ArticleJournal of thrombosis and haemostasis : JTH2021
FGL1 as a modulator of plasma D-dimer levels: Exome-wide marker analysis of plasma tPA, PAI-1, and D-dimer.
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Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Historical review: more than two decades understanding the genetic architecture of hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2026Review
- Candidate biomarkers to identify mesothelioma patients at risk of developing venous thromboembolism post-surgery.Scientific reports · 2026Article
- Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus.Journal of translational autoimmunity · 2024Review
- FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle.Frontiers in pharmacology · 2024Article
- Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism.Journal of thrombosis and haemostasis : JTH · 2022Article
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Authors and funding
50 authors at 20 institutions in 7 countries.
Florian ThibordThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.ORCID 0000-0003-2229-8322
Ci SongThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.
Jack PatteeDivision of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
Benjamin A T RodriguezThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.
Ming-Huei ChenThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.
Christopher J O'DonnellThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.
Marcus E KleberVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Graciela E DelgadoVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Xiuqing GuoDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Jie YaoDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Kent D TaylorDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Ayse Bilge OzelDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, USA.
Barbara McKnightDepartment of Biostatistics, University of Washington, Seattle, Washington, USA.
Beata GyorgyINSERM UMRS1166, ICAN - Institute of CardioMetabolism and Nutrition, Sorbonne Université, Paris, France.
Eleanor SimonsickNational Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Hampton L LeonardNational Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Germán D CarrasquillaFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Marta Guindo-MartinezFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Angela SilveiraCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine and Karolinska University Hospital Solna, Stockholm, Sweden.
Gerard Temprano-SagreraGenomics of Complex Diseases, Research Institute of Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
Lisa R YanekGeneSTAR Research Program, Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Diane M BeckerGeneSTAR Research Program, Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Rasika A MathiasGeneSTAR Research Program, Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Lewis C BeckerGeneSTAR Research Program, Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Tuomas O KilpeläinenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Niels GrarupFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Oluf PedersenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Torben HansenFaculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Allan LinnebergCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
Anders HamstenCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine and Karolinska University Hospital Solna, Stockholm, Sweden.
Hugh WatkinsRadcliffe Department of Medicine, University of Oxford, Oxford, UK.
Maria Sabater-LlealCardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine and Karolinska University Hospital Solna, Stockholm, Sweden.
Mike A NallsNational Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
David-Alexandre TrégouëtINSERM UMRS1166, ICAN - Institute of CardioMetabolism and Nutrition, Sorbonne Université, Paris, France.
Pierre-Emmanuel MorangeINSERM, INRAE, Aix-Marseille Univ, Marseille, France.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, USA.
Russel P TracyDepartment of Pathology and Laboratory Medicine & Department of Medicine, Vermont Center on Cardiovascular and Brain Health, Larner College of Medicine at the University of Vermont, Burlington, Vermont, USA.
Nicholas L SmithCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, USA.ORCID 0000-0003-3483-353X
Karl C DeschDepartment of Pediatrics, Cell and Molecular Biology Program, University of Michigan, Ann Arbor, Michigan, USA.
Mary CushmanDepartment of Pathology and Laboratory Medicine & Department of Medicine, Vermont Center on Cardiovascular and Brain Health, Larner College of Medicine at the University of Vermont, Burlington, Vermont, USA.ORCID 0000-0002-7871-6143
Jerome I RotterDepartment of Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Nathan D PankratzDepartment of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Aaron R FolsomDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0003-2635-2699
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Winfried MärzVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Weihong TangDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0003-1200-0270
Andrew D JohnsonThe Framingham Heart Study, National Heart Lung and Blood Institute, Framingham, Massachusetts, USA.ORCID 0000-0001-6369-5178
University of Copenhagen · DKNational Heart Lung and Blood Institute · USJohns Hopkins University · USUCLA Medical Center · USUniversity of Minnesota · USHeidelberg University · DEKarolinska University Hospital · SENational Institutes of Health · USUniversity of Washington · USInserm · FRThe University of Texas Health Science Center at Houston · USUniversity of Michigan · USUniversity of Vermont · USFrederiksberg Hospital · DKHospital de Sant Pau · ESKaiser Permanente Washington Health Research Institute · USUnited States Department of Veterans Affairs · USUniversité de Bordeaux · FRUniversity of North Carolina at Chapel Hill · USUniversity of Oxford · GB
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI MARSH, LAURA · 1985 to 2007
$37.3MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MCardiovascular Genomics and Bioinformatics projectsZIAHL006170 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI JOHNSON, ANDREW · 2013 to 2025
$25.3MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MHHS HHSN268201700001IHHS HHSN268201700002IHHS HHSN268201700003IHHS HHSN268201700004IHHS HHSN268201700005IIntramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006170NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCATS NIH HHS UL1TR001881NCRR NIH HHS M01 RR000052NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N01HC8508NHLBI NIH HHS N02 HL064278NHLBI NIH HHS N02-HL-64278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL059684NHLBI NIH HHS R01 HL068986NHLBI NIH HHS R01HL068986NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01HL105756NHLBI NIH HHS R01 HL112064NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01HL120393NHLBI NIH HHS R01 HL134894NHLBI NIH HHS R01 HL139553NHLBI NIH HHS R01 HL141399NHLBI NIH HHS R35 HL135793NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NHLBI NIH HHS U01 HL130114NHLBI NIH HHS U01HL130114NHLBI NIH HHS UCLA CTSI UL1-TR001881NIA NIH HHS R01 AG023629NIDDK NIH HHS P30 DK063491NIH HHSNIH HHS 5RC2HL102419NIH HHS M01 RR00052
Abstract
backgroundUse of targeted exome-arrays with common, rare variants and functionally enriched variation has led to discovery of new genes contributing to population variation in risk factors. Plasminogen activator-inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and the plasma product D-dimer are important components of the fibrinolytic system. There have been few large-scale genome-wide or exome-wide studies of PAI-1, tPA, and D-dimer.
objectivesWe sought to discover new genetic loci contributing to variation in these traits using an exome-array approach.
methodsCohort-level analyses and fixed effects meta-analyses of PAI-1 (n = 15 603), tPA (n = 6876,) and D-dimer (n = 19 306) from 12 cohorts of European ancestry with diverse study design were conducted, including single-variant analyses and gene-based burden testing.
resultsFive variants located in NME7, FGL1, and the fibrinogen locus, all associated with D-dimer levels, achieved genome-wide significance (P < 5 × 10
conclusionThis work provides new evidence for a role of FGL1 in hemostasis.
Indexed as
Plasminogen Activator Inhibitor 1Tissue Plasminogen ActivatorExomeFibrin Fibrinogen Degradation ProductsFibrinogenFibrinolysisHumansFGL1 protein, humanFibrin Fibrinogen Degradation Productsfibrin fragment DFibrinogenPlasminogen Activator Inhibitor 1Tissue Plasminogen Activatorcomputational biologyexomefibrinogenfibrinolysisgenetic association study
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