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

Abstract
Data availability
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Abstract

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

1. Albagha OM
2. Diboun I
3. Ralston SH
4. Wani S
(2020) Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status
NCBI Gene Expression Omnibus, GSE163970.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE163970

Article and author information

Author details

Ilhame Diboun

College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar

Competing interests
No competing interests declared.
Sachin Wani

Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, United Kingdom

Competing interests
No competing interests declared.
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..
Omar M E Albagha

College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar

For correspondence
oalbagha@hbku.edu.qa

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-5916-5983

Funding

European Research Council (FP7/2007-2013)

Ilhame Diboun

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.

Ethics

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.

Copyright

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.