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Genetic Landscape o...
Genetic Landscape of the ACE2 Coronavirus Receptor
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- Yang, Zhijian (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, 2nd Nanjiang Rd, Guangzhou 511458, Peoples R China.,Fudan University,Sun Yat-sen University
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- Macdonald-Dunlop, Erin (författare)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
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- Chen, Jiantao (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, 2nd Nanjiang Rd, Guangzhou 511458, Peoples R China.
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visa fler...
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- Zhai, Ranran (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, 2nd Nanjiang Rd, Guangzhou 511458, Peoples R China.
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- Li, Ting (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, 2nd Nanjiang Rd, Guangzhou 511458, Peoples R China.
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- Richmond, Anne (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Klaric, Lucija (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Pirastu, Nicola (författare)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Human Technopole Viale Rita Levi Montalcini, Milan, Italy.
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- Ning, Zheng (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
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- Zheng, Chenqing (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.
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- Wang, Yipeng (författare)
- Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China.
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- Huang, Tingting (författare)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
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- He, Yazhou (författare)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Sichuan Univ, West China Fourth Hosp, West China Sch Publ Hlth, Chengdu, Peoples R China.
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- Guo, Huiming (författare)
- Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Dept Cardiac Surg, Guangzhou, Peoples R China.
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- Ying, Kejun (författare)
- Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
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- Gustafsson, Stefan (författare)
- Uppsala universitet,Klinisk epidemiologi
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- Prins, Bram (författare)
- Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.
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- Ramisch, Anna (författare)
- Univ Geneva, Sch Med, Dept Genet Med & Dev, Geneva, Switzerland.
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- Dermitzakis, Emmanouil T. (författare)
- Univ Geneva, Sch Med, Dept Genet Med & Dev, Geneva, Switzerland.
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- Png, Grace (författare)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Translat Genom, Neuherberg, Germany.;Tech Univ Munich TUM, Sch Med, Munich, Germany.
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- Eriksson, Niclas, 1978- (författare)
- Uppsala universitet,Uppsala kliniska forskningscentrum (UCR)
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- Haessler, Jeffrey (författare)
- Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
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- Hu, Xiaowei (författare)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
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- Zanetti, Daniela (författare)
- Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
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- Boutin, Thibaud (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Hwang, Shih-Jen (författare)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Wheeler, Eleanor (författare)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.
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- Pietzner, Maik (författare)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Charite, Berlin Inst Hlth, Computat Med, Berlin, Germany.
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- Raffield, Laura M. (författare)
- Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
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- Kalnapenkis, Anette (författare)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia.
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- Peters, James E. (författare)
- Imperial Coll London, Dept Immunol & Inflammat, London, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.
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- Vinuela, Ana (författare)
- Univ Geneva, Sch Med, Dept Genet Med & Dev, Geneva, Switzerland.;Newcastle Univ, Fac Med Sci, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England.
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- Gilly, Arthur (författare)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Translat Genom, Neuherberg, Germany.;Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England.
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- Elmståhl, S. (författare)
- Lund University,Lunds universitet,Geriatrik,Forskargrupper vid Lunds universitet,Geriatrics,Lund University Research Groups
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- Dedoussis, George (författare)
- Harokopio Univ Athens, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece.
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- Petrie, John R. (författare)
- Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
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- Polasek, Ozren (författare)
- Univ Split, Sch Med, Split, Croatia.;Algebra Univ Coll, Zagreb, Croatia.
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- Folkersen, Lasse (författare)
- Danish Natl Genome Ctr, Copenhagen, Denmark.
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- Chen, Yan (författare)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.,Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Yao, Chen (författare)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Vosa, Urmo (författare)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
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- Pairo-Castineira, Erola (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
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- Clohisey, Sara (författare)
- Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
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- Bretherick, Andrew D. (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Rawlik, Konrad (författare)
- Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.
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- Esko, Tonu (författare)
- Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
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- Enroth, Stefan, 1976- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Johansson, Åsa (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Gyllensten, Ulf B. (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Medicinsk genetik och genomik
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- Langenberg, Claudia (författare)
- Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.;Charite, Berlin Inst Hlth, Computat Med, Berlin, Germany.
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- Levy, Daniel (författare)
- Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
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- Hayward, Caroline (författare)
- Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Lind, Lars (författare)
- Uppsala universitet,Klinisk epidemiologi
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- Kooperberg, Charles (författare)
- Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
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- Manichaikul, Ani W. (författare)
- Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
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- Siegbahn, Agneta, 1947- (författare)
- Uppsala universitet,Koagulation och inflammationsvetenskap
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- Wallentin, Lars, 1943- (författare)
- Uppsala universitet,Kardiologi
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- Lind, Lars (författare)
- Uppsala universitet,Klinisk epidemiologi
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- Zeggini, Eleftheria (författare)
- German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Translat Genom, Neuherberg, Germany.;Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England.;Tech Univ Munich TUM, Munich, Germany.;Klinikum Rechts Der Isar, TUM Sch Med, Munich, Germany.
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- Schwenk, Jochen M. (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Affin Prote, Sci Life Lab, Solna, Sweden.,KTH Royal Inst Technol, Affin Prote, Sci Life Lab, Solna, Sweden.
