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.
Highlights
IntroductionAs assessed through DNA methylation markers, is associated with several complex diseases
Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases
Seven DNA methylation age (DNAmAge) measures were evaluated. For four of these (Horvath, Hannum, PhenoAge, and GrimAge), DNAmAge estimates were higher than chronological age for both groups of women
Summary
As assessed through DNA methylation markers, is associated with several complex diseases. 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. 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. While there has been some success in the identification of maternal susceptibility genes for PE9–11 they do not explain all the heritability This indicates that other genomic factors, including epigenetic modifications, may be involved in predisposing some women to risk of developing PE. Eighteen of the original 353 CpGs were not included in our analyses as they are not available on the EPIC array
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