021, Diboun et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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