Placenta DNA methylation at ZNF300 is associated with fetal sex and placental morphology

Christine Ladd‐Acosta; Shan V. Andrews; Kelly M. Bakulski; Jason I. Feinberg; Rakel Tryggvadóttir; Ruofan Yao; Lisa Croen; Irva Hertz‐Picciotto; Craig J. Newschaffer; Carolyn M. Salafia; Andrew P. Feinberg; Kasper D. Hansen; M. Daniele Fallin

doi:10.1101/2021.03.05.433992

GenomicsbioRxivMar 5, 2021

Preprint

Placenta DNA methylation at ZNF300 is associated with fetal sex and placental morphology

Christine Ladd‐Acosta iD, Shan V. Andrews iD, Kelly M. Bakulski iD, Jason I. Feinberg iD, Rakel Tryggvadóttir iD, Ruofan Yao iD, Lisa Croen iD, Irva Hertz‐Picciotto iD, Craig J. Newschaffer iD, Carolyn M. Salafia iD, Andrew P. Feinberg iD, Kasper D. Hansen iD, M. Daniele Fallin iD

Abstract

Fetal sex-specific differences in placental morphology and physiology have been associated with sexually dimorphic health outcomes. However, the molecular mechanisms underlying these sex differences are not well understood. We performed whole genome bisulfite sequencing in 133 placenta samples and discovered a significant difference in DNA methylation (DNAm) at the ZNF300 gene locus between male and female offspring and replicated this result in 6 independent datasets. Additionally, the sex-specific pattern appears to be placenta-specific, is robust to a wide range of gestational ages and adverse health outcomes and is present in sorted placenta villous cytotrophoblast cells. Integration of DNAm, genetic, and placental morphology data from the same individuals revealed ZNF300 methylation is also associated with placenta area, perimeter, and max diameter, genetic variants on chromosomes 5 and X, and may mediate the effects of genetic variation on placental area.

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