Christofidou Paraskevi, Bell Christopher G
William Harvey Research Institute, Barts & The London Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
QMUL Centre for Epigenetics, Queen Mary University of London, London, UK.
Epigenomics. 2025 Jun;17(9):599-610. doi: 10.1080/17501911.2025.2500907. Epub 2025 May 10.
Early and accurate diagnosis significantly improves the chances of disease survival. DNA methylation (5mC), the major DNA modification in the human genome, is now recognized as a biomarker of immense clinical potential. This is due to its ability to delineate precisely cell-type, quantitate both internal and external exposures, as well as tracking chronological and biological components of the aging process. Here, we survey the current state of DNA methylation as a biomarker and predictor of traits and disease. This includes Epigenome-wide association study (EWAS) findings that inform Methylation Risk Scores (MRS), EpiScore long-term estimators of plasma protein levels, and machine learning (ML) derived DNA methylation clocks. These all highlight the significant benefits of accessible peripheral blood DNA methylation as a surrogate measure. However, detailed DNA methylation biopsy analysis in real-time is also empowering pathological diagnosis. Furthermore, moving forward, in this multi-omic and biobank scale era, novel insights will be enabled by the amplified power of increasing sample sizes and data integration.
早期准确诊断可显著提高疾病存活几率。DNA甲基化（5mC）是人类基因组中的主要DNA修饰，现已被视为具有巨大临床潜力的生物标志物。这是因为它能够精确描绘细胞类型、定量内部和外部暴露，以及追踪衰老过程的时间和生物学成分。在此，我们综述了DNA甲基化作为性状和疾病生物标志物及预测指标的现状。这包括全表观基因组关联研究（EWAS）的结果，这些结果为甲基化风险评分（MRS）、血浆蛋白水平的长期表观遗传评分估计值以及机器学习（ML）衍生的DNA甲基化时钟提供了信息。这些都突出了可获取的外周血DNA甲基化作为替代指标的显著优势。然而，实时详细的DNA甲基化活检分析也有助于病理诊断。此外，展望未来，在这个多组学和生物样本库规模的时代，样本量增加和数据整合的强大力量将带来新的见解。
