DNA Methylation Trajectories During Pregnancy
There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P <.05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P <.05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.
Gruzieva, O., Merid, S., Chen, S., Mukherjee, N., Hedman, A., Almqvist, C., Andolf, E., Jiang, Y., Kere, J., Scheynius, A., Söderhäll, C., Ullemar, V., Karmaus, W., Melén, E., Arshad, S., & Pershagen, G. (2019). DNA Methylation Trajectories During Pregnancy. Epigenetics Insights, 12 https://doi.org/10.1177/2516865719867090