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

作者：Greliche Nicolas; Germain Marine; Lambert Jean Charles; Cohen William; Bertrand Marion; Dupuis Anne Marie; Letenneur Luc; Lathrop Mark; Amouyel Philippe; Morange Pierre Emmanuel; Tregouet David Alexandre^*

来源：BMC Medical Genetics, 2013, 14(1): 36.

DOI：10.1186/1471-2350-14-36

• Venous thrombosis
• Genome-Wide Association Study
• Interaction
• Factor VIII

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 similar to 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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2013-3-20