Common genetic polymorphisms associated with COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Given the importance of immune cells in the pathogenesis of COVID-19 illness, here we assessed the effects of COVID-19-risk variants on gene expression in a wide range of immune cell types. Transcriptome-wide association study and colocalization analysis revealed putative causal genes and the specific immune cell types where gene expression is most influenced by COVID-19-risk variants. Notable examples include OAS1 in non-classical monocytes, DTX1 in B cells, IL10RB in NK cells, CXCR6 in follicular helper T cells, CCR9 in regulatory T cells and ARL17A in T H 2 cells. By analysis of transposase accessible chromatin and H3K27ac-based chromatin-interaction maps of immune cell types, we prioritized potentially functional COVID-19-risk variants. Our study highlights the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations. Immune cells are important in the pathogenesis of COVID-19. Here the authors assessed the effects of COVID-19-risk variants on gene expression in a range of immune cell types, highlighting their potential to impact the function of diverse immune cell types and influence severe disease.
【저자키워드】 viral infection, Risk factors, Immunogenetics, 【초록키워드】 COVID-19, Monocytes, Pathogenesis, Gene Expression, OAS1, T cells, variant, B cells, NK cells, variants, Non-classical monocytes, Regulatory T cell, cells, pathway, immune cells, molecular, regulatory T cells, association, helper T cells, Analysis, Genetic polymorphism, Immune cell, IL10RB, severe disease, CXCR6, genetic risk, cell types, cell type, disease pathogenesis, COVID-19 illness, pathogenesis of COVID-19, severe disease manifestations, transposase, immune cell types, chromatin, H3K27ac, driving, ARL17A, CCR9, DTX1, Effect, Cell, highlight, common, example, include, functional, highlighting, follicular, immune cell type, with COVID-19, 【제목키워드】 COVID-19, variant, expression, genetic risk, immune cell type,