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

Greliche, Nicolas, Germain, Marine, Lambert, Jean-Charles, Cohen, William, Bertrand, Marion, Dupuis, Anne-Marie, Letenneur, Luc, Lathrop, Mark, Amouyel, Philippe, Morange, Pierre-Emmanuel, and Trégouët, David-Alexandre (2013) A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis. BMC Medical Genetics, 14 (36). pp. 1-7.

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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.

Item ID: 42931
Item Type: Article (Research - C1)
ISSN: 1471-2350
Keywords: Venous thrombosis; Genome-Wide Association Study; Interaction; Factor VIII
Additional Information:

© 2013 Greliche et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Funders: Fondation pour la Recherche Médicale (FRM), Région Ile de France, Pierre and Marie Curie University
Date Deposited: 23 Feb 2016 23:44
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 10%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 90%
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