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Maternal Gestational Diabetes and Newborn DNA Methylation: Findings from the Pregnancy and Childhood Epigenetics Consortium

Research output: Contribution to journalArticle

Original languageEnglish
Article numberdc190524
Number of pages8
JournalDiabetes Care
Early online date10 Oct 2019
DOIs
DateAccepted/In press - 17 Sep 2019
DateE-pub ahead of print (current) - 10 Oct 2019

Abstract

Background
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 Consortium.

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 array. Associations between GDM and DNA methylation were examined using robust linear regression, adjusting 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 controls. One DMR (chr1:248100345-248100614) was located in the OR2L13 promoter and the other (chr10:135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a PFDR 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.

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Diabetes Association at https://care.diabetesjournals.org/content/early/2019/10/09/dc19-0524. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 246 KB, PDF document

  • Supplementary information PDF

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Diabetes Association at https://care.diabetesjournals.org/content/early/2019/10/09/dc19-0524. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 2 MB, multipart/x-zip

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