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

Abstract : Background
Venous 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.
Methods
A 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.
Results
The 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.
Conclusion
This 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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https://www.hal.inserm.fr/inserm-00804327
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Submitted on : Monday, March 25, 2013 - 1:07:04 PM
Last modification on : Friday, May 29, 2020 - 7:50:37 AM
Long-term archiving on: : Wednesday, June 26, 2013 - 4:02:05 AM

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Citation

Nicolas Greliche, Marine Germain, Jean-Charles Lambert, William Cohen, Marion Bertrand, et al.. A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis. BMC Medical Genetics, BioMed Central, 2013, 14 (1), pp.36. ⟨10.1186/1471-2350-14-36⟩. ⟨inserm-00804327⟩

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