Genetic risk factors for death with SARS-CoV-2 from the UK Biobank
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Abstract
We present here genetic risk factors for survivability from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 19 (COVID-19). At the time of writing it is too early to determine comprehensively and without doubt all risk factors, but there is an urgency due to the global pandemic crisis that merits this early analysis. We have nonetheless discovered 5 novel risk variants in 4 genes, discovered by examining 193 deaths from 1,412 confirmed infections in a group of 5,871 UK Biobank participants tested for the virus. We also examine the distribution of these genetic variants across broad ethnic groups and compare it to data from the UK Office of National Statistics for increased risk of death from SARS-CoV-2. We confidently identify the gene ERAP2 with a high-risk variant, as well as three other genes of potential interest. Although mostly rare, a common theme of genetic risk factors affecting survival might be the inability to launch or modulate an effective immune and stress response to infection from the SARS-CoV-2 virus.
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SciScore for 10.1101/2020.07.01.20144592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 These were subjected to data quality Control using Plink software 46. Plinksuggested: (PLINK, RRID:SCR_001757)From the predicted phenotypes in the UK Biobank cohort participants who were tested for SARS-CoV- 2, potentially causal genes were obtained from the ontology via the dcGO mapping, comprising of: ALOXE3, BRF2, ERAP2, MPP5, RAMP3, RBL1 and TMEM181. dcGOsuggested: (dcGO, RRID:SCR_014392)Independently of this, we used a separate list of potentially causal genes that was … SciScore for 10.1101/2020.07.01.20144592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. 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 These were subjected to data quality Control using Plink software 46. Plinksuggested: (PLINK, RRID:SCR_001757)From the predicted phenotypes in the UK Biobank cohort participants who were tested for SARS-CoV- 2, potentially causal genes were obtained from the ontology via the dcGO mapping, comprising of: ALOXE3, BRF2, ERAP2, MPP5, RAMP3, RBL1 and TMEM181. dcGOsuggested: (dcGO, RRID:SCR_014392)Independently of this, we used a separate list of potentially causal genes that was created by the UniProt 50 database team, and annotated by them as SARS-CoV-2 receptors comprising: ACE2, BSG, BST2, FURIN, IL6, IL6R, IL6ST, ITGAL, UniProtsuggested: (UniProtKB, RRID:SCR_004426)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 6 and 14. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
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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SciScore for 10.1101/2020.07.01.20144592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable We also observed that all 5 of the deaths in people with this variant were in men who self-reported as having hypertension; of the 6 survivors 4 are female and 2 male ( one with hypertension) . Table 2: Resources
Software and Algorithms Sentences Resources These were subjected to data quality Control using Plink software 46 . Plinksuggested: (PLINK, SCR_001757)We used a method of phenotype prediction 49 which combines ontologies from dcGO and the same principles of HMM dirichlet … SciScore for 10.1101/2020.07.01.20144592: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable We also observed that all 5 of the deaths in people with this variant were in men who self-reported as having hypertension; of the 6 survivors 4 are female and 2 male ( one with hypertension) . Table 2: Resources
Software and Algorithms Sentences Resources These were subjected to data quality Control using Plink software 46 . Plinksuggested: (PLINK, SCR_001757)We used a method of phenotype prediction 49 which combines ontologies from dcGO and the same principles of HMM dirichlet mixtures as used by FATHMM , against a genetic background from the 1000 genomes project . dcGOsuggested: (dcGO, SCR_014392)Independently of this , we used a separate list of potentially causal genes that was created by the UniProt 50 database team , and annotated by them as SARS-CoV-2 receptors comprising: ACE2 , BSG , BST2 , FURIN , IL6 , IL6R , IL6ST , ITGAL , UniProtsuggested: (UniProtKB, SCR_004426)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 OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).
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