Genetics of venous thrombosis: insights from a new genome wide association study

Germain, Marine, Saut, Noémie, Greliche, Nicolas, Dina, Christian, Lambert, Jean-Charles, Perret, Claire, Cohen, William, Oudot-Mellakh, Tiphaine, Antoni, Guillemette, Alessi, Marie-Christine, Zelenika, Diana, Cambien, François, Tiret, Laurance, Bertrand, Marion, Dupuy, Anne-Marie, Letenneur, Luc, Lathrop, Mark, Emmerich, Joseph, Amouyel, Philippe, Trégouët, David-Alexandre, and Morange, Pierre-Emmanuel (2011) Genetics of venous thrombosis: insights from a new genome wide association study. PLoS ONE, 6 (9). e25581. pp. 1-11.

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Abstract

Background: Venous Thrombosis (VT) is a common multifactorial disease associated with a major public health burden. Genetics factors are known to contribute to the susceptibility of the disease but how many genes are involved and their contribution to VT risk still remain obscure. We aimed to identify genetic variants associated with VT risk.

Methodology/Principal Findings: We conducted a genome-wide association study (GWAS) based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0×10−8 and encompassed four known VT-associated loci, ABO, F5, F11 and FGG. By means of haplotype analyses, we also provided novel arguments in favor of a role of HIVEP1, PROCR and STAB2, three loci recently hypothesized to participate in the susceptibility to VT. However, no novel VT-associated loci came out of our GWAS. Using a recently proposed statistical methodology, we also showed that common variants could explain about 35% of the genetic variance underlying VT susceptibility among which 3% could be attributable to the main identified VT loci. This analysis additionally suggested that the common variants left to be identified are not uniformly distributed across the genome and that chromosome 20, itself, could contribute to ∼7% of the total genetic variance.

Conclusions/Significance: This study might also provide a valuable source of information to expand our understanding of biological mechanisms regulating quantitative biomarkers for VT.

Item ID: 42930
Item Type: Article (Research - C1)
ISSN: 1932-6203
Keywords: venous thrombosis; genetic epidemiology; genome wide association study
Additional Information:

© 2011 Germain et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: Agence Nationale pour la Recherche (ANR), Program Hospitalier de Recherche Clinique (PHRC), Fondation pour la Recherche Médicale (FRM), Fondation de France, Leducq Foundation, La Région Ile de France, Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Generale de l'Education Nationale, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, Regional Governments of Aquitaine, Regional Governments of Bourgogne, Regional Governments of Languedoc-Roussillon, INSERM, Eisai, Sanofi-Synthélabo
Projects and Grants: Project ANR-07-MRAR-021, PHRC 2009 RENOVA-TV, PHRC 20002
Date Deposited: 23 Feb 2016 04:02
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 30%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 70%
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