SynthesisCirculation2019
Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.
Registry-linked trialOpen access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05116501 (Novel Insights Into the Genetic Background of Patients With Low Von Willebrand Factor Levels Using Next-generation Sequencing), which is not on this map. Cited by 99 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 2 pooled it
13.4field-weighted citation impact, top 1% of its field
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.
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.
Novel Insights Into the Genetic Background of Patients With Low Von Willebrand Factor Levels Using Next-generation Sequencing
Who cites it
99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 167 citations in OpenAlex.
- The contribution of the sinusoidal endothelial cell receptors CLEC4M, stabilin-2, and SCARA5 to VWF-FVIII clearance in thrombosis and hemostasis.Journal of thrombosis and haemostasis : JTH · 2023Pooled it
- The effects of coagulation factors on the risk of endometriosis: a Mendelian randomization study.BMC medicine · 2023Pooled it
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- Leveraging Mendelian randomization to inform drug discovery and development for ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Von Willebrand disease: A century of progress.Research and practice in thrombosis and haemostasis · 2026Review
- Multi-trait and Gene-Based Analyses Identify Genetic Variants Associated with Spontaneous Coronary Artery Dissection.medRxiv : the preprint server for health sciences · 2026Article
- RAB5C Increases Endothelial Release of VWF by Regulating Vesicle Trafficking.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Review
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- DAB2IP: unifying cardiovascular pathogenesis and cardiovascular brain crosstalk.Frontiers in cardiovascular medicine · 2026Review
- Molecular genetic testing in von Willebrand disease: past, present, and beyond.Haematologica · 2026Review
- Association Between Hemostatic Profiles and Hypertensive Disorders of Pregnancy: A Multi-Omics Mendelian Randomization Study.International journal of women's health · 2026Article
- A Novel Complete F8 Tandem Duplication Causing Elevated Factor VIII Activity and Associated with Venous Thromboembolism.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Diagnosis of von Willebrand disease.Blood advances · 2025Review
- Von Willebrand factor and JAK2V617F variant allele frequency predict thrombosis and bleeding in patients with myeloproliferative neoplasms.Annals of hematology · 2025Article
- Efficient candidate drug target discovery through proteogenomics in a Scottish cohort.Communications biology · 2025Article
- Proteomics on choroidal neovascularization based on itraq and the protective effect of TAB1 in CNV.Scientific reports · 2025Article
- Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
77 authors at 3 institutions in 3 countries.
Maria Sabater-LlealCardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden (M.S.-L.).
Jennifer E HuffmanPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health (P.S.d.V., E.B., M.F., A.C.M.), University of Texas Health Science Center at Houston.
Jonathan MartenMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (J.M., J.F.W., C.H.), University of Edinburgh, Scotland.
Michael A MastrangeloAab Cardiovascular Research Institute, University of Rochester Medical Center, NY (M.A.M., C.J.L.).
Ci SongPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis (N.P.).
Cavin K Ward-CavinessEnvironmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, NC (C.K.W.-C.).
Lisa R YanekGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., D.V., D.M.B., L.C.B.).
Stella TrompetDepartment of Geriatrics and Gerontology (S.T.), Leiden University Medical Center, the Netherlands.
Graciela E DelgadoDepartment of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (G.E.D., M.E.K., W.M.).
Xiuqing GuoInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (X.G., J.I.R.).
Traci M BartzDepartment of Biostatistics (T.M.B., B.M.), University of Washington, Seattle.
Angel Martinez-PerezUnit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau, IIB-Sant Pau, Barcelona, Spain (M.S.-L., A.M.-P., J.M.S.).
Marine GermainInstitut national de la santé et de la recherche médicale (INSERM), UMR_S 1166, Team Genomics and Pathophysiology of Cardiovascular Diseases, Sorbonne Universités, Université Pierre-et-Marie-Curie, Paris, France (M.G., D.-A.T.).
Hugoline G de HaanDepartment of Clinical Epidemiology (H.G.d.H., A.v.H.V., F.R.R.), Leiden University Medical Center, the Netherlands.
Ayse B OzelDepartment of Human Genetics (A.B.O., J.Z.L., D.G.), University of Michigan, Ann Arbor.
Ozren PolasekFaculty of Medicine, University of Split, Croatia (O.P., I.K.).
Albert V SmithSchool of Public Health, Department of Biostatistics (A.V.S.), University of Michigan, Ann Arbor.
John D EicherFramingham Heart Study, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
Alex P ReinerDepartment of Epidemiology, (A.P.R., B.M.P., N.L.S.), University of Washington, Seattle.
