Exists a pharmacophoric approach was followed which combines three-dimensional information

Recurrence risk of VT is about 6% a year, and post-thrombotic MK-4827 PARP inhibitor disease occurs within the next 5 years following a VT event in about 25% of patients . It has been reported that 25,000 individuals die from the consequences of VT each year in England and that the disease has a substantial economic costs . Despite these striking elements, venous thrombosis can be considered as the Cinderella of genetic research on thrombotic disorders compared to arterial and cerebral thrombosis. Even though genetic factors are estimated to explain up to 60% of the VT heritability , VT genetics has not benefit a lot from the genome wide association study revolution. While several GWAS and meta-analysis of GWAS have been conducted for arterial and cerebral thrombosis on thousands of individuals , only one GWAS on VT has been reported so far , and on a rather small sample of 419 cases and 1,228 controls. Before this GWAS was carried out, well-established susceptibility genes for VT were SERPINC1, PROC, PROS1, FII, FGG, FV and ABO . The latter two loci were the only genomic regions that reached genome-wide statistical significance in the VT GWAS. Nevertheless, using additional strategies to assess the most promising associations generated by this GWAS, other VTassociated loci were robustly identified, HIVEP1 , C4BPA , and TC2N . Two additional VT-associated loci, GP6 and F11 , were also robustly identified through another large-scale association study, focusing mainly on non-synonymous polymorphisms. In our quest to identify novel susceptibility genes for VT beyond those already known , we report the results of a second GWAS based on a larger sample size and exploring a larger number of single nucleotide polymorphisms . The overall sequential procedure of this work was summarized in Figure 2. A standard GWAS comparing VT patients 1222998-36-8 participating in the MARTHA project to healthy individuals from the Three-City Study was first performed to identify genome-wide significant associations of SNPs with VT risk . Second, results from this GWAS were combined to those of our previously published GWAS on VT to detect novel associations that would not have been declared significant at stage I.

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