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Genetic and environmental influences interact with age and sex in shaping the human methylome

Author

Listed:
  • Jenny van Dongen

    (VU Amsterdam)

  • Michel G. Nivard

    (VU Amsterdam)

  • Gonneke Willemsen

    (VU Amsterdam)

  • Jouke-Jan Hottenga

    (VU Amsterdam)

  • Quinta Helmer

    (VU Amsterdam)

  • Conor V. Dolan

    (VU Amsterdam)

  • Erik A. Ehli

    (Avera Institute for Human Genetics)

  • Gareth E. Davies

    (Avera Institute for Human Genetics)

  • Maarten van Iterson

    (Leiden University Medical Center)

  • Charles E. Breeze

    (UCL Cancer Institute, University College London)

  • Stephan Beck

    (UCL Cancer Institute, University College London)

  • H. Eka Suchiman

    (Leiden University Medical Center)

  • Rick Jansen

    (VU University Medical Center)

  • Joyce B. van Meurs

    (Erasmus Medical Center)

  • Bastiaan T. Heijmans

    (Leiden University Medical Center)

  • P. Eline Slagboom

    (Leiden University Medical Center)

  • Dorret I. Boomsma

    (VU Amsterdam)

Abstract

The methylome is subject to genetic and environmental effects. Their impact may depend on sex and age, resulting in sex- and age-related physiological variation and disease susceptibility. Here we estimate the total heritability of DNA methylation levels in whole blood and estimate the variance explained by common single nucleotide polymorphisms at 411,169 sites in 2,603 individuals from twin families, to establish a catalogue of between-individual variation in DNA methylation. Heritability estimates vary across the genome (mean=19%) and interaction analyses reveal thousands of sites with sex-specific heritability as well as sites where the environmental variance increases with age. Integration with previously published data illustrates the impact of genome and environment across the lifespan at methylation sites associated with metabolic traits, smoking and ageing. These findings demonstrate that our catalogue holds valuable information on locations in the genome where methylation variation between people may reflect disease-relevant environmental exposures or genetic variation.

Suggested Citation

  • Jenny van Dongen & Michel G. Nivard & Gonneke Willemsen & Jouke-Jan Hottenga & Quinta Helmer & Conor V. Dolan & Erik A. Ehli & Gareth E. Davies & Maarten van Iterson & Charles E. Breeze & Stephan Beck, 2016. "Genetic and environmental influences interact with age and sex in shaping the human methylome," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11115
    DOI: 10.1038/ncomms11115
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    Cited by:

    1. Fiona A. Hagenbeek & Jana S. Hirzinger & Sophie Breunig & Susanne Bruins & Dmitry V. Kuznetsov & Kirsten Schut & Veronika V. Odintsova & Dorret I. Boomsma, 2023. "Maximizing the value of twin studies in health and behaviour," Nature Human Behaviour, Nature, vol. 7(6), pages 849-860, June.
    2. Adrienne Tin & Pascal Schlosser & Pamela R. Matias-Garcia & Chris H. L. Thio & Roby Joehanes & Hongbo Liu & Zhi Yu & Antoine Weihs & Anselm Hoppmann & Franziska Grundner-Culemann & Josine L. Min & Vic, 2021. "Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus," Nature Communications, Nature, vol. 12(1), pages 1-18, December.

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