Association of 25 hydroxyvitamin D concentration with risk of COVID-19: a Mendelian randomization study
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Abstract
Background
In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal.
Methods
We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs).
Results
MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (OR=1.168, 95% CI 0.956-1.427; OR=0.889, 95% CI 0.549-1.439). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed.
Conclusion
The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.
Article activity feed
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SciScore for 10.1101/2020.08.09.20171280: (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 In terms of various estimates for different measures, we chose the result of main MR method as the following rules: All data analyses were performed by the “twosampleMR” package using R version 4.0.0 (https://www.r-project.org/). https://www.r-project.org/suggested: (R Project for Statistical Computing, RRID:SCR_001905)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).
SciScore for 10.1101/2020.08.09.20171280: (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 In terms of various estimates for different measures, we chose the result of main MR method as the following rules: All data analyses were performed by the “twosampleMR” package using R version 4.0.0 (https://www.r-project.org/). https://www.r-project.org/suggested: (R Project for Statistical Computing, RRID:SCR_001905)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: We detected the following sentences addressing limitations in the study:Some limitations should be noticed. It is important to note that the results of the MR analyses are based on numerous assumptions. First, we selected genetic variants as IVs based on the recent large-scale GWAS 23, which showed a strong association with 25OHD concentration; therefore, the bias of weak instrument might be less likely. Second, the genetic variants are not associated with measured and unmeasured confounders that influence both vitamin D and COVID-19. However, the unmeasured confounders or alternative causal pathways may be still affected our results because of the limitation of the method. Third, the existence of horizontal pleiotropy may distort MR results. In our study, there was limited evidence of heterogeneity and horizontal pleiotropy. In addition, the GWAS of the severe COVID-19 cases included small sample size, which might lead to small effect for the MR estimate and limit the IVs for COVID-19 for reverse MR analysis. The findings were based on European population, which made it difficult to represent the universal conclusions for other ethnic groups. Therefore, the future studies with larger sample size and more ethnic groups are needed to verify and explore the observed associations.
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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