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- Butterworth, Adam S. (författare)
- Univ Cambridge, Dept Publ Hlth & Primary Care, British Heart Fdn, Cardiovasc Epidemiol Unit, Cambridge, England.;Wellcome Genome Campus, Hlth Data Res UK Cambridge, Cambridge, England.;Univ Cambridge, Cambridge, England.;Univ Cambridge, British Heart Fdn, Ctr Res Excellence, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res, Blood & Transplant Res Unit Donor Hlth & Genom, Cambridge, England.
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- Michaëlsson, Karl, 1959- (författare)
- Uppsala universitet,Medicinsk epidemiologi
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- Pawitan, Yudi (författare)
- Karolinska Institutet
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- Joshi, Peter K. (författare)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
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- Baillie, J. Kenneth (författare)
- Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian, Scotland.;Royal Infirm Edinburgh NHS Trust, Intens Care Unit, Edinburgh, Midlothian, Scotland.
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- Malarstig, Anders (författare)
- Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Pfizer Worldwide Res Dev & Med, Stockholm, Sweden.
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- Reiner, Alexander P. (författare)
- Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
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- Wilson, James F. (författare)
- Univ Edinburgh, Usher Inst, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Canc, Western Gen Hosp, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
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- Shen, Xia (författare)
- Karolinska Institutet,Fudan University,Sun Yat-sen University,University of Edinburgh
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Sun Yat Sen Univ, Sch Life Sci, Biostat Grp, Guangzhou, Peoples R China;Fudan Univ, Greater Bay Area Inst Precis Med Guangzhou, Ctr Intelligent Med Res, 2nd Nanjiang Rd, Guangzhou 511458, Peoples R China. Fudan University (creator_code:org_t)
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et al
- Ovid Technologies (Wolters Kluwer Health), 2022
- 2022
- Engelska.
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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https://lup.lub.lu.s...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Nyckelord
- angiotensin-converting enzyme 2
- Genome-Wide Association Study
- cardiovascular diseases
- COVID-19
- SARS-CoV-2
- angiotensin-converting enzyme 2
- cardiovascular diseases
- COVID-19
- Genome-Wide Association Study
- SARS-CoV-2
- angiotensin converting enzyme 2
- dipeptidyl carboxypeptidase
- Article
- cardiometabolic risk
- cardiovascular disease
- chromosome analysis
- computer model
- coronavirus disease 2019
- data extraction
- disorder of sex development
- gene amplification
- gene expression
- gene frequency
- genetic analysis
- genetic correlation
- genetic profile
- genetic variability
- genome-wide association study
- genotype
- heritability
- human
- human cell
- information processing
- information retrieval
- omics
- outcome assessment
- protein expression
- quantitative trait locus
- real time polymerase chain reaction
- Severe acute respiratory syndrome coronavirus 2
- single nucleotide polymorphism
- cross-sectional study
- genetics
- meta analysis
- metabolism
- Angiotensin-Converting Enzyme 2
- Cross-Sectional Studies
- Humans
- Peptidyl-Dipeptidase A
- Receptors, Coronavirus
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Yang, Zhijian
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Macdonald-Dunlop ...
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Chen, Jiantao
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Zhai, Ranran
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Li, Ting
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Richmond, Anne
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Klaric, Lucija
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Pirastu, Nicola
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Ning, Zheng
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Zheng, Chenqing
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Wang, Yipeng
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Huang, Tingting
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He, Yazhou
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Guo, Huiming
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Ying, Kejun
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Gustafsson, Stef ...
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Prins, Bram
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Ramisch, Anna
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Dermitzakis, Emm ...
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Png, Grace
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Eriksson, Niclas ...
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Haessler, Jeffre ...
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Hu, Xiaowei
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Zanetti, Daniela
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Boutin, Thibaud
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Hwang, Shih-Jen
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Wheeler, Eleanor
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Pietzner, Maik
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Raffield, Laura ...
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Kalnapenkis, Ane ...
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Peters, James E.
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Vinuela, Ana
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Gilly, Arthur
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Elmståhl, S.
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Dedoussis, Georg ...
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Petrie, John R.
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Polasek, Ozren
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Folkersen, Lasse
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Chen, Yan
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Yao, Chen
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Vosa, Urmo
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Pairo-Castineira ...
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Clohisey, Sara
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Bretherick, Andr ...
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Rawlik, Konrad
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Esko, Tonu
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Enroth, Stefan, ...
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Johansson, Åsa
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Gyllensten, Ulf ...
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Langenberg, Clau ...
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Levy, Daniel
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Hayward, Carolin ...
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Lind, Lars
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Kooperberg, Char ...
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Manichaikul, Ani ...
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Siegbahn, Agneta ...
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Wallentin, Lars, ...
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Zeggini, Elefthe ...
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Schwenk, Jochen ...
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Butterworth, Ada ...
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Michaëlsson, Kar ...
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Pawitan, Yudi
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Joshi, Peter K.
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Baillie, J. Kenn ...
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Malarstig, Ander ...
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Reiner, Alexande ...
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Wilson, James F.
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Shen, Xia
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