title: Maternal gestational diabetes is associated with genome-wide DNA methylation variation in placenta and cord blood of exposed offspring.
abstract: Exposure of a developing foetus to maternal gestational diabetes (GDM) has been shown to programme future risk of diabetes and obesity. Epigenetic variation in foetal tissue may have a mechanistic role in metabolic disease programming through interaction of the pregnancy environment with gene function. We aimed to identify genome-wide DNA methylation variation in cord blood and placenta from offspring born to mothers with and without GDM. Pregnant women of South Asian origin were studied and foetal tissues sampled at term delivery. The Illumina HumanMethylation450 BeadChip was used to assay genome-wide DNA methylation in placenta and cord blood from 27 GDM exposed and 21 unexposed offspring. We identified 1485 cord blood and 1708 placenta methylation variable positions (MVPs) achieving genome-wide significance (adjusted P-value <0.05) with methylation differences of >5%. MVPs were disproportionately located within first exons. A bioinformatic co-methylation algorithm was used to detect consistent directionality of methylation in 1000 bp window around each MVP was observed at 74% of placenta and 59% of cord blood MVPs. KEGG pathway analysis showed enrichment of pathways involved in endocytosis, MAPK signalling and extracellular triggers to intracellular metabolic processes. Replication studies should integrate genomics and transcriptomics with longitudinal sampling to elucidate stability, determine causality for translation into biomarker and prevention studies.
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK Wellcome Trust-MRC Institute of Metabolic Sciences, University of Cambridge, Cambridge CB2 0QQ, UK and sf494@medschl.cam.ac.uk.
authors: Sarah
authors: S
authors: Finer
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Chris
authors: C
authors: Mathews
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Rob
authors: R
authors: Lowe
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Melissa
authors: M
authors: Smart
authors: Institute for Women's Health, University College London, London WC1E 6AU, UK.
authors: Sara
authors: S
authors: Hillman
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Lin
authors: L
authors: Foo
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Ajay
authors: A
authors: Sinha
authors: Institute for Women's Health, University College London, London WC1E 6AU, UK.
authors: David
authors: D
authors: Williams
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Vardhman K
authors: VK
authors: Rakyan
authors: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
authors: Graham A
authors: GA
authors: Hitman
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D016640:Diabetes, Gestational / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011256:Pregnancy Outcome; D017422:Sequence Analysis, DNA; D055815:Young Adult