An epigenome-wide association study based on cell type-specific whole-genome bisulfite sequencing: Screening for DNA methylation signatures associated with bone mass

Shohei Komaki, Hideki Ohmomo, Tsuyoshi Hachiya, Ryohei Furukawa, Yuh Shiwa, Mamoru Satoh, Ryujin Endo, Minoru Doita, Makoto Sasaki, Atsushi Shimizu
2017 Integrative Molecular Medicine  
Bone mass can change intra-individually due to aging or environmental factors. Understanding the regulation of bone metabolism by epigenetic factors, such as DNA methylation, is essential to further our understanding of bone biology and facilitate the prevention of osteoporosis. To date, a single epigenome-wide association study (EWAS) of bone density has been reported, and our knowledge of epigenetic mechanisms in bone biology is strictly limited. Here, we conducted an EWAS based on cell
more » ... based on cell type-specific whole-genome bisulfite sequencing (WGBS) of CD3 + /CD4 + T cells and CD14 ++ /CD16monocytes collected from 102 Japanese individuals, and screened DNA methylation signatures associated with bone mass. Analyses based on each cell type revealed that distinct sets of DNA methylation signatures were associated with bone mass. Some genes annotated to those DNA methylation signatures have known cell type-specific roles in bone metabolism. The results of our comprehensive screening might also contain additional novel bone-related loci, which could further our understanding of the epigenetic mechanisms of bone metabolism. With few exceptions, the cell type-specific DNA methylation signatures identified in this study are not covered by widely used arrays. Our WGBS-based EWAS highlights the importance of cell type-specific analysis with broad genome coverage, especially for discovery phase.
doi:10.15761/imm.1000307 fatcat:xfcsj3ybqfbhrj7smy6i3hhf7a