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

Autor: Jean-Charles Lambert, Marion Bertrand, William Cohen, Nicolas Greliche, Pierre-Emmanuel Morange, David-Alexandre Trégouët, Philippe Amouyel, Marine Germain, Mark Lathrop, Luc Letenneur, Anne-Marie Dupuis
Přispěvatelé: Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroépidémiologie, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Santé et Prévention, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Statistical analyses benefit from the C2BIG computing centre funded by the Fondation pour la Recherche Médicale, La Région Ile de France (CODDIM) and the Genomic Network of the Pierre and Marie Curie University (Paris 06)., Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), BMC, Ed.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Adult
Male
Interaction
Locus (genetics)
Genome-wide association study
Single-nucleotide polymorphism
[SDV.GEN] Life Sciences [q-bio]/Genetics
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
030204 cardiovascular system & hematology
Biology
Bioinformatics
Polymorphism
Single Nucleotide
White People
Génétique humaine
03 medical and health sciences
0302 clinical medicine
Human genetics
Genetic variation
Venous thrombosis
Odds Ratio
Genetics
Humans
SNP
Genetic Predisposition to Disease
Genetics(clinical)
Genetics (clinical)
Aged
030304 developmental biology
Homeodomain Proteins
0303 health sciences
[SDV.GEN]Life Sciences [q-bio]/Genetics
Factor VIII
Genome-Wide Association Study
Case-control study
Epistasis
Genetic
Odds ratio
Middle Aged
Heritability
3. Good health
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Case-Control Studies
Female
France
Research Article
Transcription Factors
Zdroj: BMC Medical Genetics
BMC Medical Genetics, BioMed Central, 2013, 14 (1), pp.36. ⟨10.1186/1471-2350-14-36⟩
www.biomedcentral.com/bmcmedgenet
BMC Medical Genetics, 2013, 14 (1), pp.36. ⟨10.1186/1471-2350-14-36⟩
BMC Medical Genetics 1 (14), . (2013)
ISSN: 1471-2350
DOI: 10.1186/1471-2350-14-36⟩
Popis: 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.
Databáze: OpenAIRE
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