Association of placental weight and placental-fetal weight ratio with DNA methylation in placenta.

To investigate the association between placental methylation and placenta weight (PW) and placental-fetal weight ratio (PFR), which are markers of placental function linked to adverse pregnancy outcomes and risk for diseases in later life. We examined the association between placental epigenome-wide methylation and PW and PFR at birth (n = 301). Further tests assessed whether methylation levels of the cytosine-guanine sites (CpGs) linked to PW and PFR are associated with placental expression of nearby genes. At a 5% false discovery rate (FDR), methylation at 27 CpGs was associated with PW, of which two CpGs were also associated with PFR. Methylation at four of the 27 CpGs was associated with placental expression of nearby genes including LEPR, RPS6KA1, and COX5A which have known roles in early development, cellular growth, and oxidative stress. The identified CpGs overlap with previously reported methylation sites associated with perinatal and adult health outcomes such as preeclampsia, preterm delivery, obesity, and type 2 diabetes. The findings reveal epigenetic underpinnings of placental development and functional efficiency, and suggest their potential roles in mediating fetal development and late-onset diseases.