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

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...

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Autores principales: Greliche, Nicolas, Germain, Marine, Lambert, Jean-Charles, Cohen, William, Bertrand, Marion, Dupuis, Anne-Marie, Letenneur, Luc, Lathrop, Mark, Amouyel, Philippe, Morange, Pierre-Emmanuel, Trégouët, David-Alexandre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607886/
https://www.ncbi.nlm.nih.gov/pubmed/23509962
http://dx.doi.org/10.1186/1471-2350-14-36
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author Greliche, Nicolas
Germain, Marine
Lambert, Jean-Charles
Cohen, William
Bertrand, Marion
Dupuis, Anne-Marie
Letenneur, Luc
Lathrop, Mark
Amouyel, Philippe
Morange, Pierre-Emmanuel
Trégouët, David-Alexandre
author_facet Greliche, Nicolas
Germain, Marine
Lambert, Jean-Charles
Cohen, William
Bertrand, Marion
Dupuis, Anne-Marie
Letenneur, Luc
Lathrop, Mark
Amouyel, Philippe
Morange, Pierre-Emmanuel
Trégouët, David-Alexandre
author_sort Greliche, Nicolas
collection PubMed
description 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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spelling pubmed-36078862013-03-27 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 Trégouët, David-Alexandre BMC Med Genet Research Article 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. BioMed Central 2013-03-20 /pmc/articles/PMC3607886/ /pubmed/23509962 http://dx.doi.org/10.1186/1471-2350-14-36 Text en Copyright ©2013 Greliche et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research Article
Greliche, Nicolas
Germain, Marine
Lambert, Jean-Charles
Cohen, William
Bertrand, Marion
Dupuis, Anne-Marie
Letenneur, Luc
Lathrop, Mark
Amouyel, Philippe
Morange, Pierre-Emmanuel
Trégouët, David-Alexandre
A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title_full A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title_fullStr A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title_full_unstemmed A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title_short A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis
title_sort genome-wide search for common snp x snp interactions on the risk of venous thrombosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3607886/
https://www.ncbi.nlm.nih.gov/pubmed/23509962
http://dx.doi.org/10.1186/1471-2350-14-36
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