Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, 1-1-1, Idaidori, Yahaba, Iwate, 028-3694, Japan.
Department of Biology, Research and Education Center for Natural Sciences, Keio University, 4-1-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8521, Japan.
Clin Epigenetics. 2021 Dec 13;13(1):219. doi: 10.1186/s13148-021-01202-6.
One of the fundamental assumptions of DNA methylation in clinical epigenetics is that DNA methylation status can change over time with or without interplay with environmental and clinical conditions. However, little is known about how DNA methylation status changes over time under ordinary environmental and clinical conditions. In this study, we revisited the high frequency longitudinal DNA methylation data of two Japanese males (24 time-points within three months) and characterized the longitudinal dynamics.
The results showed that the majority of CpGs on Illumina HumanMethylation450 BeadChip probe set were longitudinally stable over the time period of three months. Focusing on dynamic and stable CpGs extracted from datasets, dynamic CpGs were more likely to be reported as epigenome-wide association study (EWAS) markers of various traits, especially those of immune- and inflammatory-related traits; meanwhile, the stable CpGs were enriched in metabolism-related genes and were less likely to be EWAS markers, indicating that the stable CpGs are stable both in the short-term within individuals and under various environmental and clinical conditions.
This study indicates that CpGs with different stabilities are involved in different functions and traits, and thus, they are potential indicators that can be applied for clinical epigenetic studies to outline underlying mechanisms.
临床表观遗传学中 DNA 甲基化的一个基本假设是，DNA 甲基化状态可以随着时间的推移而变化，无论是否与环境和临床条件相互作用。然而，人们对普通环境和临床条件下 DNA 甲基化状态随时间的变化知之甚少。在这项研究中，我们重新分析了两名日本男性（三个月内 24 个时间点）的高频纵向 DNA 甲基化数据，并对其进行了纵向动力学特征分析。
结果表明，在三个月的时间内，Illumina HumanMethylation450 BeadChip 探针集上的大多数 CpG 在纵向是稳定的。关注从数据集提取的动态和稳定 CpG，动态 CpG 更有可能被报道为各种特征的全基因组关联研究（EWAS）标记物，尤其是与免疫和炎症相关的特征；同时，稳定的 CpG 富集在代谢相关基因中，不太可能成为 EWAS 标记物，这表明稳定的 CpG 在个体的短期和各种环境和临床条件下都是稳定的。
这项研究表明，具有不同稳定性的 CpG 参与不同的功能和特征，因此，它们是潜在的指标，可以应用于临床表观遗传学研究，以描绘潜在的机制。
