Is there still room for additional common susceptibility alleles for venous thromboembolism?

D A Trégouët; A Delluc; A Roche; C Derbois; R Olaso; M Germain; M de Andrade; W Tang; D I Chasman; A van Hylckama Vlieg; P H Reitsma; C Kabrhel; N Smith; P E Morange

doi:10.1111/jth.13392

Is there still room for additional common susceptibility alleles for venous thromboembolism?

J Thromb Haemost. 2016 Sep;14(9):1798-802. doi: 10.1111/jth.13392. Epub 2016 Aug 6.

Authors

D A Trégouët^{1

2}, A Delluc³, A Roche^{4

5

6}, C Derbois⁷, R Olaso⁷, M Germain^{8

9}, M de Andrade¹⁰, W Tang¹¹, D I Chasman¹², A van Hylckama Vlieg¹³, P H Reitsma¹⁴, C Kabrhel¹⁵, N Smith^{16

17

18}, P E Morange^{19

20}

Affiliations

¹ Team Genomics & Pathophysiology of Cardiovascular Diseases, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Sorbonne Universités, Paris, France. david.tregouet@upmc.fr.
² ICAN Institute for Cardiometabolism and Nutrition, Paris, France. david.tregouet@upmc.fr.
³ EA3878 and CIC1412, Université de Brest, Brest, France.
⁴ Service de Pneumologie et soins intensifs respiratoires, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
⁵ Université Paris Descartes, Sorbonne Paris Cité, France.
⁶ Inserm UMR-S1140, Paris, France.
⁷ Centre National de Génotypage, Institut de Génomique, CEA, Evry, France.
⁸ Team Genomics & Pathophysiology of Cardiovascular Diseases, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Sorbonne Universités, Paris, France.
⁹ ICAN Institute for Cardiometabolism and Nutrition, Paris, France.
¹⁰ Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
¹¹ Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA.
¹² Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹³ Department of Thrombosis and Hemostasis, Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
¹⁴ Einthoven Laboratory for Experimental Vascular Medicine, Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
¹⁵ Department of Emergency Medicine, Massachusetts General Hospital, Channing Network Medicine, Harvard Medical School, Boston, MA, USA.
¹⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁷ Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
¹⁸ Seattle Epidemiologic Research and Information Center, VA Office of Research and Development, Seattle, WA, USA.
¹⁹ Laboratory of Haematology, La Timone Hospital, Marseille, France.
²⁰ 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.

Abstract

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.

Summary: 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.

Keywords: genetic polymorphisms; genome-wide association study; meta-analysis; risk factors; venous thromboembolism.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Alleles*
Case-Control Studies
Female
France
Genetic Predisposition to Disease*
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Regression Analysis
Risk Factors
Venous Thromboembolism / genetics*
Venous Thromboembolism / therapy*
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding