COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types.
Benjamin J SchmiedelJob RochaCristian Gonzalez-ColinSourya BhattacharyyaAriel MadrigalChristian Hermann OttensmeierFerhat AyVivek ChandraPandurangan VijayanandPublished in: Nature communications (2021)
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.
Keyphrases
- coronavirus disease
- sars cov
- gene expression
- regulatory t cells
- genome wide
- copy number
- dna methylation
- dendritic cells
- respiratory syndrome coronavirus
- single cell
- oxidative stress
- transcription factor
- poor prognosis
- cell proliferation
- immune response
- peripheral blood
- risk assessment
- early onset
- binding protein
- genome wide identification