ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels: a Mendelian randomization study

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Fältnamn	Indikatorer	Metadata
000		10945naa a2200805 4500
001		oai:DiVA.org:uu-429060
003		SwePub
008		201222s2020 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:145281848
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4290602 URI
024	7	a https://doi.org/10.1098/rsos.2009582 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1452818482 URI
040		a (SwePub)uud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Gill, Dipenderu Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.4 aut
245	1 0	a ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels :b a Mendelian randomization study
264		c 2020-11-18
264	1	b ROYAL SOC,c 2020
338		a electronic2 rdacarrier
520		a 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 ACE2 and TMPRSS2 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 ACE2 and TMPRSS2 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 ACE2 gene expression in the Lung eQTL Consortium (p = 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 ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 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 ACE2 and TMPRSS2 expression or plasma ACE2 levels.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653		a COVID-19
653		a Mendelian randomization
653		a angiotensin-converting enzyme inhibitors
653		a genetic epidemiology
700	1	a Arvanitis, Mariosu Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD USA.4 aut
700	1	a Carter, Paulu Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.4 aut
700	1	a Cordero, Ana I. Hernandezu Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.4 aut
700	1	a Jo, Brianu Lewis Sigler Inst Integrat Biol, Program Quantitat & Computat Biol, Princeton, NJ USA.4 aut
700	1	a Karhunen, Villeu Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.4 aut
700	1	a Larsson, Susanna C.u Karolinska Institutet,Uppsala universitet,Ortopedi,Karolinska Inst, Unit Cardiovasc & Nutr Epidemiol, Inst Environm Med, Stockholm, Sweden4 aut0 (Swepub:uu)susla720
700	1	a Li, Xuanu Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.4 aut
700	1	a Lockhart, Sam M.u Univ Cambridge, Med Res Council, Wellcome Trust Med Res Council Inst Metab Sci, Metab Dis Unit, Cambridge, England.4 aut
700	1	a Mason, Amyu Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.4 aut
700	1	a Pashos, Evanthiau Pfizer Worldwide Res Dev & Med, Internal Med Res Unit, Cambridge, MA USA.4 aut
700	1	a Saha, Ashisu Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD USA.4 aut
700	1	a Tan, Vanessa Y.u Univ Bristol, Med Res Council Integrat Epidemiol Unit, Bristol, Avon, England.;Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.4 aut
700	1	a Zuber, Verenau Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.;Univ Cambridge, Cambridge Inst Publ Hlth, Med Res Council, Biostat Unit, Cambridge, England.4 aut
700	1	a Bosse, Yohanu Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Laval, PQ, Canada.4 aut
700	1	a Fahle, Sarahu Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.4 aut
700	1	a Hao, Keu Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Icahn Inst Data Sci & Genom Technol, New York, NY 10029 USA.4 aut
700	1	a Jiang, Taou Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.4 aut
700	1	a Joubert, Philippeu Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Laval, PQ, Canada.4 aut
700	1	a Lunt, Alan C.u Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.;Cambridge Inst Publ Hlth, MRC Biostat Unit, Robinson Way, Cambridge CB2 0SR, England.4 aut
700	1	a Ouwehand, Willem Hendriku Univ Cambridge, Dept Haematol, Cambridge Biomed Campus, Cambridge, England. NHS Blood & Transplant, Biomed Campus, Cambridge, England. Wellcome Sanger Inst, Cambridge, England.4 aut
700	1	a Roberts, David J.u Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;NHS Blood & Transplant Oxford Ctr, John Radcliffe Hosp, Level 2, Oxford, England.;Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Oxford, England.4 aut
700	1	a Timens, Wimu Univ Groningen, Dept Pathol & Med Biol, Groningen, Netherlands.4 aut
700	1	a van den Berge, Maartenu Univ Groningen, Groningen Res Inst Asthma, Groningen, Netherlands.;Univ Groningen, COPD, Groningen, Netherlands.;Univ Groningen, Dept Pulmonol, Groningen, Netherlands.;Univ Groningen, Groningen Res Inst Asthma, Groningen, Netherlands.;Univ Groningen, COPD, Groningen, Netherlands.4 aut
700	1	a Watkins, Nicholas A.u Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.4 aut
700	1	a Battle, Alexisu Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.;Johns Hopkins Univ, Ctr Computat Biol, Baltimore, MD USA.4 aut
700	1	a Butterworth, Adam S.u Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.4 aut
700	1	a Danesh, Johnu Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.4 aut
700	1	a Di Angelantonio, Emanueleu Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.4 aut
700	1	a Engelhardt, Barbara E.u Princeton Univ, Comp Sci Dept, Princeton, NJ 08544 USA.;Princeton Univ, Ctr Stat & Machine Learning, Princeton, NJ 08544 USA.4 aut
700	1	a Peters, James E.u Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.;Imperial Coll London, Dept Immunol & Inflammat, Fac Med, London, England.4 aut
700	1	a Sin, Don D.u Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.4 aut
700	1	a Burgess, Stephenu Univ Cambridge, Med Res Council, Wellcome Trust Med Res Council Inst Metab Sci, Metab Dis Unit, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, Cambridge Inst Publ Hlth, Med Res Council, Biostat Unit, Cambridge, England.;Univ Cambridge, British Heart Fdn Ctr Res Excellence, Cambridge, England.;Univ Cambridge, Homerton Coll, Cambridge, England.;Uppsala Univ, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Cambridge, England.;Cambridge Univ Hosp, Cambridge, England.4 aut
710	2	a Imperial Coll London, St Marys Hosp, Dept Epidemiol & Biostatist, Med Sch Bldg, London, England.b Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD USA.4 org
773	0	t Royal Society Open Scienced : ROYAL SOCg 7:11q 7:11x 2054-5703
856	4	u https://uu.diva-portal.org/smash/get/diva2:1512329/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.200958
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-429060
856	4 8	u https://doi.org/10.1098/rsos.200958
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:145281848

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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