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Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits

Author

Listed:
  • Shaza B. Zaghlool

    (Weill Cornell Medicine-Qatar
    Virginia Tech)

  • Brigitte Kühnel

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Mohamed A. Elhadad

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance)

  • Sara Kader

    (Weill Cornell Medicine-Qatar)

  • Anna Halama

    (Weill Cornell Medicine-Qatar)

  • Gaurav Thareja

    (Weill Cornell Medicine-Qatar)

  • Rudolf Engelke

    (Proteomics Core, Weill Cornell Medicine‐Qatar)

  • Hina Sarwath

    (Proteomics Core, Weill Cornell Medicine‐Qatar)

  • Eman K. Al-Dous

    (Genomics Core, Weill Cornell Medicine-Qatar)

  • Yasmin A. Mohamoud

    (Genomics Core, Weill Cornell Medicine-Qatar)

  • Thomas Meitinger

    (German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance
    Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Human Genetics, Technical University Munich)

  • Rory Wilson

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Konstantin Strauch

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich)

  • Annette Peters

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance)

  • Dennis O. Mook-Kanamori

    (Department of Clinical Epidemiology, Leiden University Medical Centre)

  • Johannes Graumann

    (Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute
    German Centre for Cardiovascular Research (DZHK), partner site Rhine-Main, Max Planck Institute of Heart and Lung Research)

  • Joel A. Malek

    (Genomics Core, Weill Cornell Medicine-Qatar)

  • Christian Gieger

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance)

  • Melanie Waldenberger

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance)

  • Karsten Suhre

    (Weill Cornell Medicine-Qatar)

Abstract

DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation.

Suggested Citation

  • Shaza B. Zaghlool & Brigitte Kühnel & Mohamed A. Elhadad & Sara Kader & Anna Halama & Gaurav Thareja & Rudolf Engelke & Hina Sarwath & Eman K. Al-Dous & Yasmin A. Mohamoud & Thomas Meitinger & Rory Wi, 2020. "Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13831-w
    DOI: 10.1038/s41467-019-13831-w
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    Cited by:

    1. Matthias Wielscher & Pooja R. Mandaviya & Brigitte Kuehnel & Roby Joehanes & Rima Mustafa & Oliver Robinson & Yan Zhang & Barbara Bodinier & Esther Walton & Pashupati P. Mishra & Pascal Schlosser & Ro, 2022. "DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. 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.

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