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Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health

Author

Listed:
  • Danni A. Gadd

    (University of Edinburgh)

  • Robert F. Hillary

    (University of Edinburgh)

  • Daniel L. McCartney

    (University of Edinburgh)

  • Liu Shi

    (University of Oxford)

  • Aleks Stolicyn

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Neil A. Robertson

    (University of Edinburgh)

  • Rosie M. Walker

    (Centre for Clinical Brain Sciences, Chancellor’s Building)

  • Robert I. McGeachan

    (University of Edinburgh
    The University of Edinburgh)

  • Archie Campbell

    (University of Edinburgh)

  • Shen Xueyi

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Miruna C. Barbu

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Claire Green

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Stewart W. Morris

    (University of Edinburgh)

  • Mathew A. Harris

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Ellen V. Backhouse

    (Centre for Clinical Brain Sciences, Chancellor’s Building)

  • Joanna M. Wardlaw

    (Centre for Clinical Brain Sciences, Chancellor’s Building
    University of Edinburgh
    University of Edinburgh)

  • J. Douglas Steele

    (University of Dundee)

  • Diego A. Oyarzún

    (University of Edinburgh
    University of Edinburgh
    The Alan Turing Institute)

  • Graciela Muniz-Terrera

    (University of Edinburgh
    Ohio University)

  • Craig Ritchie

    (University of Edinburgh)

  • Alejo Nevado-Holgado

    (University of Oxford)

  • Tamir Chandra

    (University of Edinburgh)

  • Caroline Hayward

    (University of Edinburgh
    University of Edinburgh)

  • Kathryn L. Evans

    (University of Edinburgh)

  • David J. Porteous

    (University of Edinburgh)

  • Simon R. Cox

    (University of Edinburgh
    University of Edinburgh)

  • Heather C. Whalley

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Andrew M. McIntosh

    (University of Edinburgh, Royal Edinburgh Hospital)

  • Riccardo E. Marioni

    (University of Edinburgh)

Abstract

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.

Suggested Citation

  • Danni A. Gadd & Robert F. Hillary & Daniel L. McCartney & Liu Shi & Aleks Stolicyn & Neil A. Robertson & Rosie M. Walker & Robert I. McGeachan & Archie Campbell & Shen Xueyi & Miruna C. Barbu & Claire, 2022. "Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32319-8
    DOI: 10.1038/s41467-022-32319-8
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