Portal de Periódicos da CAPES

Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-24824-z

2041-1723

Gita A. Pathak, Kritika Singh, Tyne W. Miller‐Fleming, Frank R. Wendt, Nava Ehsan, Kangcheng Hou, Ruth Johnson, Zeyun Lu, Shyamalika Gopalan, Loïc Yengo, Pejman Mohammadi, Bogdan Paşaniuc, Renato Polimanti, Lea K. Davis, Nicholas Mancuso,

Long-Term Effects of COVID-19

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.