DNA methylation changes in infants between 6 and 52 weeks

Ellen Wikenius,Einar R Heiervang,Anders Berglund,Vibeke Moe,Lars Smith

doi:10.1038/s41598-019-54355-z

Abstract

Infants undergo extensive developments during their first year of life. Although the biological mechanisms involved are not yet fully understood, changes in the DNA methylation in mammals are believed to play a key role. This study was designed to investigate changes in infant DNA methylation that occurs between 6 and 52 weeks. A total of 214 infant saliva samples from 6 or 52 weeks were assessed using principal component analyses and t-distributed stochastic neighbor-embedding algorithms. Between the two time points, there were clear differences in DNA methylation. To further investigate these findings, paired two-sided student’s t-tests were performed. Differently methylated regions were defined as at least two consecutive probes that showed significant differences, with a q-value < 0.01 and a mean difference > 0.2. After correcting for false discovery rates, changes in the DNA methylation levels were found in 42 genes. Of these, 36 genes showed increased and six decreased DNA methylation. The overall DNA methylation changes indicated decreased gene expression. This was surprising because infants undergo such profound developments during their first year of life. The results were evaluated by taking into consideration the extensive development that occurs during pregnancy. During the first year of life, infants have an overall three-fold increase in weight, while the fetus develops from a single cell into a viable infant in 9 months, with an 875-million-fold increase in weight. It is possible that the findings represent a biological slowing mechanism in response to extensive fetal development. In conclusion, our study provides evidence of DNA methylation changes during the first year of life, representing a possible biological slowing mechanism. We encourage future studies of DNA methylation changes in infants to replicate the findings by using a repeated measures model and less stringent criteria to see if the same genes can be found, as well as investigating whether other genes are involved in development during this period.

Highlights

Infants undergo extensive developments during their first year of life
The results showed platelet epithelial cells and bacteria, no immune cells, but as this was only a performed at 6 weeks on a small sample, leucocytes in the samples could not be excluded, the amount of leukocytes in all saliva samples was calculated using the leukocytes methylation for purity (LUMP) analysis[23]; the results showed that 42 of the 256 samples contained > 10% leukocytes
The greatest consistent difference is the time point and nonindividual differences. Because both the principal component analyses (PCA) and t-distributed stochastic neighbor embedding (t-SNE) showed the same separation in infant DNA methylation between the two time points, the findings indicate that the biological mechanisms associated with normal infant development in the first year of life are associated with DNA methylation changes

Summary

Introduction

Infants undergo extensive developments during their first year of life. the biological mechanisms involved are not yet fully understood, changes in the DNA methylation in mammals are believed to play a key role. This study was designed to investigate changes in infant DNA methylation that occurs between 6 and 52 weeks. The overall DNA methylation changes indicated decreased gene expression. This was surprising because infants undergo such profound developments during their first year of life. Our study provides evidence of DNA methylation changes during the first year of life, representing a possible biological slowing mechanism. We encourage future studies of DNA methylation changes in infants to replicate the findings by using a repeated measures model and less stringent criteria to see if the same genes can be found, as well as investigating whether other genes are involved in development during this period. Epigenetic drift relates to the changes in DNA methylation over time, which differs among individuals[11]. It is thought that the promoter regions initiate the transcription of a particular gene[16], and it is widely recognized that the DNA methylation of this area is associated with decreased gene expression[17]

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