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Bayesian reassessment of the epigenetic architecture of complex traits

Author

Listed:
  • Daniel Trejo Banos

    (University of Lausanne)

  • Daniel L. McCartney

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Marion Patxot

    (University of Lausanne)

  • Lucas Anchieri

    (University of Lausanne)

  • Thomas Battram

    (University of Bristol
    Bristol Medical School, University of Bristol)

  • Colette Christiansen

    (King’s College London)

  • Ricardo Costeira

    (King’s College London)

  • Rosie M. Walker

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Stewart W. Morris

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Archie Campbell

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Qian Zhang

    (University of Queensland)

  • David J. Porteous

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Allan F. McRae

    (University of Queensland)

  • Naomi R. Wray

    (University of Queensland)

  • Peter M. Visscher

    (University of Queensland)

  • Chris S. Haley

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Kathryn L. Evans

    (Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Ian J. Deary

    (University of Edinburgh
    University of Edinburgh)

  • Andrew M. McIntosh

    (Institute of Genetics and Molecular Medicine, University of Edinburgh
    University of Edinburgh
    University of Edinburgh, Royal Edinburgh Hospital)

  • Gibran Hemani

    (University of Bristol
    Bristol Medical School, University of Bristol)

  • Jordana T. Bell

    (King’s College London)

  • Riccardo E. Marioni

    (Institute of Genetics and Molecular Medicine, University of Edinburgh
    University of Edinburgh)

  • Matthew R. Robinson

    (Institute of Science and Technology Austria)

Abstract

Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal.

Suggested Citation

  • Daniel Trejo Banos & Daniel L. McCartney & Marion Patxot & Lucas Anchieri & Thomas Battram & Colette Christiansen & Ricardo Costeira & Rosie M. Walker & Stewart W. Morris & Archie Campbell & Qian Zhan, 2020. "Bayesian reassessment of the epigenetic architecture of complex traits," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16520-1
    DOI: 10.1038/s41467-020-16520-1
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    Cited by:

    1. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Thomas Battram & Tom R. Gaunt & Caroline L. Relton & Nicholas J. Timpson & Gibran Hemani, 2022. "A comparison of the genes and genesets identified by GWAS and EWAS of fifteen complex traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Marion Patxot & Daniel Trejo Banos & Athanasios Kousathanas & Etienne J. Orliac & Sven E. Ojavee & Gerhard Moser & Alexander Holloway & Julia Sidorenko & Zoltan Kutalik & Reedik Mägi & Peter M. Vissch, 2021. "Probabilistic inference of the genetic architecture underlying functional enrichment of complex traits," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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