Mendelian randomization analysis provides causality of smoking on the expression of ACE2, a putative SARS-CoV-2 receptor

eLife

Hui Liu¹  Xia Jiang²  Junyi Xin³  Sheng Cai⁴ 

[1] Biomedical Research Center, Zhejiang Provincial Key Laboratory of Laparoscopic Technology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China;Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden;Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China;Institute of Drug Metabolism and Pharmaceutical Analysis, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Zhejiang University, Hangzhou, China;

关键词: smoking status;    smoking intensity;    alcohol consumption;    ACE2 expression;    COVID-19 related adverse outcomes;    mendelian randomization;    Human;   

DOI  :  10.7554/eLife.64188

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 (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: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).

【 授权许可】

CC BY