Weihong TangDivision of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis (W.T.).
Neil M DaviesMedical Research Council Integrative Epidemiology Unit and Bristol Medical School (N.M.D.), University of Bristol, UK.
David J StottAcademic Section of Geriatrics, Faculty of Medicine (J.D.S.), University of Glasgow, UK.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Department of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (X.G., J.I.R.).
Geoffrey H ToflerRoyal North Shore Hospital, University of Sydney, Australia (G.H.T.).
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health (P.S.d.V., E.B., M.F., A.C.M.), University of Texas Health Science Center at Houston.
Moniek P M de MaatDepartment of Hematology (M.P.M.d.M.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Marcus E KleberDepartment of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (G.E.D., M.E.K., W.M.).
Paul WelshInstitute of Cardiovascular and Medical Sciences (P.W.), University of Glasgow, UK.
Jennifer A BrodyDepartment of Medicine (J.A.B., B.M.P.), University of Washington, Seattle.
Ming-Huei ChenPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
Dhananjay VaidyaGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., D.V., D.M.B., L.C.B.).
José Manuel SoriaUnit of Genomics of Complex Diseases, Institut d'Investigació Biomèdica Sant Pau, IIB-Sant Pau, Barcelona, Spain (M.S.-L., A.M.-P., J.M.S.).
Pierre SuchonLaboratory of Haematology, La Timone Hospital, Marseille, France (P.S., P.-E.M.).
Astrid van Hylckama VliegDepartment of Clinical Epidemiology (H.G.d.H., A.v.H.V., F.R.R.), Leiden University Medical Center, the Netherlands.
Karl C DeschDepartment of Pediatrics and Communicable Disease (K.D.C.), University of Michigan, Ann Arbor.
Ivana KolcicFaculty of Medicine, University of Split, Croatia (O.P., I.K.).
Peter K JoshiCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (P.K.J., H.C., I.R., J.F.W.), University of Edinburgh, Scotland.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences National Institute on Aging, Bethesda, MD (L.J.L., T.B.H.).
Tamara B HarrisLaboratory of Epidemiology and Population Sciences National Institute on Aging, Bethesda, MD (L.J.L., T.B.H.).
Harry CampbellCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (P.K.J., H.C., I.R., J.F.W.), University of Edinburgh, Scotland.
Igor RudanCentre for Global Health Research, Usher Institute for Population Health Sciences and Informatics (P.K.J., H.C., I.R., J.F.W.), University of Edinburgh, Scotland.
Diane M BeckerGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., D.V., D.M.B., L.C.B.).
Jun Z LiDepartment of Human Genetics (A.B.O., J.Z.L., D.G.), University of Michigan, Ann Arbor.
Fernando RivadeneiraDepartment of Internal Medicine (F.R., A.G.U.), Erasmus University Medical Center, Rotterdam, the Netherlands.
André G UitterlindenDepartment of Internal Medicine (F.R., A.G.U.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Albert HofmanDepartment of Epidemiology (P.S.d.V., A.H., O.H.F., A.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Oscar H FrancoDepartment of Epidemiology (P.S.d.V., A.H., O.H.F., A.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Mary CushmanLarner College of Medicine, University of Vermont, Colchester (M.C.).
Bruce M PsatyDepartment of Epidemiology, (A.P.R., B.M.P., N.L.S.), University of Washington, Seattle.
Pierre-Emmanuel MorangeLaboratory of Haematology, La Timone Hospital, Marseille, France (P.S., P.-E.M.).
Barbara McKnightDepartment of Biostatistics (T.M.B., B.M.), University of Washington, Seattle.
Michael R ChongMcMaster University, Population Health Research Institute, Population Health Research Institute, Biochemistry and Biomedical Sciences, Hamilton, Canada (M.R.C.).
Israel Fernandez-CadenasStroke Pharmacogenomics and genetics, Department of Neurology, Institut d'Investigació Biomedica Sant Pau, IIB-Sant Pau, Barcelona, Spain (I.F.-C.).
Jonathan RosandMassachusetts General Hospital, Broad Institute, Harvard Medical School, Boston (J.R.).
Arne LindgrenDepartment of Clinical Sciences Lund, Neurology, Lund University, Sweden (A.L.).
INVENT Consortium; MEGASTROKE Consortium of the International Stroke Genetics Consortium (ISGC)
Vilmundur GudnasonIcelandic Heart Association, Kopavogur (V.G.).
James F WilsonMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (J.M., J.F.W., C.H.), University of Edinburgh, Scotland.
