{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:32:19Z","timestamp":1775176339652,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lady Davis Institute of the Jewish General Hospital"},{"name":"Canadian Foundation for Innovation"},{"name":"NIH Foundation, Cancer Research UK"},{"name":"Research Fellowships of Japan Society for the Promotion of Science"},{"name":"JSPS Overseas Challenge Program for Young Researchers"},{"name":"FRQS Clinical Research Scholarship"},{"name":"Wellcome Trust, Medical Research Council, European Union"},{"name":"National Institute for Health Research (NIHR)-funded BioResource"},{"name":"Clinical Research Facility and Biomedical Research Centre based at Guy\u2019s and St Thomas\u2019 NHS Foundation Trust"},{"name":"UK Biobank","award":["27449"],"award-info":[{"award-number":["27449"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u00a0186 individuals of European ancestry were used for COVID-19 susceptibility, hospitalization and severe-disease outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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,\u00a01.15], hospitalization (OR: 0.86, 95% CI: 0.68, 1.08) or severe disease (OR: 0.74, 95% CI: 0.51,\u00a01.06). Using genetic variants from the AGES cohort, the result was similar for susceptibility (OR: 0.98, 95% CI: 0.89,\u00a01.09), hospitalization (OR: 0.86, 95% CI: 0.66, 1.11) and severity (OR: 0.75, 95% CI: 0.50,\u00a01.14). Multiple-sensitivity analyses led to similar results.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ije\/dyaa229","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T19:12:03Z","timestamp":1602875523000},"page":"75-86","source":"Crossref","is-referenced-by-count":13,"title":["The effect of angiotensin-converting enzyme levels on COVID-19 susceptibility and severity: a Mendelian randomization study"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-0396","authenticated-orcid":false,"given":"Guillaume","family":"Butler-Laporte","sequence":"first","affiliation":[{"name":"Centre for Clinical Epidemiology Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, QC, Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, 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