The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study. (8th December 2020)

• Record Type: Journal Article
• Authors: Butler-Laporte, Guillaume; Nakanishi, Tomoko; Mooser, Vincent; Renieri, Alessandra; Amitrano, Sara; Zhou, Sirui; Chen, Yiheng; Forgetta, Vincenzo; Richards, J Brent
• Is Part Of: International journal of epidemiology. Volume 50:Number 1(2021)
• Page Start: 75
• Page End: 86
• Publication Date: 2020-12-08
• Subjects: COVID-19 -- angiotensin-converting enzyme -- ACE inhibitors -- Mendelian randomization; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyaa229
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Background: 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. Methods: 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. Results: 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. Conclusion: 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.