Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

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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.

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Pathak, G. A., Singh, K., Miller-Fleming, T. W., Wendt, F. R., Ehsan, N., Hou, K., … Mancuso, N. (2021). Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-24824-z

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