Individual variation and longitudinal pattern of genome-wide DNA methylation from birth to the first two years of life

Abstract

Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5′UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3′UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.

Keywords: :

• CpG
• DIP test
• DNA Methylation
• empirical bayes
• genome-wide
• normal mixture

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The parent study is supported in part by the March of Dimes PERI grants (PI: Wang, 20-FY02–56), the NIEHS (PI: Wang, R21 ES011666), and the NICHD (PI: Wang, R01 HD041702). The study is supported in part by the Food Allergy Initiative, the March of Dimes Birth Defects Foundation (PI: Tsai, 21-FY07-605) the NIAID (PI: Wang, R21AI079872; R21AI088609; U01AI090727), and the NICHD (PI: Wang, R21HD066471). This study also is supported in part by the Department of Defense (PI: Wang, W81XWH-10–1-0123). Dr. Liu is supported by the NIAID (PI: Liu, R21AI087888). None of the authors have a conflict of interest pertaining to this work.

Author Contributions

Designed the study and provided direction: XW XL DW. Conducted data analyses and interpretation of results: DW XL HX YZ XW. Performed the lab analysis: XH GW RL. Draft and revision of the manuscript: DW XL HX HJT XH GW RL XW. Provided financial support: XW XL HJT.