Epigenome-wide association data implicate fetal/maternal adaptations contributing to clinical outcomes in preeclampsia

Abstract

Aim: To investigate the changes of placental DNA methylome in preeclampsia (PE). Materials & methods: We performed an epigenome-wide association study in a Chinese cohort and six published datasets consisting of 335 samples in total. Results & conclusion: Numerous consistently hypomethylated probes were associated with early-onset PE in different populations, with 2125 reaching epigenome-wide significance. The validated probes were enriched for cytosine-phosphate-guanine dinucleotide (CpG) sites partially methylated and located in genes related to trophoblast fusion. The methylation levels of the validated probes were associated with clinical severity, while the intermediate samples showed antagonistic fetal/maternal outcomes. The DNA methylation patterns of PE and clinically relevant obstetrical syndromes suggested partially common pathophysiologies and complex maternal/fetal adaptive responses contributing to variable clinical outcomes.