| Title: | The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study |
| Journal: | International Journal of Epidemiology |
| Published: | 8 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33349849/ |
| DOI: | https://doi.org/10.1093/ije/dyaa229 |
| URL: | https://academic.oup.com/ije/article-pdf/50/1/75/36449363/dyaa229.pdf |
| Citations: | 12 (3 in last 2 years) as of 8 Aug 2024 |
Publication 12889
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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.</p>
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.</p>
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.</p>
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.</p>
15 Keywords
- Angiotensin-Converting Enzyme 2
- Angiotensin-Converting Enzyme Inhibitors
- COVID-19
- COVID-19 Drug Treatment
- Cardiovascular Diseases
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Pandemics
- Receptors, Virus
- Risk Factors
- SARS-CoV-2
- Severity of Illness Index
9 Authors
- Guillaume Butler-Laporte
- Tomoko Nakanishi
- Vincent Mooser
- Alessandra Renieri
- Sara Amitrano
- Sirui Zhou
- Yiheng Chen
- Vincenzo Forgetta
- J Brent Richards
1 Application
| Application ID | Title |
|---|---|
| 27449 | Genetic Association to Phenotypic Variance and its Role in Human Health |
Enabling scientific discoveries that improve human health