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Soc. open sci."],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>\n                    Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of\n                    <jats:italic>ACE2<\/jats:italic>\n                    and\n                    <jats:italic>TMPRSS2<\/jats:italic>\n                    in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung\n                    <jats:italic>ACE2<\/jats:italic>\n                    and\n                    <jats:italic>TMPRSS2<\/jats:italic>\n                    gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with\n                    <jats:italic>ACE2<\/jats:italic>\n                    gene expression in the Lung eQTL Consortium (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung\n                    <jats:italic>ACE2<\/jats:italic>\n                    gene expression in the Gene-Tissue Expression (GTEx) study (\n                    <jats:italic>p<\/jats:italic>\n                    = 4 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ) and with circulating plasma ACE2 levels in the INTERVAL study (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.03), but not with lung\n                    <jats:italic>ACE2<\/jats:italic>\n                    expression in the Lung eQTL Consortium study (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung\n                    <jats:italic>ACE2<\/jats:italic>\n                    and\n                    <jats:italic>TMPRSS2<\/jats:italic>\n                    expression or plasma ACE2 levels.\n                  <\/jats:p>","DOI":"10.1098\/rsos.200958","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T03:05:33Z","timestamp":1605668733000},"page":"200958","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["ACE inhibition and cardiometabolic risk factors, lung\n                    <i>ACE2<\/i>\n                    and\n                    <i>TMPRSS2<\/i>\n                    gene expression, and plasma ACE2 levels: a Mendelian randomization study"],"prefix":"10.1098","volume":"7","author":[{"given":"Dipender","family":"Gill","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, St Mary's Hospital, Imperial College London, Medical School Building, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marios","family":"Arvanitis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana I.","family":"Hern\u00e1ndez Cordero","sequence":"additional","affiliation":[{"name":"The University of British Columbia Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, 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