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).
【저자키워드】 alcohol consumption, mendelian randomization, Human, smoking status, smoking intensity, ACE2 expression, COVID-19 related adverse outcomes, 【초록키워드】 COVID-19, coronavirus disease, Coronavirus disease 2019, ACE2, coronavirus, alcohol consumption, susceptibility, severity, smoking, alcohol, angiotensin-converting enzyme 2, Brain, Research, Genetic variant, receptor, Thyroid, respiratory, ACE2 expression, Pleiotropy, expression, liver, predict, funding, association, Angiotensin-converting enzyme, angiotensin, Odds ratio, life, intensity, instrumental variables, Colon, acute respiratory syndrome, Factor, horizontal pleiotropy, working, Welfare, MR-PRESSO, phenome, outlier, MR-Egger regression, weighted median, adipose, Council, approach, risk of COVID-19, instrumental variable, significantly increased, predicted, identify, performed, conducted, supported, were used, adopted, Swedish, statistically significant, 【제목키워드】 ACE2, SARS-CoV-2 receptor, expression, Analysis, provide,