[No authors listed]
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 10(10). 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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FAM155A-IT1, GNA14-AS1, LOC102723686, DLC1, NEBL, CHRM3, MGLL, PCMTD1, WDR63, OLFML2A, FBXO15, AK4, EFEMP1, FGF14, ZC3H3, NAALADL2, FGF14-IT1, LINC00877, GRIN2A, BRWD1, UQCC1, LYRM4, PAPPA2, RORA, PIEZO2, ARHGEF28, GSG1L2, SGK1, SMIM23, FAM228A, SOX5, SURF6, TAF4B, TBX5, FAM155A, LOC728755, YEATS4, RSAD2, PLXNA4, GNA14, RAB11FIP3
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