Integrative genomic analyses identify susceptibility genes underlying COVID-19 hospitalization.
Gita A PathakKritika SinghTyne W Miller-FlemingFrank R WendtNava EhsanKangcheng HouRuth JohnsonZeyun LuShyamalika GopalanLoic YengoPejman MohammadiBogdan PasaniucRenato PolimantiLea K DavisNicholas MancusoPublished in: Nature communications (2021)
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.
Keyphrases
- coronavirus disease
- sars cov
- genome wide
- inflammatory response
- respiratory syndrome coronavirus
- bioinformatics analysis
- genome wide identification
- oxidative stress
- computed tomography
- gene expression
- stem cells
- dna methylation
- depressive symptoms
- magnetic resonance imaging
- physical activity
- lipopolysaccharide induced
- mesenchymal stem cells
- copy number
- cross sectional