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Hypertensive disorders of pregnancy and DNA methylation in newborns: findings from the Pregnancy and Childhood Epigenetics Consortium

Hypertensive disorders of pregnancy and DNA methylation in newborns: findings from the Pregnancy and Childhood Epigenetics Consortium
Hypertensive disorders of pregnancy and DNA methylation in newborns: findings from the Pregnancy and Childhood Epigenetics Consortium
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.
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Kazmi, Nabila, Sharp, Gemma C., Reese, Sarah E., Vehmeijer, Florianne O., Lahti, Jari, Page, Christian M., Zhang, Weiming, Rifas-shiman, Sheryl L., Rezwan, Faisal I., Simpkin, Andrew J., Burrows, Kimberley, Richardson, Tom G., Santos Ferreira, Diana L., Fraser, Abigail, Harmon, Quaker E., Zhao, Shanshan, Jaddoe, Vincent W.V., Czamara, Darina, Binder, Elisabeth B., Magnus, Maria C., Håberg, Siri E., Nystad, Wenche, Nohr, Ellen A., Starling, Anne P., Kechris, Katerina J., Yang, Ivana V., Demeo, Dawn L., Litonjua, Augusto A., Baccarelli, Andrea, Oken, Emily, Holloway, John W., Karmaus, Wilfried, Arshad, Syed H., Dabelea, Dana, Sørensen, Thorkild I.A., Laivuori, Hannele, Raikkonen, Katri, Felix, Janine F., London, Stephanie J., Hivert, Marie-France, Gaunt, Tom R., Lawlor, Debbie A. and Relton, Caroline L. (2019) Hypertensive disorders of pregnancy and DNA methylation in newborns: findings from the Pregnancy and Childhood Epigenetics Consortium. Hypertension, 74 (2), 375-383. (doi:10.1161/HYPERTENSIONAHA.119.12634).

Record type: Article

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.

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HYPERTENSIONAHA.119.12634 - Version of Record
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Accepted/In Press date: 13 May 2019
e-pub ahead of print date: 24 June 2019
Published date: 1 August 2019

Identifiers

Local EPrints ID: 432253
URI: http://eprints.soton.ac.uk/id/eprint/432253
ISSN: 0194-911X
PURE UUID: 1818726c-f552-484a-b0e5-894650314398
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 05 Jul 2019 16:30
Last modified: 26 Nov 2021 03:00

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Contributors

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

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