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COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types

Author

Listed:
  • Benjamin J. Schmiedel

    (La Jolla Institute for Immunology)

  • Job Rocha

    (La Jolla Institute for Immunology
    National Autonomous University of Mexico, Cuernavaca)

  • Cristian Gonzalez-Colin

    (La Jolla Institute for Immunology
    National Autonomous University of Mexico, Cuernavaca)

  • Sourya Bhattacharyya

    (La Jolla Institute for Immunology)

  • Ariel Madrigal

    (La Jolla Institute for Immunology)

  • Christian H. Ottensmeier

    (La Jolla Institute for Immunology
    University of Liverpool)

  • Ferhat Ay

    (La Jolla Institute for Immunology
    University of California San Diego)

  • Vivek Chandra

    (La Jolla Institute for Immunology)

  • Pandurangan Vijayanand

    (La Jolla Institute for Immunology
    University of Liverpool
    University of California San Diego)

Abstract

Common genetic polymorphisms associated with COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Given the importance of immune cells in the pathogenesis of COVID-19 illness, here we assessed the effects of COVID-19-risk variants on gene expression in a wide range of immune cell types. Transcriptome-wide association study and colocalization analysis revealed putative causal genes and the specific immune cell types where gene expression is most influenced by COVID-19-risk variants. Notable examples include OAS1 in non-classical monocytes, DTX1 in B cells, IL10RB in NK cells, CXCR6 in follicular helper T cells, CCR9 in regulatory T cells and ARL17A in TH2 cells. By analysis of transposase accessible chromatin and H3K27ac-based chromatin-interaction maps of immune cell types, we prioritized potentially functional COVID-19-risk variants. Our study highlights the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.

Suggested Citation

  • Benjamin J. Schmiedel & Job Rocha & Cristian Gonzalez-Colin & Sourya Bhattacharyya & Ariel Madrigal & Christian H. Ottensmeier & Ferhat Ay & Vivek Chandra & Pandurangan Vijayanand, 2021. "COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26888-3
    DOI: 10.1038/s41467-021-26888-3
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