SynthesisAmerican journal of human genetics2015
Meta-analysis of 65,734 individuals identifies TSPAN15 and SLC44A2 as two susceptibility loci for venous thromboembolism.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 11 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 11 pooled it
21.8field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
147 citing papers in PubMed, 11 syntheses or guidelines pooled it, 270 citations in OpenAlex.
- GP6 polymorphisms and venous thromboembolism: a Chinese case-control study with cross-population assessment.BMC cardiovascular disorders · 2026Pooled it
- Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism.Blood advances · 2023Pooled it
- Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.BMC medicine · 2023Pooled it
- Thrombophilia testing: A British Society for Haematology guideline.British journal of haematology · 2022Guideline
- Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.European heart journal · 2021Pooled it
- Association of ABO polymorphisms and pancreatic Cancer/ Cardiocerebrovascular disease: a meta-analysis.BMC medical genetics · 2020Pooled it
- Burden of rare exome sequence variants in PROC gene is associated with venous thromboembolism: a population-based study.Journal of thrombosis and haemostasis : JTH · 2020Pooled it
- A large-scale exome array analysis of venous thromboembolism.Genetic epidemiology · 2019Pooled it
- Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels.Circulation · 2019Pooled it
- Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.Nature genetics · 2018Pooled it
- Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism.Journal of thrombosis and haemostasis : JTH · 2016Pooled it
- Trial
- Genetic Analysis of Venous Thromboembolism in UK Biobank Identifies the ZFPM2 Locus and Implicates Obesity as a Causal Risk Factor.Circulation. Cardiovascular genetics · 2017Trial
- Assessing genetic risk factors for early-onset coronary artery disease in Iranians.Research and practice in thrombosis and haemostasis · 2026Article
- Polygenic risk scores: Navigating the future of precision medicine through economic, ethical, and scientific advancements.iScience · 2026Review
- Genetic risk assessment of pregnancy-associated venous thromboembolism: dual utility of maternal peripheral blood in NIPT and VTE evaluation.BMC pregnancy and childbirth · 2026Article
- Development of a MassARRAY Genotyping Platform and Its Clinical Application for Venous Thromboembolism Risk Assessment in Thai Patients.Medical sciences (Basel, Switzerland) · 2025Article
- Discovery of a Novel Anticoagulant Cystine Knot Peptide from Spider Venom Gland Transcriptome.International journal of molecular sciences · 2025Article
- Multipopulation GWAS for venous thromboembolism identifies novel loci followed by experimental validation in zebrafish.Blood advances · 2025Article
- Altered DNA methylation of the ABO gene is associated with differential plasma levels of von willebrand factor and E-selectin.Transfusion · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
51 authors at 20 institutions in 8 countries.
Marine GermainInstitut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, 75013 Paris, France; Institute for Cardiometabolism and Nutrition (ICAN), 75013 Paris, France.
Daniel I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Hugoline de HaanDepartment of Thrombosis and Hemostasis, Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Weihong TangDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA.
Sara LindströmProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Lu-Chen WengDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA.
Mariza de AndradeDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
Marieke C H de VisserEinthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Kerri L WigginsDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA.
Pierre SuchonLaboratory of Haematology, La Timone Hospital, 13385 Marseille, France; INSERM, UMR_S 1062, Nutrition Obesity and Risk of Thrombosis, 13385 Marseille, France; Nutrition Obesity and Risk of Thrombosis, Aix-Marseille University, UMR_S 1062, 13385 Marseille, France.
Noémie SautLaboratory of Haematology, La Timone Hospital, 13385 Marseille, France; INSERM, UMR_S 1062, Nutrition Obesity and Risk of Thrombosis, 13385 Marseille, France; Nutrition Obesity and Risk of Thrombosis, Aix-Marseille University, UMR_S 1062, 13385 Marseille, France.
David M SmadjaUniversité Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France; AP-HP, Hopital Européen Georges Pompidou, Service d'Hématologie Biologique, 75015 Paris, France; Faculté de Pharmacie, INSERM, UMR_S 1140, 75006 Paris, France.
Grégoire Le GalUniversité de Brest, EA3878 and CIC1412, 29238 Brest, France; Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, ON K1Y 4E9, Canada.
Astrid van Hylckama VliegDepartment of Thrombosis and Hemostasis, Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Antonio Di NarzoDepartment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ke HaoDepartment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
Christopher P NelsonDepartment of Cardiovascular Sciences, University of Leicester, LE1 7RH Leicester, UK; National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UK.
Ares Rocanin-ArjoInstitut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, 75013 Paris, France; Institute for Cardiometabolism and Nutrition (ICAN), 75013 Paris, France.
Lasse FolkersenDepartment of PharmacoGenetics, Novo Nordisk Park 9.1.21, 2400 Copenhagen, Denmark.
Ramin MonajemiDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Lynda M RoseDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA 98195-5852, USA.
Eline SlagboomDepartment of Molecular Epidemiology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Dylan AïssiInstitut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, 75013 Paris, France; Institute for Cardiometabolism and Nutrition (ICAN), 75013 Paris, France.
France GagnonDivision of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada.
Jean-Francois DeleuzeCommissariat à l'Energie Atomique/Direction des Sciences du Vivant/Institut de Génomique, Centre National de Génotypage, 91057 Evry, France.
Panos DeloukasWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 4NS, UK; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Christophe TzourioInserm Research Center U897, University of Bordeaux, 33000 Bordeaux, France.
