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- Title
The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study.
- Authors
Butler-Laporte, Guillaume; Nakanishi, Tomoko; Mooser, Vincent; Renieri, Alessandra; Amitrano, Sara; Zhou, Sirui; Chen, Yiheng; Forgetta, Vincenzo; Richards, J Brent
- Abstract
<bold>Background: </bold>There has been uncertainty about the safety or benefit of angiotensin-converting enzyme (ACE) inhibitors during the COVID-19 pandemic. We used Mendelian randomization using genetic determinants of serum-ACE levels to test whether decreased ACE levels increase susceptibility to SARS-CoV-2 infection or COVID-19 severity, while reducing potential bias from confounding and reverse causation in observational studies.<bold>Methods: </bold>Genetic variants strongly associated with ACE levels, which were nearby the ACE gene, were identified from the ORIGIN trial and a separate genome-wide association study (GWAS) of ACE levels from the AGES cohort. The ORIGIN trial included 4147 individuals of European and Latino ancestries. Sensitivity analyses were performed using a study of 3200 Icelanders. Cohorts from the COVID-19 Host Genetics Initiative GWAS of up to 960 186 individuals of European ancestry were used for COVID-19 susceptibility, hospitalization and severe-disease outcome.<bold>Results: </bold>Genetic variants were identified that explain between 18% and 37% of variance in ACE levels. Using genetic variants from the ORIGIN trial, a standard-deviation decrease in ACE levels was not associated with an increase in COVID-19 susceptibility [odds ratio (OR): 1.02, 95% confidence interval (CI): 0.90, 1.15], hospitalization (OR: 0.86, 95% CI: 0.68, 1.08) or severe disease (OR: 0.74, 95% CI: 0.51, 1.06). Using genetic variants from the AGES cohort, the result was similar for susceptibility (OR: 0.98, 95% CI: 0.89, 1.09), hospitalization (OR: 0.86, 95% CI: 0.66, 1.11) and severity (OR: 0.75, 95% CI: 0.50, 1.14). Multiple-sensitivity analyses led to similar results.<bold>Conclusion: </bold>Genetically decreased serum ACE levels were not associated with susceptibility to, or severity of, COVID-19 disease. These data suggest that individuals taking ACE inhibitors should not discontinue therapy during the COVID-19 pandemic.
- Subjects
COVID-19; COVID-19 pandemic; ANGIOTENSIN converting enzyme; COVID-19 treatment; SARS-CoV-2; ACE inhibitors; RESEARCH funding; ICELANDERS
- Publication
International Journal of Epidemiology, 2021, Vol 50, Issue 1, p75
- ISSN
0300-5771
- Publication type
journal article
- DOI
10.1093/ije/dyaa229