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

Schmiedel, Benjamin J; Rocha, Job; Gonzalez-Colin, Cristian; Bhattacharyya, Sourya; Madrigal, Ariel; Ottensmeier, Christian H; Ay, Ferhat; Chandra, Vivek et al. · Nat Commun · 2021

basic_science · Level V

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Abstract

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<sub>H</sub>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.

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