Jean-Francois DartiguesInserm Research Center U897, University of Bordeaux, 33000 Bordeaux, France.
Claudine BerrInserm Research Unit U1061, University of Montpellier I, 34000 Montpellier, France.
Kent D TaylorLos Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrence, CA 90502, USA.
Mete CivelekDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Per ErikssonAtherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cardiogenics Consortium
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA 98195-5852, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA.
Jeanine Houwing-DuitermaatDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
Alison H GoodallDepartment of Cardiovascular Sciences, University of Leicester, LE1 7RH Leicester, UK; National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UK.
François CambienInstitut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, 75013 Paris, France; Institute for Cardiometabolism and Nutrition (ICAN), 75013 Paris, France.
Peter KraftProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Philippe AmouyelInstitut Pasteur de Lille, Université de Lille Nord de France, INSERM UMR_S 744, 59000 Lille, France; Centre Hospitalier Régional Universitaire de Lille, 59000 Lille, France.
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, LE1 7RH Leicester, UK; National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UK.
Saonli BasuDivision of Biostatistics, University of Minnesota, Minneapolis, MN 55455, USA.
Paul M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
Frits R RosendaalDepartment of Thrombosis and Hemostasis, Department of Clinical Epidemiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Christopher KabrhelDepartment of Emergency Medicine, Massachusetts General Hospital, Channing Network Medicine, Harvard Medical School, Boston, MA 2114, USA.
Aaron R FolsomDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55454, USA.
John HeitDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Pieter H ReitsmaEinthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, 2300 RC Leiden, the Netherlands.
David-Alexandre TrégouëtInstitut National pour la Santé et la Recherche Médicale (INSERM), Unité Mixte de Recherche en Santé (UMR_S) 1166, 75013 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, 75013 Paris, France; Institute for Cardiometabolism and Nutrition (ICAN), 75013 Paris, France.
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA 98195, USA; Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA; Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA 98108, USA. Electronic address: nlsmith@u.washington.edu.
Pierre-Emmanuel MorangeLaboratory of Haematology, La Timone Hospital, 13385 Marseille, France; INSERM, UMR_S 1062, Nutrition Obesity and Risk of Thrombosis, 13385 Marseille, France; Nutrition Obesity and Risk of Thrombosis, Aix-Marseille University, UMR_S 1062, 13385 Marseille, France. Electronic address: pierre.morange@ap-hm.fr.
Leiden University Medical Center · NLInserm · FRUniversity of Minnesota · USFondation pour l’innovation en Cadiométabolisme et Nutrition · FRHarvard University · USUniversity of Washington · USBrigham and Women's Hospital · USIcahn School of Medicine at Mount Sinai · USUniversity of Leicester · GBCentre Hospitalier Universitaire de Lille · FRCommissariat à l'Énergie Atomique et aux Énergies Alternatives · FRHôpital de la Timone · FRKaiser Permanente Washington Health Research Institute · USKarolinska Institutet · SEKing Abdulaziz University · SAMassachusetts General Hospital · USMayo Clinic · USMayo Clinic in Arizona · USNational Institute for Health Research · GBNovo Nordisk (Denmark) · DK
Funding
UCLA 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
$11.8MGenome-wide case-only study of antihypertensive drug-gene interactionsR01HL085251 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2007 to 2010
$7.2MEstrogens and pharmacogenetic risks of venous thrombosis in postmenopausal womenR01HL073410 · NHLBI · UNIVERSITY OF WASHINGTON · PI SMITH, NICHOLAS L · 2004 to 2012
$4.8MThe 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
$4.0MAtrial Fibrillation: Incidence, Risk Factors, and GeneticsR01HL068986 · NHLBI · UNIVERSITY OF WASHINGTON · PI HECKBERT, SUSAN R · 2002 to 2010
$3.5MGenetic and Environmental Risk Factors for Venous ThromboembolismR01HL116854 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KABRHEL, CHRISTOPHER · 2013 to 2017
$3.4MCALCIUM-CHANNEL BLOCKERS AND PRIMARY PREVENTION OF CHDR01HL043201 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 1991 to 2004
$3.0MPharmacologic and pharmacogenetic associations with recurrent venous thrombosisR01HL095080 · NHLBI · UNIVERSITY OF WASHINGTON · PI SMITH, NICHOLAS L · 2008 to 2012
$2.9MPharmacogenetics and Cardiovascular EventsR01HL074745 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2003 to 2006
$2.8MHormone Replacement Therapy and Prothrombotic VariantsR01HL068639 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2002 to 2005
$1.9MCanadian Institutes of Health ResearchNCATS NIH HHS UL1 TR000124NCI NIH HHS UM1 CA182913NHLBI NIH HHS R01 HL043201NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL068639NHLBI NIH HHS R01 HL068986NHLBI NIH HHS R01 HL073410NHLBI NIH HHS R01 HL074745NHLBI NIH HHS R01 HL085251NHLBI NIH HHS R01 HL095080NHLBI NIH HHS R01 HL116854NIDDK NIH HHS P30 DK063491
Abstract
Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10(-8) including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10(-16)) and 1.21 (p = 2.75 × 10(-15)), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology.
Indexed as
Genetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeHumansMembrane GlycoproteinsMembrane Transport ProteinsOdds RatioTetraspaninsVenous ThromboembolismMembrane GlycoproteinsMembrane Transport ProteinsSLC44A2 protein, humanTetraspaninsTSPAN15 protein, human
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