COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types
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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.
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SciScore for 10.1101/2020.12.01.407429: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The Institutional Review Board (IRB) of the La Jolla Institute for Allergy and Immunology (LJI; IRB protocol
Consent: For the DICE study, a total of 91 healthy volunteers were recruited in the San Diego area, who provided leukapheresis samples at the San Diego Blood Bank (SDBB) after written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Linkage disequilibrium (LD) for lead COVID-19-risk-variants was calculated using PLINK v1.90b3w25 for continental ‘super populations’ (AFR, AMR, EAS, EUR, SAS) based on data from the … SciScore for 10.1101/2020.12.01.407429: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The Institutional Review Board (IRB) of the La Jolla Institute for Allergy and Immunology (LJI; IRB protocol
Consent: For the DICE study, a total of 91 healthy volunteers were recruited in the San Diego area, who provided leukapheresis samples at the San Diego Blood Bank (SDBB) after written informed consent.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources Linkage disequilibrium (LD) for lead COVID-19-risk-variants was calculated using PLINK v1.90b3w25 for continental ‘super populations’ (AFR, AMR, EAS, EUR, SAS) based on data from the phase 3 of the 1,000 Genomes Project26. PLINKsuggested: (PLINK, RRID:SCR_001757)Results from OddPub: Thank you for sharing your code and data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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