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Integrative analyses identify genes and their functional consequences underlying COVID-19 hospitalization
Molecular Genetics and Metabolism ; 132:S215, 2021.
Article in English | EMBASE | ID: covidwho-1735096
ABSTRACT
Recent emergence of SARS-Cov-2 has resulted in unprecedented spread of COVID-19 exhibiting wide variability in individuals’ symptoms. Despite rapid progress in characterizing the role of host genetics in SARS-Cov-2 infection, there is limited understanding of the role of host genetic variation and the molecular mechanisms including the knowledge of genes and pathways that contribute to COVID-19. Previous research to understand the mechanisms underlying severe COVID-19 outcomes have focused on lung- and brain-related pathologies. Here, we integrated 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 identified 27 genes related to inflammation and coagulation pathways whose genetically predicted expression was associated with COVID-19 hospitalization. These genes converge on cytokine-cytokine and the JAK-STAT signaling pathways. We functionally characterized the 27 genes using phenome- and laboratory-wide association scans in Vanderbilt Biobank (BioVU;n = 85,460) and identified coagulation-related clinical symptoms, immunologic, and blood-cell-related biomarkers. We replicated these findings in the African-American cohort here in BioVU and found concordant results. This study highlights putative causal genes impacting COVID-19 severity and symptomology through the host inflammatory response.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Molecular Genetics and Metabolism Year: 2021 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Language: English Journal: Molecular Genetics and Metabolism Year: 2021 Document Type: Article