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Hypertension. 2019 Aug;74(2):375-383. doi: 10.1161/HYPERTENSIONAHA.119.12634. Epub 2019 Jun 24.

Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns.

Author information

1
From the MRC Integrative Epidemiology Unit (N.K., G.C.S., A.J.S., K.B., T.G.R., D.L.S.F., A.F., M.C.M., T.I.A.S., T.R.G., D.A.L., C.L.R.), University of Bristol, United Kingdom.
2
Population Health Sciences, Bristol Medical School (N.K., G.C.S., K.B., T.G.R., D.L.S.F., A.F., M.C.M., T.R.G., D.A.L., C.L.R.), University of Bristol, United Kingdom.
3
School of Oral and Dental Sciences (G.C.S.), University of Bristol, United Kingdom.
4
Division of Intramural Research, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC (S.E.R., Q.E.H., S.Z., S.J.L.).
5
The Generation R Study Group (F.O.V., V.W.V.J., J.F.F.), Erasmus MC, University Medical Center Rotterdam, the Netherlands.
6
Department of Epidemiology (F.O.V., V.W.V.J., J.F.F.), Erasmus MC, University Medical Center Rotterdam, the Netherlands.
7
Department of Pediatrics (F.O.V., V.W.V.J., J.F.F.), Erasmus MC, University Medical Center Rotterdam, the Netherlands.
8
Department of Psychology and Logopedics, Faculty of Medicine (J.L., K.R.), University of Helsinki, Finland.
9
Helsinki Collegium of Advanced Studies (J.L.), University of Helsinki, Finland.
10
Division of Mental and Physical Health (C.M.P., W.N.), Norwegian Institute of Public Health, Oslo.
11
Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Norway (C.M.P.).
12
Department of Biostatistics and Informatics (W.Z., K.J.K.), University of Colorado Anschutz Medical Campus, Aurora.
13
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA (S.L.R.-S., E.O., M.-F.H.).
14
Human Development and Health (F.I.R., J.W.H.), Faculty of Medicine University of Southampton, United Kingdom.
15
Insight Centre for Data Analytics, National University of Ireland, Galway (A.J.S.).
16
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany (D.C., E.B.B.).
17
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (E.B.B.).
18
Centre for Fertility and Health (M.C.M., S.E.H.), Norwegian Institute of Public Health, Oslo.
19
Research Unit of Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense (E.A.N.).
20
Department of Epidemiology (A.P.S., I.V.Y., D.D.), University of Colorado Anschutz Medical Campus, Aurora.
21
Department of Medicine (I.V.Y.), University of Colorado Anschutz Medical Campus, Aurora.
22
Center for Genes, Environment and Health, National Jewish Health, Denver, CO (I.V.Y.).
23
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.L.D.).
24
Division of Pediatric Pulmonary Medicine, University of Rochester Medical Center, NY (A.A.L.).
25
Laboratory of Precision Environmental Biosciences, Columbia University Mailman School of Public Health, New York, NY (A.B.).
26
Clinical and Experimental Sciences (J.W.H., S.H.A.), Faculty of Medicine University of Southampton, United Kingdom.
27
Division of Epidemiology, Biostatistics, and Environmental Health, School of Public Health, University of Memphis, TN (W.K.).
28
Department of Pediatrics (D.D.), University of Colorado Anschutz Medical Campus, Aurora.
29
Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics (T.I.A.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
30
Department of Public Health, Section on Epidemiology (T.I.A.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
31
Institute for Molecular Medicine Finland, Helsinki Institute of Life Science (H.L.), University of Helsinki, Finland.
32
Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Finland (H.L.).
33
Faculty of Medicine and Life Sciences, University of Tampere, Finland (H.L.).
34
Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland (H.L.).
35
Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki. Finland (H.L.).
36
Diabetes Unit, Massachusetts General Hospital, Boston, MA (M.-F.H.).
37
NIHR Bristol Biomedical Research Centre, Bristol, United Kingdom (T.R.G., D.A.L., C.L.R.).

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

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