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Canouil, M.* ; Khamis, A.* ; Keikkala, E.* ; Hummel, S. ; Lobbens, S.* ; Bonnefond, A.* ; Delahaye, F.* ; Tzala, E.* ; Mustaniemi, S.* ; Vaarasmaki, M.* ; Jarvelin, M.R.* ; Sebert, S.* ; Kajantie, E.* ; Froguel, P.* ; Andrew, T.*

Epigenome-wide association study reveals methylation loci associated with offspring gestational diabetes mellitus exposure and maternal methylome.

Diabetes Care 44, 1992-1999 (2021)
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OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with an increased risk of obesity and insulin resistance in offspring later in life, which might be explained by epigenetic changes in response to maternal hyperglycemic exposure. RESEARCH DESIGN AND METHODS: We explored the association between GDM exposure and maternal blood and newborn cord blood methylation in 536 mother-offspring pairs from the prospective FinnGeDi cohort using Illumina MethylationEPIC 850K BeadChip arrays. We assessed two hypotheses. First, we tested for shared maternal and offspring epigenetic effects resulting from GDM exposure. Second, we tested whether GDM exposure and maternal methylation had an epigenetic effect on the offspring. RESULTS: We did not find any epigenetic marks (differentially methylated CpG probes) with shared and consistent effects between mothers and offspring. After including maternal methylation in the model, we identified a single significant (false discovery rate 1.38 × 10-2) CpG at the cg22790973 probe (TFCP2) associated with GDM. We identified seven additional FDR-significant interactions of maternal methylation and GDM status, with the strongest association at the same cg22790973 probe (TFCP2), as well as cg03456133, cg24440941 (H3C6), cg20002843 (LOC127841), cg19107264, and cg11493553 located within the UBE3C gene and cg17065901 in FAM13A, both susceptibility genes for type 2 diabetes and BMI, and cg23355087 within the DLGAP2 gene, known to be involved in insulin resistance during pregnancy. CONCLUSIONS: Our study reveals the potential complexity of the epigenetic transmission between mothers with GDM and their offspring, likely determined by not only GDM exposure but also other factors indicated by maternal epigenetic status, such as maternal metabolic history.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dna Methylation; Prevalence; Package; Women
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 44, Issue: 9, Pages: 1992-1999 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Reviewing status Peer reviewed
Grants Medical Research Council
Biotechnology and Biological Sciences Research Council