SynthesisBlood2015
Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 5 pooled it
5.7field-weighted citation impact, top 4% 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 5 syntheses or guidelines pooled it, 80 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
- Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.Circulation · 2019Pooled it
- Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation.Platelets · 2019Pooled it
- Pooled it
- A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.Human molecular genetics · 2016Pooled it
- Trial
- Fibrinogen-associated plasma metabolites and implications for coagulation, inflammation, and vascular diseases.Journal of thrombosis and haemostasis : JTH · 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
- Epidemiology, fibrinogen, clot properties, and cardiovascular disease risk-an African perspective.Research and practice in thrombosis and haemostasis · 2025Article
- Implementation and clinical utility of multigene panels for bleeding, platelet, and thrombotic disorders.Journal of thrombosis and haemostasis : JTH · 2025Review
- Rare variants inERJ open research · 2025Article
- Thrombotic risk determined byResearch and practice in thrombosis and haemostasis · 2025Article
- Identification of multiple novel procoagulant plasma ligands for stabilin-2.Journal of thrombosis and haemostasis : JTH · 2025Article
- Acquired von Willebrand syndrome secondary to monoclonal gammopathy: a single-center case series.Therapeutic advances in hematology · 2025Article
- Article
- Regulation of fibrinogen synthesis.Thrombosis research · 2024Review
- Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024Review
- A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.Blood · 2024Article
- CD36 regulates factor VIII secretion from liver endothelial cells.Blood advances · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
67 authors at 20 institutions in 7 countries.
Jennifer E HuffmanMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; The Framingham Heart Study, Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, Framingham, MA; The Framingham Heart Study, Framingham, MA, and the Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;ORCID http://orcid.org/0000-0002-9672-2491
Paul S de VriesDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands;
Alanna C MorrisonHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX;
Maria Sabater-LlealCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden;ORCID http://orcid.org/0000-0002-0128-379X
Tim KacprowskiDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany;ORCID http://orcid.org/0000-0002-5393-2413
Paul L AuerJoseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI;
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA;
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA;
Ming-Huei ChenDepartment of Neurology, Boston University School of Medicine, Boston, MA;ORCID http://orcid.org/0000-0002-7036-3160
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and Department of Pediatrics, Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA;
Li-An LinHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX; Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX;
Riccardo E MarioniCentre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia;
Martina Müller-NurasyidInstitute of Genetic Epidemiology, Helmholtz Centre Munich-German Research Center for Environmental Health, Neuherberg, Germany; Department of Medicine I, Ludwig-Maximilians-University Munich, Munich, Germany; German Centre for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany;
Lisa R YanekGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD;
Nathan PankratzDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN;
Megan L GroveHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX;
Moniek P M de MaatDepartment of Hematology, Erasmus MC, Rotterdam, The Netherlands;ORCID http://orcid.org/0000-0001-7749-334X
Mary CushmanDepartments of Medicine and Pathology, University of Vermont, Colchester, VT;
Kerri L WigginsCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA;
Lihong QiUniversity of California at Davis, Davis, CA;
Bengt SennbladCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden; Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden;
Sarah E HarrisCentre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;
Ozren PolasekDepartment of Public Health, Faculty of Medicine, University of Split, Split, Croatia;
Helene RiessInstitute of Epidemiology II, Helmholtz Centre Munich-German Research Center for Environmental Health, Neuherberg, Germany; Department of Internal Medicine II-Cardiology, University of Ulm Medical School, Ulm, Germany;
Fernando RivadeneiraDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands;
Lynda M RoseDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA;
Anuj GoelRadcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and Department of Pediatrics, Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA;
Alexander TeumerStudy of Health in Pomerania/ Clinical and Epidemiological Research Department, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany;
André G UitterlindenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands;
Dhananjay VaidyaGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
Jie YaoThe Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and.
