Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies

Tsuyoshi Hachiya, Ryohei Furukawa, Yuh Shiwa, Hideki Ohmomo, Kanako Ono, Fumiki Katsuoka, Masao Nagasaki, Jun Yasuda, Nobuo Fuse, Kengo Kinoshita, Masayuki Yamamoto, Kozo Tanno, Mamoru Satoh, Ryujin Endo, Makoto Sasaki, Kiyomi Sakata, Seiichiro Kobayashi, Kuniaki Ogasawara, Jiro Hitomi, Kenji SobueAtsushi Shimizu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Epigenome-wide association studies, which searches for blood-based DNA methylation signatures associated with environmental exposures and/or disease susceptibilities, is a promising approach to a better understanding of the molecular aetiology of common diseases. To carry out large-scale epigenome-wide association studies while avoiding false negative detection, an efficient strategy to determine target CpG sites for microarray-based or sequencing-based DNA methylation profiling is essentially needed. Here, we propose and validate a hypothesis that a strategy focusing on CpG sites with high DNA methylation level variability may attain an improved efficacy. Through whole-genome bisulfite sequencing of purified blood cells collected from > 100 apparently healthy subjects, we identified ~2.0 million inter-individually variable CpG sites as potential targets. The efficacy of our strategy was estimated to be 3.7-fold higher than that of the most frequently used strategy. Our catalogue of inter-individually variable CpG sites will accelerate the discovery of clinically relevant DNA methylation biomarkers in future epigenome-wide association studies.

Original languageEnglish
Article number0016
Journalnpj Genomic Medicine
Volume2
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies'. Together they form a unique fingerprint.

  • Cite this

    Hachiya, T., Furukawa, R., Shiwa, Y., Ohmomo, H., Ono, K., Katsuoka, F., Nagasaki, M., Yasuda, J., Fuse, N., Kinoshita, K., Yamamoto, M., Tanno, K., Satoh, M., Endo, R., Sasaki, M., Sakata, K., Kobayashi, S., Ogasawara, K., Hitomi, J., ... Shimizu, A. (2017). Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies. npj Genomic Medicine, 2(1), [0016]. https://doi.org/10.1038/s41525-017-0016-5