Mendelian randomization analysis provides causality of smoking on the expression of ACE2, a putative SARS-CoV-2 receptor.
Elife
; 102021 07 06.
Article
in English
| MEDLINE | ID: covidwho-1298242
ABSTRACT
Background:
To understand a causal role of modifiable lifestyle factors in angiotensin-converting enzyme 2 (ACE2) expression (a putative severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) across 44 human tissues/organs, and in coronavirus disease 2019 (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 pleiotropy residual sum and outlier (MR-PRESSO) were performed to identify potential horizontal pleiotropy.Results:
We found that genetically predicted smoking intensity significantly increased ACE2 expression in thyroid (ß=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:
XJ 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).Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Mendelian Randomization Analysis
/
Tobacco Smoking
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Variants
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
ELife.64188
Similar
MEDLINE
...
LILACS
LIS