Is there still room for additional common susceptibility alleles for venous thromboembolism?
Essentials Genetic architecture of venous thromboembolism (VTE) remains to be fully disentangled. 11 newly discovered candidate polymorphisms were genotyped in 3019 VTE cases and 2605 controls. None of the 11 polymorphisms were significantly associated with VTE risk. Additional major efforts are needed to identify VTE-associated genetic variants.



Background Through a meta-analysis of 12 genome-wide association studies, the International Network against VENous Thrombosis (INVENT) consortium identified two novel susceptibility loci for venous thromboembolism (VTE). This project has also generated other candidates that need to be confirmed. Objectives To assess the association with VTE of common single-nucleotide polymorphisms (SNPs) that demonstrated strong statistical, but not genome-wide, significance in the INVENT cohorts. Patients/methods Eleven SNPs were genotyped and tested for association with VTE in three case-control studies totaling 3019 patients and 2605 healthy individuals. Results and conclusions None of the tested SNPs showed evidence for association with VTE. Different strategies are needed to decipher the whole spectrum of common and rare genetic variations associated with VTE risk.
Team Genomics & Pathophysiology of Cardiovascular Diseases, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Sorbonne Universités, Paris, France. david.tregouet@upmc.fr.|ICAN Institute for Cardiometabolism and Nutrition, Paris, France. david.tregouet@upmc.fr.
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Trégouët
EA3878 and CIC1412, Université de Brest, Brest, France.
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Delluc
Service de Pneumologie et soins intensifs respiratoires, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, France.|Inserm UMR-S1140, Paris, France.
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Roche
Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
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Derbois
Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
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Olaso
Team Genomics & Pathophysiology of Cardiovascular Diseases, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Sorbonne Universités, Paris, France.|ICAN Institute for Cardiometabolism and Nutrition, Paris, France.
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Germain
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
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de Andrade
Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
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Tang
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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Chasman
Department of Thrombosis and Hemostasis, Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
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van Hylckama Vlieg
Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
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Reitsma
Department of Emergency Medicine, Massachusetts General Hospital, Channing Network Medicine, Harvard Medical School, Boston, MA, USA.
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Kabrhel
Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.|Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA, USA.
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Smith
Laboratory of Haematology, La Timone Hospital, Marseille, France.|Unité Mixte de Recherche en Santé (UMR_S) 1062, Nutrition Obesity and Risk of Thrombosis, Institut National pour la Santé et la Recherche Médicale (INSERM), Aix-Marseille University, Marseille, France.
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D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005602:France; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000235:genetics* / Q000628:therapy*; D055815:Young Adult
genetic polymorphisms; genome-wide association study; meta-analysis; risk factors; venous thromboembolism