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DNA methylation signatures link prenatal famine exposure to growth and metabolism

Author

Listed:
  • Elmar W. Tobi

    (Molecular Epidemiology, Leiden University Medical Center)

  • Jelle J. Goeman

    (Medical Statistics and Bioinformatics, Leiden University Medical Center
    Present address: Biostatistics, Department for Health Evidence, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands)

  • Ramin Monajemi

    (Medical Statistics and Bioinformatics, Leiden University Medical Center)

  • Hongcang Gu

    (The Broad Institute of MIT and Harvard)

  • Hein Putter

    (Medical Statistics and Bioinformatics, Leiden University Medical Center)

  • Yanju Zhang

    (Molecular Epidemiology, Leiden University Medical Center)

  • Roderick C. Slieker

    (Molecular Epidemiology, Leiden University Medical Center)

  • Arthur P. Stok

    (Molecular Epidemiology, Leiden University Medical Center)

  • Peter E. Thijssen

    (Molecular Epidemiology, Leiden University Medical Center
    Human Genetics, Leiden University Medical Center)

  • Fabian Müller

    (Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics)

  • Erik W. van Zwet

    (Medical Statistics and Bioinformatics, Leiden University Medical Center)

  • Christoph Bock

    (Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics
    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences
    Medical University of Vienna)

  • Alexander Meissner

    (The Broad Institute of MIT and Harvard
    Harvard University)

  • L. H. Lumey

    (Molecular Epidemiology, Leiden University Medical Center
    Mailman School of Public Health, Columbia University)

  • P. Eline Slagboom

    (Molecular Epidemiology, Leiden University Medical Center)

  • Bastiaan T. Heijmans

    (Molecular Epidemiology, Leiden University Medical Center)

Abstract

Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.

Suggested Citation

  • Elmar W. Tobi & Jelle J. Goeman & Ramin Monajemi & Hongcang Gu & Hein Putter & Yanju Zhang & Roderick C. Slieker & Arthur P. Stok & Peter E. Thijssen & Fabian Müller & Erik W. van Zwet & Christoph Boc, 2014. "DNA methylation signatures link prenatal famine exposure to growth and metabolism," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6592
    DOI: 10.1038/ncomms6592
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    Cited by:

    1. Daniel E. Vosberg & Igor Jurisica & Zdenka Pausova & Tomáš Paus, 2024. "Intrauterine growth and the tangential expansion of the human cerebral cortex in times of food scarcity and abundance," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    2. Denny Vågerö & Agneta Cederström & Gerard J. Berg, 2022. "Food abundance in men before puberty predicts a range of cancers in grandsons," Nature Communications, Nature, vol. 13(1), pages 1-9, December.

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