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Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

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

Nature communications, 2021-07, Vol.12 (1), p.4569-4569, Article 4569 [Periódico revisado por pares]

England: Nature Publishing Group

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Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization
Autor: Pathak, Gita A ; Singh, Kritika ; Miller-Fleming, Tyne W ; Wendt, Frank R ; Ehsan, Nava ; Hou, Kangcheng ; Johnson, Ruth ; Lu, Zeyun ; Gopalan, Shyamalika ; Yengo, Loic ; Mohammadi, Pejman ; Pasaniuc, Bogdan ; Polimanti, Renato ; Davis, Lea K ; Mancuso, Nicholas
Assuntos: Biobanks ; Biomarkers ; Coagulation ; Coronaviruses ; COVID-19 ; COVID-19 - genetics ; COVID-19 - metabolism ; Gene expression ; Genes ; Genetic Predisposition to Disease - genetics ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomic analysis ; Hospitalization ; Humans ; Inflammation ; Inflammatory response ; Polymorphism, Single Nucleotide - genetics ; Proteomes ; Risk Factors ; Severe acute respiratory syndrome coronavirus 2 ; Signs and symptoms ; Splicing ; Symptomology ; Transcriptomes ; Viral diseases
É parte de: Nature communications, 2021-07, Vol.12 (1), p.4569-4569, Article 4569
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SourceType-Scholarly Journals-1
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Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization

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

England: Nature Publishing Group

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