Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis
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Abstract
The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity, host genetics may also be important. Identifying host-specific genetic factors indicate biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-COV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprising up to 49,562 COVID-19 patients from 46 studies across 19 countries worldwide. We reported 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. We further identified smoking and body mass index as causal risk factors for severe COVID-19. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was enabled by prioritization of shared resources and analytical frameworks. This working model of international collaboration provides a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease.
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SciScore for 10.1101/2021.03.10.21252820: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All subjects were recruited following protocols approved by local Institutional Review Boards (IRBs).
Consent: All protocols followed local ethics recommendations and informed consent was obtained when required.Randomization not detected. Blinding not detected. Power Analysis The MR-PRESSO Global test was shown to perform well when the outcome and exposure GWASs are not disjoint (although the power to detect horizontal pleiotropy is slightly reduced by complete sample overlap). Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We used a strict r2 threshold of 0.001, a 10MB clumping window, and the European … SciScore for 10.1101/2021.03.10.21252820: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: All subjects were recruited following protocols approved by local Institutional Review Boards (IRBs).
Consent: All protocols followed local ethics recommendations and informed consent was obtained when required.Randomization not detected. Blinding not detected. Power Analysis The MR-PRESSO Global test was shown to perform well when the outcome and exposure GWASs are not disjoint (although the power to detect horizontal pleiotropy is slightly reduced by complete sample overlap). Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources We used a strict r2 threshold of 0.001, a 10MB clumping window, and the European reference panel from the 1000 Genomes project 65 to discard SNPs in linkage disequilibrium with another variant with smaller p-value association. 1000 Genomessuggested: (1000 Genomes Project and AWS, RRID:SCR_008801)For genetic variants that were not present in the hospitalized COVID analysis, PLINK was used to identify proxy variants that were in LD (r2 > 0.8). PLINKsuggested: (PLINK, RRID:SCR_001757)Results from OddPub: Thank you for sharing your code.
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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