Evidence map›Paper›PMID 35387486›Full record

SynthesisCirculation2022

Genetic Landscape of the ACE2 Coronavirus Receptor.

Zhijian Yang, Erin Macdonald-Dunlop, Jiantao Chen, Ranran Zhai, Ting Li, Anne Richmond, Lucija Klarić, Nicola Pirastu, Zheng Ning, Chenqing Zheng and 61 more

Erratum issuedOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 3 pooled it
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 39 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

71 authors at 20 institutions in 13 countries.

Zhijian Yang *Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).ORCID 0000-0003-4803-8633
Erin Macdonald-Dunlop *Centre for Global Health Research, Usher Institute, University of Edinburgh, UK (E.M.-D., N.P., Y.H., P.K.J., J.F.W., X.S.).
Jiantao ChenBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).ORCID 0000-0002-7214-2257
Ranran ZhaiBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).ORCID 0000-0002-5834-9120
Ting LiBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).
Anne RichmondMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).
Lucija KlarićMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).ORCID 0000-0003-3105-8929
Nicola PirastuCentre for Global Health Research, Usher Institute, University of Edinburgh, UK (E.M.-D., N.P., Y.H., P.K.J., J.F.W., X.S.).ORCID 0000-0002-5363-3886
Zheng NingBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).ORCID 0000-0002-0451-6536
Chenqing ZhengBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).
Yipeng WangBiostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).
Tingting HuangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Z.N., T.H., Y.C., Y.P., A.M., X.S.).ORCID 0000-0003-2314-4448
Yazhou HeCentre for Global Health Research, Usher Institute, University of Edinburgh, UK (E.M.-D., N.P., Y.H., P.K.J., J.F.W., X.S.).ORCID 0000-0003-2358-0143
Huiming GuoDepartment of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences, Guangzhou, China (H.G.).
Kejun YingDivision of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.Y.).ORCID 0000-0002-1791-6176
Stefan GustafssonDepartment of Medical Sciences, Uppsala University, Sweden (A.S., S.G., L.W., L.L.).
Bram PrinsBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK (B.P., J.E.P., A.S.B.).
Anna RamischDepartment of Genetic Medicine and Development, University of Geneva Medical School, Switzerland (A. Ramisch, E.T.D., A.V.).ORCID 0000-0002-0641-4330
Emmanouil T DermitzakisDepartment of Genetic Medicine and Development, University of Geneva Medical School, Switzerland (A. Ramisch, E.T.D., A.V.).
Grace PngInstitute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany (G.P., A.G., E.Z.).ORCID 0000-0003-3962-7436
Niclas ErikssonUppsala Clinical Research Center, Sweden (N.E.).ORCID 0000-0002-2152-4343
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.H., C.K., A.P.R.).
Xiaowei HuCenter for Public Health Genomics, University of Virginia, Charlottesville (X.H., A.W.M.).
Daniela ZanettiDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (D.Z., T.L.A.).ORCID 0000-0002-1225-1021
Thibaud BoutinMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).
Shih-Jen HwangFramingham Heart Study, MA (S.-J.H., C.Y., D.L.).ORCID 0000-0002-2129-5704
Eleanor WheelerMRC Epidemiology Unit, University of Cambridge, UK (E.W., M.P., C.L.).
Maik PietznerMRC Epidemiology Unit, University of Cambridge, UK (E.W., M.P., C.L.).
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill (L.M.R.).ORCID 0000-0002-7892-193X
Anette KalnapenkisEstonian Genome Centre, Institute of Genomics, University of Tartu, Estonia (A.K., U.V., T.E.).
James E PetersDepartment of Immunology and Inflammation, Imperial College London, UK (J.E.P.).
Ana ViñuelaDepartment of Genetic Medicine and Development, University of Geneva Medical School, Switzerland (A. Ramisch, E.T.D., A.V.).ORCID 0000-0003-3771-8537
Arthur GillyInstitute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany (G.P., A.G., E.Z.).
Sölve ElmståhlFaculty of Medicine, Lund University, Sweden (S. Elmståhl).
George DedoussisDepartment of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Greece (G.D.).
John R PetrieInstitute of Cardiovascular & Medical Sciences, University of Glasgow, UK (J. Petrie).
Ozren PolašekUniversity of Split School of Medicine, Croatia (O.P.).
Lasse FolkersenDanish National Genome Center, Copenhagen, Denmark (L.F.).ORCID 0000-0003-0708-9530
Yan ChenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Z.N., T.H., Y.C., Y.P., A.M., X.S.).ORCID 0000-0001-9673-9712
Chen YaoFramingham Heart Study, MA (S.-J.H., C.Y., D.L.).
Urmo VõsaEstonian Genome Centre, Institute of Genomics, University of Tartu, Estonia (A.K., U.V., T.E.).
Erola Pairo-CastineiraMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).
Sara ClohiseyRoslin Institute, University of Edinburgh, Easter Bush, UK (E.P.-C., S.C., K.R., J.K.B.).
Andrew D BretherickMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).
Konrad RawlikRoslin Institute, University of Edinburgh, Easter Bush, UK (E.P.-C., S.C., K.R., J.K.B.).
GenOMICC Consortium†
IMI-DIRECT Consortium†
Tõnu EskoEstonian Genome Centre, Institute of Genomics, University of Tartu, Estonia (A.K., U.V., T.E.).
Stefan EnrothDepartment of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Sweden (S. Enroth, A.J., U.G.).
Åsa JohanssonDepartment of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Sweden (S. Enroth, A.J., U.G.).
Ulf GyllenstenDepartment of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Sweden (S. Enroth, A.J., U.G.).
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge, UK (E.W., M.P., C.L.).ORCID 0000-0002-5017-7344
Daniel LevyFramingham Heart Study, MA (S.-J.H., C.Y., D.L.).ORCID 0000-0003-1843-8724
Caroline HaywardMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, UK (A. Richmond, L.K., T.B., E.P.-C., A.D.B., C.H., J.F.W.).ORCID 0000-0002-9405-9550
Themistocles L AssimesDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, CA (D.Z., T.L.A.).ORCID 0000-0003-2349-0009
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.H., C.K., A.P.R.).ORCID 0000-0002-7986-8560
Ani W ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville (X.H., A.W.M.).
Agneta SiegbahnDepartment of Medical Sciences, Uppsala University, Sweden (A.S., S.G., L.W., L.L.).
Lars WallentinDepartment of Medical Sciences, Uppsala University, Sweden (A.S., S.G., L.W., L.L.).
Lars LindDepartment of Medical Sciences, Uppsala University, Sweden (A.S., S.G., L.W., L.L.).ORCID 0000-0003-2335-8542
Eleftheria ZegginiInstitute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany (G.P., A.G., E.Z.).
Jochen M SchwenkAffinity Proteomics, Science for Life Laboratory, KTH Royal Institute of Technology, Solna, Sweden (J.M.S.).ORCID 0000-0001-8141-8449
Adam S ButterworthBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, UK (B.P., J.E.P., A.S.B.).ORCID 0000-0002-6915-9015
Karl MichaëlssonDepartment of Surgical Sciences, Uppsala University, Sweden (K.M.).ORCID 0000-0003-2815-1217
Yudi PawitanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Z.N., T.H., Y.C., Y.P., A.M., X.S.).
Peter K JoshiCentre for Global Health Research, Usher Institute, University of Edinburgh, UK (E.M.-D., N.P., Y.H., P.K.J., J.F.W., X.S.).ORCID 0000-0002-6361-5059
J Kenneth BaillieRoslin Institute, University of Edinburgh, Easter Bush, UK (E.P.-C., S.C., K.R., J.K.B.).
Anders MälarstigDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Z.N., T.H., Y.C., Y.P., A.M., X.S.).
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (J.H., C.K., A.P.R.).ORCID 0000-0002-1427-4470
James F Wilson *Centre for Global Health Research, Usher Institute, University of Edinburgh, UK (E.M.-D., N.P., Y.H., P.K.J., J.F.W., X.S.).
Xia Shen *Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China (Z.Y., J.C., R.Z., T.L., Z.N., C.Z., Y.W., X.S.).ORCID 0000-0003-4390-1979
Sun Yat-sen University · CNEdinburgh Cancer Research · GBUppsala University · SERoslin Institute · GBBritish Heart Foundation · GBCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAEstonian Biocentre · EEKarolinska Institutet · SENational Heart Lung and Blood Institute · USScience for Life Laboratory · SEUniversity of Geneva · CHBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DECardiovascular Institute of the South · USCentre for Global Health Research · CAUniversity of Virginia · USWellcome Sanger Institute · GBAlgebra Bernays University · HRBrigham and Women's Hospital · USDanish National Centre for Social Research · DKGuangdong Academy of Medical Sciences · CN

