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An Exploratory Study of Epigenetic Age in Preeclamptic and Normotensive Pregnancy Reveals Differences by Self-Reported Race but Not Pregnancy Outcome

  • Genetics: Original Article
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Abstract

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with preeclampsia, but the role of these factors is not entirely understood. We hypothesized that DNA methylation age, a measure of biological age, would be higher in individuals with preeclampsia than in individuals with normotensive pregnancy and that DNA methylation age would differ by race across pregnancy. This was a longitudinal, exploratory study of 56 pregnant individuals (n = 28 preeclampsia cases and n = 28 normotensive controls). Genome-wide DNA methylation data were generated from trimester-specific peripheral blood samples. DNA methylation age was estimated using the “Improved Precision” clock, and ∆age, the difference between DNA methylation age and chronological age, was computed. DNA methylation age was compared with chronological age using Pearson correlations. The relationships between ∆age and preeclampsia status, self-reported race, and covariates were tested using multiple linear regression and performed both with and without consideration of cell-type heterogeneity. We observed strong correlation between chronological age and DNA methylation age across pregnancy, with significantly stronger correlation observed in White participants than in Black participants. We observed no association between ∆age and preeclampsia status. However, ∆age was higher in participants with higher pre-pregnancy body mass index in trimester 1 and lower in Black participants than in White participants in trimesters 2 and 3. Observations were largely consistent when controlling for cell-type heterogeneity. Our findings in a small sample support the need for additional studies to investigate the relationship between race and biological age, which could provide further insight into racial disparities across pregnancy. However, this study does not support an association between ∆age and preeclampsia status.

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Data Availability

dbGAP, accession number: phs001937.v1.p1

Code Availability

The “Improved Precision” epigenetic clock is available through publicly available source code as cited in the paper and located in GitHub at https://github.com/qzhang314/DNAm-based-age-predictor.

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Acknowledgements

We would like to thank the participants for their involvement in this research and Sandra Deslouches, laboratory manager at the University of Pittsburgh School of Nursing, for her expertise and assistance in sample preparation. We would also like to thank the anonymous reviewers who took the time to critically evaluate this paper as their feedback improved the clarity of this work.

Funding

Research reported in this publication was supported by the National Institute of Child Health and Human Development (R21HD092770 and P01HD303067), the National Center for Advancing Translational Sciences (TL1TR001858), and the National Institute of Nursing Research (T32NR009759) of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA, 15261, USA

    Lacey W. Heinsberg, Yvette P. Conley & Daniel E. Weeks

  2. Division of Internal Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Lacey W. Heinsberg

  3. Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Lacey W. Heinsberg, James M. Roberts & Arun Jeyabalan

  4. Department of Health Promotion and Development, School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA

    Mitali Ray, Yvette P. Conley & Mandy J. Schmella

  5. Department of Obstetrics, Gynecology, & Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    James M. Roberts, Arun Jeyabalan & Carl A. Hubel

  6. Magee-Womens Research Institute, Pittsburgh, PA, USA

    James M. Roberts, Arun Jeyabalan & Carl A. Hubel

  7. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    James M. Roberts

  8. Global Pregnancy Collaboration, Pittsburgh, PA, USA

    James M. Roberts & Arun Jeyabalan

  9. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Daniel E. Weeks

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  1. Lacey W. Heinsberg
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Contributions

Lacey W. Heinsberg contributed to the study conception and design and analysis and interpretation of the data and drafted, critically revised, and gave final approval for the manuscript. Mitali Ray contributed to the study conception and design and interpretation of the data and critically revised and gave final approval for the manuscript. Yvette P. Conley contributed to the interpretation of the data and critically revised and gave final approval for the manuscript. James M. Roberts contributed to the acquisition and interpretation of the data and critically revised and gave final approval for the manuscript. Arun Jeyabalan contributed to the acquisition and interpretation of the data and critically revised and gave final approval for the manuscript. Carl A. Hubel contributed to the acquisition and interpretation of the data and critically revised and gave final approval for the manuscript. Daniel E. Weeks contributed to the study conception and design and analysis and interpretation of the data and critically revised and gave final approval for the manuscript. Mandy J. Schmella contributed to the study conception and design and acquisition and interpretation of the data and critically revised and gave final approval for the manuscript.

Corresponding author

Correspondence to Lacey W. Heinsberg.

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Ethical Approval

This study has Institutional Review Board Approval from the University of Pittsburgh (Study number 19110285, most recent renewal approved 11-25-2020).

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Written informed consent was obtained from all participants at enrollment.

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Heinsberg, L.W., Ray, M., Conley, Y.P. et al. An Exploratory Study of Epigenetic Age in Preeclamptic and Normotensive Pregnancy Reveals Differences by Self-Reported Race but Not Pregnancy Outcome. Reprod. Sci. 28, 3519–3528 (2021). https://doi.org/10.1007/s43032-021-00575-6

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  • DOI: https://doi.org/10.1007/s43032-021-00575-6

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