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


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.

SUBMITTER: Howe CG 

PROVIDER: S-EPMC6925578 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Howe Caitlin G CG   Cox Bianca B   Fore Ruby R   Jungius James J   Kvist Tuomas T   Lent Samantha S   Miles Harriet E HE   Salas Lucas A LA   Rifas-Shiman Sheryl S   Starling Anne P AP   Yousefi Paul P   Ladd-Acosta Christine C   Baccarelli Andrea A   Binder Elisabeth B EB   Chatzi Vaia Lida VL   Czamara Darina D   Dabelea Dana D   DeMeo Dawn L DL   Ghantous Akram A   Herceg Zdenko Z   Kajantie Eero E   Lahti Jari M T JMT   Lawlor Debbie A DA   Litonjua Augusto A   Nawrot Tim S TS   Nohr Ellen A EA   Oken Emily E   Pizzi Costanza C   Plusquin Michelle M   Räikkönen Katri K   Relton Caroline L CL   Sharp Gemma C GC   Sørensen Thorkild I A TIA   Sunyer Jordi J   Vrijheid Martine M   Zhang Weiming W   Hivert Marie-France MF   Breton Carrie V CV  

Diabetes care 20191010 1


<h4>Objective</h4>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.<h4>Research design and methods</h4>Seven pregnancy cohorts (3,677 mother-newbo  ...[more]

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