Caroline HaywardMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (J.M., J.F.W., C.H.), University of Edinburgh, Scotland.
David GinsburgDepartment of Human Genetics (A.B.O., J.Z.L., D.G.), University of Michigan, Ann Arbor.
Myriam FornageHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health (P.S.d.V., E.B., M.F., A.C.M.), University of Texas Health Science Center at Houston.
Frits R RosendaalDepartment of Clinical Epidemiology (H.G.d.H., A.v.H.V., F.R.R.), Leiden University Medical Center, the Netherlands.
Juan Carlos SoutoUnit of Hemostasis and Thrombosis, Hospital de la Sant Creu i Sant Pau, Barcelona, Spain (J.C.S.).
Lewis C BeckerGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (L.R.Y., D.V., D.M.B., L.C.B.).
Nancy S JennyDepartment of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Colchester (N.S.J.).
Winfried MärzDepartment of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (G.E.D., M.E.K., W.M.).
J Wouter JukemaDepartment of Cardiology (S.T., J.W.J.), Leiden University Medical Center, the Netherlands.
Abbas DehghanDepartment of Epidemiology (P.S.d.V., A.H., O.H.F., A.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.
David-Alexandre TrégouëtInstitut national de la santé et de la recherche médicale (INSERM), UMR_S 1166, Team Genomics and Pathophysiology of Cardiovascular Diseases, Sorbonne Universités, Université Pierre-et-Marie-Curie, Paris, France (M.G., D.-A.T.).
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health (P.S.d.V., E.B., M.F., A.C.M.), University of Texas Health Science Center at Houston.
Andrew D JohnsonPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
Christopher J O'DonnellPopulation Sciences Branch, National Heart, Lung, and Blood Institute, Framingham, MA (J.E.H., C.S., J.D.E., M.-H.C., A.D.J., C.J.O.).
David P StrachanPopulation Health Research Institute, St George's, University of London, UK (D.P.S.).
Charles J LowensteinAab Cardiovascular Research Institute, University of Rochester Medical Center, NY (M.A.M., C.J.L.).
Nicholas L SmithDepartment of Epidemiology, (A.P.R., B.M.P., N.L.S.), University of Washington, Seattle.
Fondation pour l’innovation en Cadiométabolisme et Nutrition · FRLund University · SEUniversity of Iceland · IS
Funding
UC Davis Alzheimer's Disease Core CenterP30AG010129 · NIA · UNIVERSITY OF CALIFORNIA DAVIS · PI DECARLI, CHARLES · 1991 to 2020
$28.3MCardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3MPRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9MTemporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham CohortsR01AG054076 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DECARLI, CHARLES, SESHADRI, SUDHA · 2016 to 2020
$12.3MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MCHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6MCLINICAL PROJECT: Age, Gene/Environment Susceptibility Study on the Multi-omics of Aging: A clinical epidemiologic prospective studyZIAAG007380 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$6.1MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MThe Molecular Genetics of HemostasisR35HL135793 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GINSBURG, DAVID · 2017 to 2023
$4.1MMicroglial, Inflammatory and Omics Markers of Cerebral Small Vessel Disease in the CHARGE ConsortiumUH3NS100605 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI FORNAGE, MYRIAM, SESHADRI, SUDHA · 2018 to 2020
$3.0MIntramural NIH HHS Z01 AG007380Intramural NIH HHS Z99 AG999999Medical Research Council MC_UU_00007/10NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL134894NHLBI NIH HHS R35 HL135793NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114NIA NIH HHS P30 AG010129NIA NIH HHS R01 AG054076NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG052409NINDS NIH HHS R01 NS017950NINDS NIH HHS UH3 NS100605
Abstract
backgroundFactor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF.
methodsWe meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events.
resultsWe identified 13 novel genome-wide significant ( P≤2.5×10
conclusionsThe meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.
Indexed as
Genetic LociArterial Occlusive DiseasesBiomarkersBlood CoagulationBlood Coagulation Disorders, InheritedFactor VIIIGenetic MarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPhenotypeRibosomal Protein L3Risk FactorsVenous Thrombosisvon Willebrand FactorBiomarkersF8 protein, humanFactor VIIIGenetic MarkersRibosomal Protein L3RPL3 protein, humanvon Willebrand Factorcardiovascular diseasesfactor VIIIgeneticsgenome-wide association studiesrisk factorsvon Willebrand factor
Identifiers
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Registered trials
NCT05116501ClinicalTrials.gov
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 OpenQuestion graph.