Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns: Findings From the Pregnancy and Childhood Epigenetics Consortium

Nabila Kazmi, Gemma C. Sharp, Sarah E. Reese, Florianne O. Vehmeijer, Jari Lahti, Christian M. Page, Weiming Zhang, Sheryl L. Rifas-Shiman, Faisal I. Rezwan, Andrew J. Simpkin, Kimberley Burrows, Tom G. Richardson, Diana L. Santos Ferreira, Abigail Fraser, Quaker E. Harmon, Shanshan Zhao, Vincent W.V. Jaddoe, Darina Czamara, Elisabeth B. Binder, Maria C. MagnusSiri E. Håberg, Wenche Nystad, Ellen A. Nohr, Anne P. Starling, Katerina J. Kechris, Ivana V. Yang, Dawn L. DeMeo, Augusto A. Litonjua, Andrea Baccarelli, Emily Oken, John W. Holloway, Wilfried Karmaus, Syed H. Arshad, Dana Dabelea, Thorkild I.A. Sørensen, Hannele Laivuori, Katri Raikkonen, Janine F. Felix, Stephanie J. London, Marie France Hivert, Tom R. Gaunt, Debbie A. Lawlor, Caroline L. Relton

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Abstract

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

Original languageEnglish
Pages (from-to)375-383
Number of pages9
JournalHypertension
Volume74
Issue number2
Early online date24 Jun 2019
DOIs
Publication statusPublished - 1 Aug 2019

Structured keywords

  • ALSPAC

Keywords

  • ALSPAC
  • gestational hypertension
  • pre-eclampsia
  • hypertension
  • DNA
  • methylation
  • epigenetics

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    Kazmi, N., Sharp, G. C., Reese, S. E., Vehmeijer, F. O., Lahti, J., Page, C. M., Zhang, W., Rifas-Shiman, S. L., Rezwan, F. I., Simpkin, A. J., Burrows, K., Richardson, T. G., Santos Ferreira, D. L., Fraser, A., Harmon, Q. E., Zhao, S., Jaddoe, V. W. V., Czamara, D., Binder, E. B., ... Relton, C. L. (2019). Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns: Findings From the Pregnancy and Childhood Epigenetics Consortium. Hypertension, 74(2), 375-383. https://doi.org/10.1161/HYPERTENSIONAHA.119.12634