Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

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, Renato Polimanti, Lea K. Davis and Nicholas Mancuso ()
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Gita A. Pathak: Division of Human Genetics
Kritika Singh: Vanderbilt University Medical Center
Tyne W. Miller-Fleming: Vanderbilt University Medical Center
Frank R. Wendt: Division of Human Genetics
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
Bogdan Pasaniuc: University of California Los Angeles
Renato Polimanti: Division of Human Genetics
Lea K. Davis: Vanderbilt University Medical Center
Nicholas Mancuso: University of Southern California

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-24824-z

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