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 replication set, 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 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 replication 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.

中文翻译：

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Paget骨疾病的表观遗传学分析可识别预测疾病状态的差异甲基化基因座

佩吉特氏骨病（PDB）的特征在于混乱的骨骼重塑的局灶性增加。这项研究旨在表征患者血液中PDB相关的DNA甲基化分布变化。来自发现和复制集的数据的荟萃分析包括116个PDB病例和130个对照，发现14个CpG位点，4个CpG岛和6个基因体区域的DNA甲基化存在显着差异。这些基因座，包括通过eQTM分析表征为功能性的两个基因座，与破骨细胞分化，机械负荷，免疫功能和病毒感染有关。发现基于发现样本的多元分类器可将PDB病例和对照与复制区分开，灵敏度为0.84，特异性为0.81，曲线下面积为92.8％。结论，