COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types

• Published in: Nature communications 2021-11, Vol.12 (1), p.6760-6760, Article 6760
• Main Authors: Schmiedel, Benjamin J., Rocha, Job, Gonzalez-Colin, Cristian, Bhattacharyya, Sourya, Madrigal, Ariel, Ottensmeier, Christian H., Ay, Ferhat, Chandra, Vivek, Vijayanand, Pandurangan
• Format: Article
• Language: English
• Subjects: 38/15; 38/39; 38/43; 38/91; 49/39; 631/250/2502/248; 631/250/255/2514; 692/499; CCR9 protein; Chromatin; Coronaviruses; COVID-19; COVID-19 - genetics; COVID-19 - immunology; Gene expression; Gene mapping; Gene polymorphism; Genes; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Health risk assessment; Helper cells; Humanities and Social Sciences; Humans; Illnesses; Immune system; Immunoregulation; Interleukin 1; Lymphocytes; Lymphocytes B; Lymphocytes T; Monocytes; multidisciplinary; Pathogenesis; Receptors, CCR - genetics; Receptors, CCR - metabolism; Risk; Risk Factors; Science; Science (multidisciplinary); T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Transcriptomes; Transposase; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-26888-3

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.