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

Nat Commun. 2021 Nov 19;12(1):6760. 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 TH2 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • COVID-19 / genetics*
  • COVID-19 / immunology
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study
  • Humans
  • Receptors, CCR / genetics
  • Receptors, CCR / metabolism
  • Risk Factors
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism


  • CC chemokine receptor 9
  • Receptors, CCR