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Diabetes Care. 2019 Oct 10. pii: dc190524. doi: 10.2337/dc19-0524. [Epub ahead of print]

Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation: Findings From the Pregnancy and Childhood Epigenetics Consortium.

Author information

1
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA caitlin.howe@usc.edu.
2
Center for Environmental Sciences, Hasselt University, Hasselt, Belgium.
3
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA.
4
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, U.K.
5
Population Health Science, Bristol Medical School, University of Bristol, Bristol, U.K.
6
Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
7
Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, NH.
8
ISGlobal, Barcelona, Spain.
9
Universitat Pompeu Fabra, Barcelona, Spain.
10
Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.
11
Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus, Aurora, CO.
12
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
13
Laboratory of Precision Environmental Biosciences, Columbia University Mailman School of Public Health, New York, NY.
14
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, Munich, Germany.
15
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA.
16
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
17
Department of Social Medicine, University of Crete, Heraklion, Crete, Greece.
18
Department of Genetics and Cell Biology, Maastricht University, Maastricht, the Netherlands.
19
Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO.
20
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
21
Epigenetics Group, International Agency for Research on Cancer, Lyon, France.
22
National Institute for Health and Welfare, Helsinki, Finland.
23
Research Unit for Pediatrics, Dermatology, Clinical Genetics, Obstetrics and Gynecology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
24
Department of Clinical and Molecular Medicine, Norwegian University for Science and Technology, Trondheim, Norway.
25
Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
26
Bristol National Institute of Health Research Biomedical Research Centre, Bristol, U.K.
27
Department of Public Health and Primary Care, Leuven University, Leuven, Belgium.
28
Research Unit for Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
29
Department of Medical Sciences, University of Turin, Turin, Italy.
30
Section on Metabolic Genetics, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
31
Section of Epidemiology, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
32
CIBER Epidemiología y Salud Pública, Madrid, Spain.
33
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.
34
Diabetes Unit, Massachusetts General Hospital, Boston, MA.

Abstract

OBJECTIVE:

Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium.

RESEARCH DESIGN AND METHODS:

Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate.

RESULTS:

Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05.

CONCLUSIONS:

Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.

PMID:
31601636
DOI:
10.2337/dc19-0524

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