Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study
Shuai Li, Xinyang Hua
BMC Medical Genomics, doi:10.1186/s12920-021-00887-1
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.
Supplementary Information The online version contains supplementary material available at https ://doi. org/10.1186/s1292 0-021-00887 -1. Additional file 1: Supplementary Tables 1-4 . Summary statistics for genetic instrumental variables of the four lifestyle factors. Additional file 2: Supplementary Table 5 . Parameter values used in statistical power analysis. Additional file 3: Supplementary Table 6 . Sample sizes of participating studies in the COVID-19 Host Genetic Initiative GWAS Release 4 in September 2020. Additional file 4: Supplementary Fig. 1 . Leave-one-out analysis results for body mass index and severe respiratory COVID-19. Additional file 5: Supplementary Fig. 2 . Leave-one-out analysis results for body mass index and COVID-19 hospitalization. Additional file 6: Supplementary Fig. 3 . Leave-one-out analysis results for lifetime smoking and severe respiratory COVID-19. Additional file 7: Supplementary Fig. 4 . Leave-one-out analysis results for lifetime smoking and COVID-19 hospitalization. Additional file 8: Supplementary Fig. 5 . Leave-one-out analysis results for physical activity and severe respiratory COVID-19. Additional file 9: Supplementary Fig. 6 . Leave-one-out analysis results for physical activity and COVID-19 hospitalization. Additional file 10: Supplementary Fig. 7 . Leave-one-out analysis results for alcohol consumption and severe respiratory COVID-19 using all genetic variants. Additional file 11: Supplementary Fig. 8 . Leave-one-out..
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