Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus
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Abstract
To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify SLC6A20 and CXCR6 as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between correlational and causal studies of human biology.
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SciScore for 10.1101/2021.04.09.21255184: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources After transduction and selection for the GeCKOv2 library (maintaining ∼1000-fold library representation), we infected 125 million A549ACE2 cells with SARS-CoV-2 virus (NIAID BEI isolate USA-WA1/2020) at two multiplicity of infections (MOIs): 0.01 (low MOI) and 0.3 (high MOI), which differ by the amount of virus used to infect the cells. A549ACE2suggested: NoneSoftware and Algorithms Sentences Resources We aligned trimmed sequencing reads to the GeCKOv2 reference using bowtie v1.1.2 [-a -- best --strata -v 1 –norc] allowing 1 nucleotide mismatch to determine the read counts per guide. …SciScore for 10.1101/2021.04.09.21255184: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources After transduction and selection for the GeCKOv2 library (maintaining ∼1000-fold library representation), we infected 125 million A549ACE2 cells with SARS-CoV-2 virus (NIAID BEI isolate USA-WA1/2020) at two multiplicity of infections (MOIs): 0.01 (low MOI) and 0.3 (high MOI), which differ by the amount of virus used to infect the cells. A549ACE2suggested: NoneSoftware and Algorithms Sentences Resources We aligned trimmed sequencing reads to the GeCKOv2 reference using bowtie v1.1.2 [-a -- best --strata -v 1 –norc] allowing 1 nucleotide mismatch to determine the read counts per guide. bowtiesuggested: (Bowtie, RRID:SCR_005476)For plotting data for COVID-19 GWAS and eQTLs from the eQTL Catalogue, we used genotype data from the 1000 Genomes Project, and calculated weighted average r2 value based on the counts of global ancestral populations in the analysis (if multiple global ancestry populations were studied). 1000 Genomes Projectsuggested: (1000 Genomes Project and AWS, RRID:SCR_008801)Results from OddPub: Thank you for sharing your 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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