Evaluation of epigenetic age calculators between preeclampsia and normotensive pregnancies in an Australian cohort

Paulina Pruszkowska-Przybylska; Shaun Brennecke; Eric K Moses; Phillip E Melton

doi:10.1038/s41598-022-05744-4

Evaluation of epigenetic age calculators between preeclampsia and normotensive pregnancies in an Australian cohort

Sci Rep. 2022 Jan 31;12(1):1664. doi: 10.1038/s41598-022-05744-4.

Authors

Paulina Pruszkowska-Przybylska¹, Shaun Brennecke^{2

3}, Eric K Moses^{4

5}, Phillip E Melton^{4

6}

Affiliations

¹ Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, 90-237, Łódź, Poland. paulina.pruszkowska@biol.uni.lodz.pl.
² Pregnancy Research Centre, Department of Maternal-Fetal Medicine, Royal Women's Hospital, Melbourne, VIC, Australia.
³ Department of Obstetrics and Gynaecology, The Royal Women's Hospital, The University of Melbourne, Melbourne, VIC, Australia.
⁴ Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
⁵ School of Global Population Health, University of Western Australia, Perth, Australia.
⁶ School of Biomedical Science, University of Western Australia, Perth, Australia.

Abstract

Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases. The associations between maternal DNA methylation age and preeclampsia (PE) have not been fully assessed. The aim of this study was to examine if increased maternal DNA methylation age (DNAmAge) was shown to be accelerated in women with PE when compared to women who had normotensive pregnancies. The case/control cohort available for study consisted of 166 women (89 with normotensive pregnancy, 77 with PE) recruited previously at the Royal Women's Hospital in Melbourne, Australia. DNA methylation profiles were obtained using the Illumina EPIC Infinium array for analysis of genomic DNA isolated from whole blood. These profiles were used to calculate seven estimates of DNAmAge and included (1) Horvath, (2) Hannum, (3) Horvath Skin and Blood, (4) Wu, (5) PhenoAge, (6) telomere length and (7) GrimAge and its surrogate measures. Three measures of DNA methylation age acceleration were calculated for all seven measures using linear regression. Pearson's correlation was performed to investigate associations between chronological age and DNAmAge. Differences between chronological age and DNAmAge and epigenetic age acceleration were investigated using t-tests. No significant difference was observed for chronological age between women with PE (age = 30.53 ± 5.68) and women who had normotensive pregnancies (age = 31.76 ± 4.76). All seven DNAmAge measures were significantly correlated (p < 0.001) with chronological age. After accounting for multiple testing and investigating differences in DNAmAge between normotensive women and women with PE, only Wu DNAmAge was significant (p = 0.001). When examining differences for epigenetic age acceleration between PE and normotensive women Hannum, Wu, and PhenoAge DNAmAge estimates (p < 0.001) were significant for both epigenetic age acceleration and intrinsic acceleration models. We found that accelerated maternal DNAmAge is increased in women with PE in some models of epigenetic aging. This research underlines the importance for further investigation into the potential changes of differential DNA methylation in PE.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Blood Pressure / genetics*
Cellular Senescence / genetics*
DNA Methylation*
Epigenesis, Genetic*
Female
Genotype
Humans
Maternal Age
Phenotype
Pre-Eclampsia / diagnosis
Pre-Eclampsia / genetics*
Pre-Eclampsia / physiopathology
Pregnancy
Retrospective Studies
Risk Assessment
Risk Factors
Telomere Shortening / genetics
Victoria