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

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Howe , C G , Cox , B , Fore , R , Jungius , J , Kvist , T , Lent , S , Miles , H E , Salas , L A , Rifas-Shiman , S , Starling , A P , Yousefi , P , Ladd-Acosta , C , Baccarelli , A , Binder , E B , Chatzi , V L , Czamara , D , Dabelea , D , DeMeo , D L , Ghantous , A , Herceg , Z , Kajantie , E , Lahti , J M T , Lawlor , D A , Litonjua , A , Nawrot , T S , Nohr , E A , Oken , E , Pizzi , C , Plusquin , M , Räikkönen , K , Relton , C L , Sharp , G C , Sorensen , T I A , Sunyer , J , Vrijheid , M , Zhang , W , Hivert , M-F & Breton , C V 2020 , ' Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation : Findings From the Pregnancy and Childhood Epigenetics Consortium ' , Diabetes Care , vol. 43 , no. 1 , pp. 98-105 . https://doi.org/10.2337/dc19-0524

Title: Maternal Gestational Diabetes Mellitus and Newborn DNA Methylation : Findings From the Pregnancy and Childhood Epigenetics Consortium
Author: 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.
Contributor: University of Helsinki, Department of Psychology and Logopedics
University of Helsinki, HUS Children and Adolescents
University of Helsinki, University of Bristol
University of Helsinki, University of Bristol
Date: 2020-01
Language: eng
Number of pages: 8
Belongs to series: Diabetes Care
ISSN: 0149-5992
URI: http://hdl.handle.net/10138/327661
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.
Subject: CORD BLOOD
ASSOCIATION
GENES
CLASSIFICATION
HYPERGLYCEMIA
DIAGNOSIS
CRITERIA
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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