@article{c0d2230faefd4aeca32ab2d28cba9a38,
title = "Hypertensive disorders of pregnancy and DNA methylation in newborns: findings from the Pregnancy and Childhood Epigenetics Consortium",
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.",
keywords = "DNA methylation, cardiovascular diseases, gestational age, hypertension, preeclampsia, Genome-Wide Association Study, Epigenesis, Genetic, Humans, Hypertension, Pregnancy-Induced/diagnosis, DNA Methylation/genetics, Gestational Age, Pregnancy, DNA-Binding Proteins/genetics, Infant, Premature, Adult, Female, Fetal Blood, Infant, Newborn, Pregnancy Outcome, Cohort Studies",
author = "Nabila Kazmi and Sharp, {Gemma C.} and Reese, {Sarah E.} and Vehmeijer, {Florianne O.} and Jari Lahti and Page, {Christian M.} and Weiming Zhang and Rifas-shiman, {Sheryl L.} and Rezwan, {Faisal I} and Simpkin, {Andrew J.} and Kimberley Burrows and Richardson, {Tom G.} and Ferreira, {Diana L. Santos} and Abigail Fraser and Harmon, {Quaker E.} and Shanshan Zhao and Jaddoe, {Vincent W. V.} and Darina Czamara and Binder, {Elisabeth B.} and Magnus, {Maria C.} and H{\aa}berg, {Siri E.} and Wenche Nystad and Nohr, {Ellen A.} and Starling, {Anne P.} and Kechris, {Katerina J.} and Yang, {Ivana V.} and Demeo, {Dawn L.} and Litonjua, {Augusto A.} and Andrea Baccarelli and Emily Oken and Holloway, {John W.} and Wilfried Karmaus and Arshad, {Syed H.} and Dana Dabelea and S{\o}rensen, {Thorkild I.A.} and Hannele Laivuori and Katri Raikkonen and Felix, {Janine F.} and London, {Stephanie J.} and Marie-France Hivert and Gaunt, {Tom R.} and Lawlor, {Debbie A.} and Relton, {Caroline L.}",
note = "Funding Information: D.A. Lawlor has received support from Roche Diagnostics and Medtronic, as well as from government and charitable funding bodies to support research unrelated to that presented here. T.R. Gaunt receives funding from GlaxoSmithKline and Biogen for unrelated research projects. The other authors report no conflicts. Publisher Copyright: {\textcopyright} 2019 American Heart Association, Inc.",
year = "2019",
month = aug,
day = "1",
doi = "10.1161/HYPERTENSIONAHA.119.12634",
language = "English",
volume = "74",
pages = "375--383",
journal = "Hypertension",
issn = "1524-4563",
publisher = "American Heart Association",
number = "2",
}