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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)375-383
Number of pages9
JournalHypertension
Volume74
Issue number2
Early online date24 Jun 2019
DOIs
DateAccepted/In press - 13 May 2019
DateE-pub ahead of print - 24 Jun 2019
DatePublished (current) - 1 Aug 2019

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.

    Research areas

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

    Structured keywords

  • ALSPAC

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via AHA at https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.119.12634 . Please refer to any applicable terms of use of the publisher.

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