Epigenomic Markers for Heritable Risk of Preeclampsia

Preeclampsia (PE) affects 8–10% of women in the US. Long-term consequences include development of maternal hypertension and hypertension in offspring. The familial risk of PE is well established, though underlying mechanisms are unknown. In this study, our goal was to identify differentially methylated genes common to both maternal peripheral blood cells (MPBCs) and placental tissue of fetal origin in order to determine potential epigenomic markers of heritable PE risk. Methylation quantification of individual CpG dinucleotides in MPBCs and placental tissue from women with and without PE was determined using the Illumina Infinium methylation array (n=6/group). Gain of methylation was seen in 218 CpG dinucleotides from MPBCs, and ~34% of these changes were also present in placenta. Significant methylation loss was observed in 123 CpG dinucleotides, and ~28% of changes were also present in placenta. Validation of methylation was determined by bisulfite sequencing. Differentially methylated loci were primarily located in non-CpG island regions of genes with known roles in angiogenesis, inflammation and metabolic regulation. This study provides novel evidence for the mechanisms underlying heritable risk for PE, implicating differential transgenerational DNA methylation in key genes associated with the etiology and consequences of PE and suggest that these may serve as novel biomarkers for PE screening.