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Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

Author

Listed:
  • Gita A. Pathak

    (Division of Human Genetics
    Veteran Affairs Connecticut Healthcare System)

  • Kritika Singh

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Tyne W. Miller-Fleming

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Frank R. Wendt

    (Division of Human Genetics
    Veteran Affairs Connecticut Healthcare System)

  • Nava Ehsan

    (The Scripps Research Institute)

  • Kangcheng Hou

    (University of California Los Angeles)

  • Ruth Johnson

    (University of California Los Angeles)

  • Zeyun Lu

    (University of Southern California)

  • Shyamalika Gopalan

    (University of Southern California)

  • Loic Yengo

    (The University of Queensland)

  • Pejman Mohammadi

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Bogdan Pasaniuc

    (University of California Los Angeles)

  • Renato Polimanti

    (Division of Human Genetics
    Veteran Affairs Connecticut Healthcare System)

  • Lea K. Davis

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Nicholas Mancuso

    (University of Southern California
    University of Southern California)

Abstract

Despite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of genes and pathways that contribute to COVID-19. Here, we integrate a genome-wide association study of COVID-19 hospitalization (7,885 cases and 961,804 controls from COVID-19 Host Genetics Initiative) with mRNA expression, splicing, and protein levels (n = 18,502). We identify 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. We functionally characterize the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (n = 85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicate these findings across trans-ethnic studies and observed consistent effects in individuals of diverse ancestral backgrounds in Vanderbilt Biobank, pan-UK Biobank, and Biobank Japan. Our study highlights and reconfirms putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.

Suggested Citation

  • Gita A. Pathak & Kritika Singh & Tyne W. Miller-Fleming & Frank R. Wendt & Nava Ehsan & Kangcheng Hou & Ruth Johnson & Zeyun Lu & Shyamalika Gopalan & Loic Yengo & Pejman Mohammadi & Bogdan Pasaniuc &, 2021. "Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24824-z
    DOI: 10.1038/s41467-021-24824-z
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    Cited by:

    1. Maik Pietzner & Robert Lorenz Chua & Eleanor Wheeler & Katharina Jechow & Julian D. S. Willett & Helena Radbruch & Saskia Trump & Bettina Heidecker & Hugo Zeberg & Frank L. Heppner & Roland Eils & Mar, 2022. "ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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