Longitudinal DNA methylation dynamics as a practical indicator in clinical epigenetics

Shohei Komaki; Hideki Ohmomo; Tsuyoshi Hachiya; Yoichi Sutoh; Kanako Ono; Ryohei Furukawa; So Umekage; Yayoi Otsuka-Yamasaki; Kozo Tanno; Makoto Sasaki; Atsushi Shimizu

doi:10.1186/s13148-021-01202-6

Longitudinal DNA methylation dynamics as a practical indicator in clinical epigenetics

Clin Epigenetics. 2021 Dec 13;13(1):219. doi: 10.1186/s13148-021-01202-6.

Authors

Shohei Komaki¹, Hideki Ohmomo¹, Tsuyoshi Hachiya¹, Yoichi Sutoh¹, Kanako Ono¹, Ryohei Furukawa^{1

2}, So Umekage¹, Yayoi Otsuka-Yamasaki¹, Kozo Tanno^{3

4}, Makoto Sasaki^{5

6}, Atsushi Shimizu^{7

8}

Affiliations

¹ 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.
² Department of Biology, Research and Education Center for Natural Sciences, Keio University, 4-1-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8521, Japan.
³ Division of Clinical Research and Epidemiology, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
⁴ Department of Hygiene and Preventive Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba, Shiwa, Iwate, 028-3694, Japan.
⁵ Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.
⁶ Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, 1-1-1 Idaidori, Yahaba, Shiwa, Iwate, 028-3694, Japan.
⁷ 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. ashimizu@iwate-med.ac.jp.
⁸ Division of Biomedical Information Analysis, Institute for Biomedical Sciences, Iwate Medical University, 1-1-1 Idaidori, Yahaba, Shiwa, Iwate, 028-3694, Japan. ashimizu@iwate-med.ac.jp.

Abstract

Background: 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.

Results: 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.

Conclusions: 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.

Keywords: Blood DNA methylation; EWAS marker likelihood; Illumina 450 K beadchip; Temporal stability.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation / genetics*
Epigenomics / methods*
Epigenomics / standards
Humans