TY - JOUR
T1 - Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns
T2 - Findings from the Pregnancy and Childhood Epigenetics Consortium
AU - Kazmi, Nabila
AU - Sharp, Gemma C.
AU - Reese, Sarah E.
AU - Vehmeijer, Florianne O.
AU - Lahti, Jari
AU - Page, Christian M.
AU - Zhang, Weiming
AU - Rifas-Shiman, Sheryl L.
AU - Rezwan, Faisal I.
AU - Simpkin, Andrew J.
AU - Burrows, Kimberley
AU - Richardson, Tom G.
AU - Santos Ferreira, Diana L.
AU - Fraser, Abigail
AU - Harmon, Quaker E.
AU - Zhao, Shanshan
AU - Jaddoe, Vincent W.V.
AU - Czamara, Darina
AU - Binder, Elisabeth B.
AU - Magnus, Maria C.
AU - Håberg, Siri E.
AU - Nystad, Wenche
AU - Nohr, Ellen A.
AU - Starling, Anne P.
AU - Kechris, Katerina J.
AU - Yang, Ivana V.
AU - Demeo, Dawn L.
AU - Litonjua, Augusto A.
AU - Baccarelli, Andrea
AU - Oken, Emily
AU - Holloway, John W.
AU - Karmaus, Wilfried
AU - Arshad, Syed H.
AU - Dabelea, Dana
AU - Sørensen, Thorkild I.A.
AU - Laivuori, Hannele
AU - Raikkonen, Katri
AU - Felix, Janine F.
AU - London, Stephanie J.
AU - Hivert, Marie France
AU - Gaunt, Tom R.
AU - Lawlor, Debbie A.
AU - Relton, Caroline L.
N1 - Publisher Copyright:
© 2019 American Heart Association, Inc.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - cardiovascular diseases
KW - gestational age
KW - hypertension
KW - preeclampsia
UR - https://www.scopus.com/pages/publications/85069621483
U2 - 10.1161/HYPERTENSIONAHA.119.12634
DO - 10.1161/HYPERTENSIONAHA.119.12634
M3 - Article
SN - 0194-911X
VL - 74
SP - 375
EP - 383
JO - Hypertension
JF - Hypertension
IS - 2
ER -
