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PLoS By Category | Recent PLoS Articles
Hematology

Genetics of Venous Thrombosis: Insights from a New Genome Wide Association Study
Published: Tuesday, September 27, 2011
Author: Marine Germain et al.

by Marine Germain, Noémie Saut, Nicolas Greliche, Christian Dina, Jean-Charles Lambert, Claire Perret, William Cohen, Tiphaine Oudot-Mellakh, Guillemette Antoni, Marie-Christine Alessi, Diana Zelenika, François Cambien, Laurence Tiret, Marion Bertrand, Anne-Marie Dupuy, Luc Letenneur, Mark Lathrop, Joseph Emmerich, Philippe Amouyel, David-Alexandre Trégouët, Pierre-Emmanuel Morange

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.

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