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

Title: Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation : Findings From the Pregnancy and Childhood Epigenetics Consortium
Authors: Howe, Caitlin G.; Cox, Bianca; Fore, Ruby; Jungius, James; Kvist, Tuomas; Lent, Samantha; Miles, Harriet E.; Salas, Lucas A.; Rifas-Shiman, Sheryl; Starling, Anne P.; Yousefi, Paul; Ladd-Acosta, Christine; Baccarelli, Andrea; Binder, Elisabeth B.; Chatzi, Vaia Lida; Czamara, Darina; Dabelea, Dana; DeMeo, Dawn L.; Ghantous, Akram; Herceg, Zdenko; Kajantie, Eero; Lahti, Jari M. T.; Lawlor, Debbie A.; Litonjua, Augusto; Nawrot, Tim S.; Nohr, Ellen A.; Oken, Emily; Pizzi, Costanza; Plusquin, Michelle; Räikkönen, Katri; Relton, Caroline L.; Sharp, Gemma C.; Sorensen, Thorkild I. A.; Sunyer, Jordi; Vrijheid, Martine; Zhang, Weiming; Hivert, Marie-France; Breton, Carrie V.
Contributors: Department of Psychology and Logopedics; Developmental Psychology Research Group; University of Helsinki; HUS Children and Adolescents; Clinicum; Lastentautien yksikkö; Children's Hospital
Publisher Information: American Diabetes Association Inc.
Publication Year: 2021
Collection: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
Subject Terms: CORD BLOOD; ASSOCIATION; GENES; CLASSIFICATION; HYPERGLYCEMIA; DIAGNOSIS; CRITERIA; Biomedicine; General medicine; internal medicine and other clinical medicine
Description: 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. ; Peer reviewed
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://hdl.handle.net/10138/327661; 000508573600025
Availability: https://hdl.handle.net/10138/327661
Rights: unspecified ; info:eu-repo/semantics/openAccess ; openAccess
Accession Number: edsbas.2EBB5F78
Database: BASE