Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels

Antoni, Guillemette; Oudot-Mellakh, Tiphaine; Dimitromanolakis, Apostolos; Germain, Marine; Cohen, William; Wells, Philip S.; Lathrop, Mark; Morange, Pierre‐Emmanuel; Trégouët, David‐Alexandre

doi:10.1186/1471-2350-12-102

Cited by 62 publications

(33 citation statements)

References 32 publications

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“…The MARTHA study is a collection of 1,542 patients with venous thrombosis (VT) recruited from the Thrombophilia centre of La Timone hospital (Marseille, France) 169,170,171,172 . All subjects had a documented history of VT, were free of chronic diseases, and were free of inherited thrombophilia including: anti-thrombin, protein C and protein S deficiencies and homozygosity for the Factor V Leiden and Factor II G20210A mutations.…”

Section: The Martha Cohortmentioning

confidence: 99%

SASH1, a new potential link between smoking and atherosclerosis

et al. 2015

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Section: The Martha Cohortmentioning

confidence: 99%

SASH1, a new potential link between smoking and atherosclerosis

et al. 2015

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“…We found positive associations with rs732505, 19 identified in a combined analysis of two GWAS reports of vWF (Table 3). Furthermore, we replicated vWF associations in ADAMTS13 , (rs4962153, p = 5.54×10 -8 ), OBP2B (rs11244035, p = 2.33 × 10 -6 ), C9orf96 (rs28602591, p = 1.52 × 10 -4 ), and vWF (rs1063856, p =5.26×10 -6 ) 20 (Table 3; a priori Bonferroni corrected significance threshold p = 6.25 × 10 -3 ).…”

Section: Resultsmentioning

confidence: 70%

“…19–21 The EuroCLOT study identified this same SNP as associated with vWF, stroke, large vessel, and cardioembolic stroke. 18 Additional ABO SNPs have been associated with vascular outcomes including venous thromboembolism, ischemic stroke, and coronary heart disease (Table 3) (Supplemental Table III) indicating a major role for this gene in the pathophysiology of vascular disease.…”

Section: Discussionmentioning

confidence: 99%

Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke

Williams

Hsu

Keene

et al. 2017

Stroke

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Background and Purpose von Willebrand Factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. Methods We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the Vitamin Intervention for Stroke Prevention (VISP) trial as well as the utility of vWF in reclassification over traditional factors. We conducted a genome-wide association study (GWAS) with imputation, based upon 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus (eQTL) analysis for vWF across different tissues. Results Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified SNPs significantly associated with circulating vWF at the ABO locus (p < 5×10-8) and replicated findings from previous genetic associations of vWF levels in humans. eQTL analyses demonstrate that most associated ABO SNPs were also associated with vWF gene expression. Conclusions Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk, and may have implications for clinical care decision-making.

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“…These two studies have already been extensively described in [5,6,14] for EOVT and in [6,15-17] for MARTHA.…”

Section: Methodsmentioning

confidence: 99%

A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis

et al. 2013

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BackgroundVenous Thrombosis (VT) is a common multifactorial disease with an estimated heritability between 35% and 60%. Known genetic polymorphisms identified so far only explain ~5% of the genetic variance of the disease. This study was aimed to investigate whether pair-wise interactions between common single nucleotide polymorphisms (SNPs) could exist and modulate the risk of VT.MethodsA genome-wide SNP x SNP interaction analysis on VT risk was conducted in a French case–control study and the most significant findings were tested for replication in a second independent French case–control sample. The results obtained in the two studies totaling 1,953 cases and 2,338 healthy subjects were combined into a meta-analysis.ResultsThe smallest observed p-value for interaction was p = 6.00 10-11 but it did not pass the Bonferroni significance threshold of 1.69 10-12 correcting for the number of investigated interactions that was 2.96 1010. Among the 37 suggestive pair-wise interactions with p-value less than 10-8, one was further shown to involve two SNPs, rs9804128 (IGFS21 locus) and rs4784379 (IRX3 locus) that demonstrated significant interactive effects (p = 4.83 10-5) on the variability of plasma Factor VIII levels, a quantitative biomarker of VT risk, in a sample of 1,091 VT patients.ConclusionThis study, the first genome-wide SNP interaction analysis conducted so far on VT risk, suggests that common SNPs are unlikely exerting strong interactive effects on the risk of disease.

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Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels

Cited by 62 publications

References 32 publications

SASH1, a new potential link between smoking and atherosclerosis

SASH1, a new potential link between smoking and atherosclerosis

Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke

A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis

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