Weihong TangDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;
Daniel LevyThe Framingham Heart Study, Framingham, MA, and the Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
Melanie WaldenbergerGerman Centre for Cardiovascular Research, partner site Munich Heart Alliance, Munich, Germany; Institute of Epidemiology II, Helmholtz Centre Munich-German Research Center for Environmental Health, Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Centre Munich-German Research Center for Environmental Health, Neuherberg, Germany;ORCID http://orcid.org/0000-0003-0583-5093
Diane M BeckerGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;
Aaron R FolsomDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN;
Franco GiulianiniDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA;
Andreas GreinacherInstitute of Immunology and Transfusion Medicine, Department of Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany;
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands;
Chiang-Ching HuangJoseph J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI;
Charles KooperbergFred Hutchinson Cancer Research Center, Seattle, WA;ORCID http://orcid.org/0000-0002-7986-8560
Angela SilveiraCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden;
John M StarrCentre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Alzheimer Scotland Dementia Research Centre, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom;ORCID http://orcid.org/0000-0002-3059-7579
Konstantin StrauchInstitute of Genetic Epidemiology, Helmholtz Centre Munich-German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany;
Rona J StrawbridgeCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden;ORCID http://orcid.org/0000-0001-8506-3585
Alan F WrightMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;
Barbara McKnightDepartment of Biostatistics, University of Washington, Seattle, WA;
Oscar H FrancoDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands;
Neil ZakaiDepartments of Medicine and Pathology, University of Vermont, Colchester, VT;
Rasika A MathiasGeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD;
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA; Department of Epidemiology, and Department of Health Services, University of Washington, Seattle, WA; Group Health Research Institute, Group Health Cooperative, Seattle, WA;
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA;
Geoffrey H ToflerRoyal North Shore Hospital, University of Sydney, Sydney, NSW, Australia;
Uwe VölkerDepartment of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany;
Hugh WatkinsRadcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom;
Myriam FornageHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX; Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX;
Anders HamstenCardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden;
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom;
Eric BoerwinkleHuman Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX;
Wolfgang KoenigDepartment of Internal Medicine II-Cardiology, University of Ulm Medical School, Ulm, Germany; German Heart Centre Munich, Munich Technical University, Munich, Germany; and.
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, and Department of Pediatrics, Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA;
Caroline HaywardMedical Research Council Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom;ORCID http://orcid.org/0000-0002-9405-9550
Abbas DehghanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands;
Alex P ReinerFred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology, and.
Christopher J O'DonnellThe Framingham Heart Study, Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, Framingham, MA;
Nicholas L SmithDepartment of Epidemiology, and Group Health Research Institute, Group Health Cooperative, Seattle, WA; Seattle Epidemiologic Research and Information Center, Veterans Affairs Office of Research and Development, Seattle, WA.
Erasmus MC · NLBrigham and Women's Hospital · USJohns Hopkins University · USKarolinska Institutet · SEHelmholtz Zentrum München · DEInstitute of Genetics and Cancer · GBNational Heart Lung and Blood Institute · USUniversity of California, Los Angeles · USUniversity of Minnesota · USUniversity of Washington · USBrown Foundation · USFred Hutch Cancer Center · USGroup Health Cooperative · USJohn Radcliffe Hospital · GBThe University of Texas Health Science Center at Houston · USUniversität Greifswald · DEUniversitätsmedizin Greifswald · DEUniversität Ulm · DEUniversity of Vermont · USUniversity of Wisconsin–Milwaukee · US
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MEpidemiology 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
$8.9MGenomic Epidemiology of Cardiovascular DiseaseZIAHL006002 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2009 to 2015
$8.0MA Family-based Exome Sequencing Approach to Identify Platelet Aggregation GenesR01HL112064 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MATHIAS, RASIKA ANN · 2012 to 2015
$5.1MThe Women's Health Study: Infrastructure Support for Continued Cohort Follow-upUM1CA182913 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 2014 to 2018
$4.0MGene Expression for Functional Genomics in Human PopulationsZIAHL006175 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.2MFunctional Genetic Variation Underlying Cardiovascular Genomic EpidemiologyZIAHL006173 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.0MFHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600kBiotechnology and Biological Sciences Research Council BB/F019394/1Chief Scientist Office CZB/4/505Chief Scientist Office ETM/55Medical Research Council G0700704Medical Research Council MC_PC_U127561128Medical Research Council MR/K026992/1NCATS NIH HHS UL1 TR000124NCI NIH HHS P30 CA015704NCI NIH HHS UM1 CA182913NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL120393NIDDK NIH HHS P30 DK063491NIH HHS S10 OD020069
Abstract
Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76,000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified common variants. In addition, associations at KCNT1, HID1, and KATNB1 identified new candidate genes related to hemostasis for follow-up replication and functional genomic analysis. Newly identified low-frequency and rare-variant associations accounted for modest amounts of trait variance and therefore are unlikely to increase predicted trait heritability but provide new information for understanding individual variation in hemostasis pathways.
Indexed as
Cohort StudiesFactor VIIFactor VIIIFibrinogenGene FrequencyGenetic Association StudiesGenetic VariationHumansNerve Tissue ProteinsPolymorphism, Single NucleotidePotassium ChannelsPotassium Channels, Sodium-Activatedvon Willebrand FactorFactor VIIFactor VIIIFibrinogenKCNT1 protein, humanNerve Tissue ProteinsPotassium ChannelsPotassium Channels, Sodium-Activatedvon Willebrand Factor
Identifiers
What OpenQuestion holds
Textmetadata
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 OpenQuestion graph.