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

Schmiedel, Benjamin J, Chandra, Vivek, Rocha, Job, Gonzalez-Colin, Cristian, Bhattacharyya, Sourya, Madrigal, Ariel, Ottensmeier, Christian H ORCID: 0000-0003-3619-1657, Ay, Ferhat and Vijayanand, Pandurangan (2020) COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types. [Preprint]

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Official URL: http://dx.doi.org/10.1101/2020.12.01.407429

Abstract

Common genetic polymorphisms associated with severity of COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Here, we assessed the effects of 679 COVID-19-risk variants on gene expression in a wide-range of immune cell types. Severe COVID-19-risk variants were significantly associated with the expression of 11 protein-coding genes, and overlapped with either target gene promoter or cis -regulatory regions that interact with target promoters in the cell types where their effects are most prominent. For example, we identified that the association between variants in the 3p21.31 risk locus and the expression of CCR2 in classical monocytes is likely mediated through an active cis-regulatory region that interacted with CCR2 promoter specifically in monocytes. The expression of several other genes showed prominent genotype-dependent effects in non-classical monocytes, NK cells, B cells, or specific T cell subtypes, highlighting the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.

Item Type:	Preprint
Uncontrolled Keywords:	Neurodegenerative, Genetics, Human Genome, Genetic Testing, Prevention, 2.1 Biological and endogenous factors, 2 Aetiology, 3 Good Health and Well Being
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	23 Dec 2021 08:05
Last Modified:	15 Mar 2024 17:19
DOI:	10.1101/2020.12.01.407429
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3145884