Funding

Framingham Project/LevyZIAHL006001 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVY, DANIEL · 2009 to 2025
$51.1M
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7M
Proteomic determinants of direct measures of insulin sensitivityR01DK114183 · NIDDK · STANFORD UNIVERSITY · PI ASSIMES, THEMISTOCLES LEONARD · 2018 to 2022
$3.5M
Thrombosis genetics in African AmericansR01HL132947 · NHLBI · UNIVERSITY OF WASHINGTON · PI LANGE, LESLIE A, REINER, ALEXANDER P · 2017 to 2020
$3.1M
British Heart Foundation CH/12/2/29428British Heart Foundation RG/13/13/30194British Heart Foundation RG/18/13/33946Medical Research Council MC_UU_00006/1Medical Research Council MC_UU_00007/10Medical Research Council MC_UU_12015/1Medical Research Council MR/R026408/1NHLBI NIH HHS R01 HL132947NHLBI NIH HHS R01 HL146500NIDDK NIH HHS R01 DK114183Wellcome Trust 204979/Z/16/Z
6 · The paper itself

Abstract

backgroundSARS-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.

methodsWe 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.

resultsWe 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];

conclusionsHuman 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.

Indexed as

Angiotensin-Converting Enzyme 2COVID-19Cross-Sectional StudiesGenome-Wide Association StudyHumansReceptors, CoronavirusSARS-CoV-2ACE2 protein, humanAngiotensin-Converting Enzyme 2Receptors, Coronavirusangiotensin-converting enzyme 2cardiovascular diseasesCOVID-19Genome-Wide Association StudySARS-CoV-2

Identifiers

PMID35387486
PMCPMC9047645
OpenAlexW4225248532

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.