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Parent of origin genetic effects on methylation in humans are common and influence complex trait variation

Author

Listed:
  • Yanni Zeng

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

  • Carmen Amador

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

  • Charley Xia

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

  • Riccardo Marioni

    (University of Edinburgh
    University of Edinburgh)

  • Duncan Sproul

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

  • Rosie M. Walker

    (University of Edinburgh
    University of Edinburgh)

  • Stewart W. Morris

    (University of Edinburgh)

  • Andrew Bretherick

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

  • Oriol Canela-Xandri

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

  • Thibaud S. Boutin

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

  • David W. Clark

    (University of Edinburgh)

  • Archie Campbell

    (University of Edinburgh)

  • Konrad Rawlik

    (University of Edinburgh)

  • Caroline Hayward

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

  • Reka Nagy

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

  • Albert Tenesa

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

  • David J. Porteous

    (University of Edinburgh
    University of Edinburgh)

  • James F. Wilson

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

  • Ian J. Deary

    (University of Edinburgh
    University of Edinburgh)

  • Kathryn L. Evans

    (University of Edinburgh
    University of Edinburgh)

  • Andrew M. McIntosh

    (University of Edinburgh
    University of Edinburgh)

  • Pau Navarro

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

  • Chris S. Haley

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

Abstract

Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits.

Suggested Citation

  • Yanni Zeng & Carmen Amador & Charley Xia & Riccardo Marioni & Duncan Sproul & Rosie M. Walker & Stewart W. Morris & Andrew Bretherick & Oriol Canela-Xandri & Thibaud S. Boutin & David W. Clark & Archi, 2019. "Parent of origin genetic effects on methylation in humans are common and influence complex trait variation," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09301-y
    DOI: 10.1038/s41467-019-09301-y
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