Abstract

BackgroundLifestyle 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.MethodsGenome-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.ResultsBoth 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.ConclusionsEvidence 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.

Highlights

  • Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death

  • Both genetically predicted body mass index (BMI) and lifetime smoking were found to be associated with increased risk of COVID-19 severe illness: the per-standard deviation (SD) Odds ratio (OR) of genetically predicted BMI was 1.91 (95% confidence interval [Confidence interval (CI)], 1.55, 2.35, P = 7.4 × 10–10) for severe respiratory COVID-19 and 1.75 for COVID-19 hospitalization; the per-SD OR of genetically predicted lifetime smoking was 1.84 for severe respiratory COVID-19 and 2.15 for COVID-19 hospitalization

  • No evidence of association was found for genetically predicted alcohol consumption with severe respiratory COVID-19 or COVID-19 hospitalization

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Summary

Introduction

Lifestyle factors including obesity and smoking are suggested to be correlated with increased risk of COVID-19 severe illness or related death. 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. Studies have reported the correlations between obesity and severe illness or related death of COVID-19 [1,2,3]. Mendelian randomisation (MR) uses exposure-associated genetic variants as instrumental variables to assess the causality between exposures and outcomes [9]. The publicly available genome-wide association studies (GWAS) summary statistics provide valuable resources for assessing the causality between lifestyle factors and the risk of COVID-19 severe illness

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