Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study
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Abstract
Background
Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death. However, whether these relationships are causal is not well known; neither for the relationships between COVID-19 severe illness and other common lifestyle factors, such as physical activity and alcohol consumption.
Methods
Genome-wide significant genetic variants associated with body mass index (BMI), lifetime smoking, physical activity and alcohol consumption identified by large-scale genome-wide association studies (GWAS) of up to 941,280 individuals were selected as instrumental variables. Summary statistics of the genetic variants on severe illness of COVID-19 were obtained from GWAS analyses of up to 6492 cases and 1,012,809 controls. Two-sample Mendelian randomisation analyses were conducted.
Results
Both per-standard deviation (SD) increase in genetically predicted BMI and lifetime smoking were associated with about two-fold increased risks of severe respiratory COVID-19 and COVID-19 hospitalization (all P < 0.05). Per-SD increase in genetically predicted physical activity was associated with decreased risks of severe respiratory COVID-19 (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.05, 0.74; P = 0.02), but not with COVID-19 hospitalization (OR = 0.44; 95% CI 0.18, 1.07; P = 0.07). No evidence of association was found for genetically predicted alcohol consumption. Similar results were found across robust Mendelian randomisation methods.
Conclusions
Evidence is found that BMI and smoking causally increase and physical activity might causally decrease the risk of COVID-19 severe illness. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness and its public health value in fighting against COVID-19 pandemic.
Article activity feed
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SciScore for 10.1101/2020.10.19.20215525: (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 Statistical analyses: The statistical power was calculated using the proportion of variation in the lifestyle risk factor explained by the genetic instrumental variables, sample size of the COVID-19 GWAS, and the method proposed by Burgess15. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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 …SciScore for 10.1101/2020.10.19.20215525: (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 Statistical analyses: The statistical power was calculated using the proportion of variation in the lifestyle risk factor explained by the genetic instrumental variables, sample size of the COVID-19 GWAS, and the method proposed by Burgess15. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
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:Limitations of this study included that there might be bias in the causal effect estimates, as there was sample overlap between the lifestyle factors GWAS and COVID-19 GWAS, e.g., UK biobank participants were included in the GWAS of COVID-19 hospitalization. However, given the proportions of COVID-19 cases in the GWAS analyses were low, any bias must be minimal22. In conclusion, this study finds evidence that BMI and smoking causally increase and physical activity causally decreases the risk of COVID-19 severe illness. All these lifestyle risk factors are modifiable, so they could be targeted to reduce severe illness of COVID-19. This study highlights the importance of maintaining a healthy lifestyle in protecting from COVID-19 severe illness. The findings also have a profound public health value – a healthy lifestyle could be helpful for fighting against the COVID-19 pandemic.
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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