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

eLife

Sachin Wani¹  Stuart H Ralston¹  Ilhame Diboun²  Omar ME Albagha³ 

[1] Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;Division of Genomic and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar;Division of Genomic and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar;Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;

关键词: paget's disease;    epigenetics;    bone;    Human;   

DOI  :  10.7554/eLife.65715

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY