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. Magnus; Siri 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

doi:10.1161/HYPERTENSIONAHA.119.12634

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. Magnus

Siri 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

University of Bristol
Bristol Medical School
National Institute of Environmental Health Sciences (NIEHS)
Erasmus MC
University of Helsinki
University of Helsinki
Norwegian Institute of Public Health
Oslo University Hospital
University of Colorado Anschutz Medical Campus
Harvard Medical School
University of Southampton, Faculty of Medicine
Max Planck Institute of Psychiatry
Emory University School of Medicine
University of Southern Denmark
University of Colorado School of Medicine
National Jewish Health
University of Rochester Medical Center
Mailman School of Public Health
University of Memphis
University of Colorado Department of Pediatrics
Novo Nordisk Foundation Center for Basic Metabolic Research
University of Copenhagen
University of Tampere
Tampere University Hospital
Massachusetts General Hospital
Bristol NIHR Biomedical Research Centre

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

93 Citations (Scopus)

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 language	English
Pages (from-to)	375-383
Number of pages	9
Journal	Hypertension
Volume	74
Issue number	2
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.119.12634
Publication status	Published - 1 Aug 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

DNA methylation
cardiovascular diseases
gestational age
hypertension
preeclampsia

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10.1161/HYPERTENSIONAHA.119.12634

Cite this

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

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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",

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 \{Santos Ferreira\}, \{Diana L.\} 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 Hivert, \{Marie France\} and Gaunt, \{Tom R.\} and Lawlor, \{Debbie A.\} and Relton, \{Caroline L.\}",

note = "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 = "0194-911X",

publisher = "Lippincott Williams and Wilkins",

number = "2",

}

Kazmi, N, Sharp, GC, Reese, SE, Vehmeijer, FO, Lahti, J, Page, CM, Zhang, W, Rifas-Shiman, SL, Rezwan, FI, Simpkin, AJ, Burrows, K, Richardson, TG, Santos Ferreira, DL, Fraser, A, Harmon, QE, Zhao, S, Jaddoe, VWV, Czamara, D, Binder, EB, Magnus, MC, Håberg, SE, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, Demeo, DL, Litonjua, AA, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, SH, Dabelea, D, Sørensen, TIA, Laivuori, H, Raikkonen, K, Felix, JF, London, SJ, Hivert, MF, Gaunt, TR, Lawlor, DA & Relton, CL 2019, 'Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns: Findings from the Pregnancy and Childhood Epigenetics Consortium', Hypertension, vol. 74, no. 2, pp. 375-383. https://doi.org/10.1161/HYPERTENSIONAHA.119.12634

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.

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 -

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

Abstract

UN SDGs

Keywords

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