Background: To understand a causal role of modifiable lifestyle factors in ACE2 expression (a putative SARS-CoV-2 receptor) across 44 human tissues/organs, and in COVID-19 susceptibility and severity, we conducted a phenome-wide two-sample Mendelian randomization (MR) study.
Methods: More than 500 genetic variants were used as instrumental variables to predict smoking and alcohol consumption. Inverse-variance weighted approach was adopted as the primary method to estimate a causal association, while MR-Egger regression, weighted median and MR-PRESSO were performed to identify potential horizontal pleiotropy.
Results: We found that genetically predicted smoking intensity significantly increased ACE2 expression in thyroid (β=1.468, p=1.8 10-8); and increased ACE2 expression in adipose, brain, colon and liver with nominal significance. Additionally, genetically predicted smoking initiation significantly increased the risk of COVID-19 onset (odds ratio=1.14, p=8.7 10-5). No statistically significant result was observed for alcohol consumption.
Conclusions: Our work demonstrates an important role of smoking, measured by both status and intensity, in the susceptibility to COVID-19.
Funding: Dr. Jiang is supported by research grants from the Swedish Research Council (VR-2018-02247) and Swedish Research Council for Health, Working Life and Welfare (FORTE-2020-00884).
Data and main programming codes with annotations have been uploaded to GitHub and made publicly available at https://github.com/hye-hz/MR_Smoke_COVID19.git.
Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol usedoi: 10.1038/s41588-018-0307-5.
Genetic effects on gene expression across human tissuesdoi: 10.1038/nature24277.
COVID-19 Host Genetics Initiativedoi: 10.1038/s41431-020-0636-6.
- Xia Jiang
- Xia Jiang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- M Dawn Teare, Newcastle University, United Kingdom
© 2021, Liu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.