Maternal gestational diabetes mellitus and newborn DNA Methylation: Findings from the pregnancy and childhood epigenetics consortium

Caitlin G. Howe, Bianca Cox, Ruby Fore, James Jungius, Tuomas Kvist, Samantha Lent, Harriet E. Miles, Lucas A. Salas, Sheryl Rifas-Shiman, Anne P. Starling, Paul Yousefi, Christine Ladd-Acosta, Andrea Baccarelli, Elisabeth B. Binder, Vaia Lida Chatzi, Darina Czamara, Dana Dabelea, Dawn L. DeMeo, Akram Ghantous, Zdenko HercegEero Kajantie, Jari M.T. Lahti, Debbie A. Lawlor, Augusto Litonjua, Tim S. Nawrot, Ellen A. Nohr, Emily Oken, Costanza Pizzi, Michelle Plusquin, Katri Räikkönen, Caroline L. Relton, Gemma C. Sharp, Thorkild I.A. Sørensen, Jordi Sunyer, Martine Vrijheid, Weiming Zhang, Marie France Hivert, Carrie V. Breton

Research output: Contribution to journalArticlepeer-review

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, usingDNAmethylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations betweenGDMandDNA 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 bodyof CYP2E1. IndividualCpGanalyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS MaternalGDMwas 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.

Original languageEnglish (US)
Pages (from-to)98-105
Number of pages8
JournalDiabetes care
Volume43
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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