The role of DNA methylation in gestational age

Abstract

Epigenetic modifications, such as DNA methylation, are implicated in a wide array of developmental processes, including cellular differentiation and human development. The overarching aim of this thesis was to explore genome-wide DNA methylation levels in newborns in relation to their gestational age and identify mechanisms that might explain this association. Cord blood DNA methylation levels in several subsamples from the Norwegian Mother, Father, and Child Cohort Study were quantified using DNA methylation microarrays. Different statistical methods and approaches were used to shed light on the association between DNA methylation and gestational age. Most of the DNA methylation markers (CpGs) that correlated with gestational age were associated with genes involved in the development of red blood cells. The findings also pointed to genes related to various developmental processes, as well as preparation for birth and life outside the womb. Furthermore, a DNA methylation-based model to accurately predict gestational age, referred to as an "epigenetic clock" for gestational age, was developed. The clock worked equally well for newborns conceived with and without the aid of assisted reproductive technologies. The results also showed that accounting for nonlinear associations between CpGs and gestational age improved gestational age prediction in preterm newborns. These findings contribute to an increased understanding of the relationship between DNA methylation, gestational age, fetal growth, and development in humans. The epigenetic gestational age clock is a valuable tool for further studies on epigenetic gestational age and developmental maturity.