The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study.
Int J Epidemiol
; 50(1): 75-86, 2021 03 03.
Article
in English
| MEDLINE | ID: covidwho-990694
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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, Virus
/
Angiotensin-Converting Enzyme Inhibitors
/
Cardiovascular Diseases
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
/
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Female
/
Humans
/
Male
Language:
English
Journal:
Int J Epidemiol
Year:
2021
Document Type:
Article
Affiliation country:
Ije
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