Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
, 14, 36

A Genome-Wide Search for Common SNP X SNP Interactions on the Risk of Venous Thrombosis

Affiliations
Meta-Analysis

A Genome-Wide Search for Common SNP X SNP Interactions on the Risk of Venous Thrombosis

Nicolas Greliche et al. BMC Med Genet.

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 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.

Similar articles

See all similar articles

Cited by 11 articles

See all "Cited by" articles

References

    1. White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107:I4–I8. - PubMed
    1. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999;353:1167–1173. doi: 10.1016/S0140-6736(98)10266-0. - DOI - PubMed
    1. Souto JC, Almasy L, Borrell M, Blanco-Vaca F, Mateo J, Soria JM, Coll I, Felices R, Stone W, Fontcuberta J, Blangero J. Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia. Am J Hum Genet. 2000;67:1452–1459. doi: 10.1086/316903. - DOI - PMC - PubMed
    1. Morange PE, Tregouet DA. Lessons from genome-wide association studies in venous thrombosis. J Thromb Haemost. 2011;9(Suppl 1):258–264. - PubMed
    1. Tregouet DA, Heath S, Saut N, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Juhan-Vague I. Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach. Blood. 2009;113:5298–5303. doi: 10.1182/blood-2008-11-190389. - DOI - PubMed

Publication types

Feedback