Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis
| Autor: | Dominique Gauguier, Pierre Zalloua, Francis Rousseau, Hana Sbeite, Daniel E. Platt, Antoine Abchee, Jihane Romanos, Danielle A. Badro, Ivo Gut, Michella Ghassibe-Sabbagh, Marc Haber, Angelique K. Salloum, Elie Chammas, Georges Khazen, Nabil Shasha, Jörg Hager, Jean-Baptiste Cazier, Bouchra Douaihy, Hamid el Bayeh, Sonia Youhanna, Raed Othman, Yoichiro Kamatani, Mark Lathrop, Diana Zelenika, Martin Farrall, Samer Kabbani |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Genetic Screens
medicine.medical_treatment lcsh:Medicine Genome-wide association study 030204 cardiovascular system & hematology Bioinformatics Cardiovascular Coronary artery disease 0302 clinical medicine Lebanon lcsh:Science Cardiac catheterization 0303 health sciences education.field_of_study Multidisciplinary Microfilament Proteins Genomics 3. Good health medicine.anatomical_structure Medicine Research Article Genotype Clinical Research Design Population Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Molecular Genetics 03 medical and health sciences Genome Analysis Tools Genetic Mutation medicine Genome-Wide Association Studies Genetics Humans Genetic Predisposition to Disease education 030304 developmental biology Genetic association Clinical Genetics Arterial stenosis lcsh:R Coronary Stenosis Computational Biology Human Genetics medicine.disease Coronary arteries Genetics of Disease lcsh:Q Population Genetics Genome-Wide Association Study |
| Zdroj: | PLoS ONE, Vol 7, Iss 6, p e38663 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The manifestation of coronary artery disease (CAD) follows a well-choreographed series of events that includes damage of arterial endothelial cells and deposition of lipids in the sub-endothelial layers. Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are a crucial step in understanding global CAD pathophysiology. In this study, we report a GWAS on the genetic basis of arterial stenosis as measured by cardiac catheterization in a Lebanese population. The locus of the phosphatase and actin regulator 1 gene (PHACTR1) showed association with coronary stenosis in a discovery experiment with genome wide data in 1,949 individuals (rs9349379, OR = 1.37, p = 1.57×10(-5)). The association was replicated in an additional 2,547 individuals (OR = 1.31, p = 8.85×10(-6)), leading to genome-wide significant association in a combined analysis (OR = 1.34, p = 8.02×10(-10)). Results from this GWAS support a central role of PHACTR1 in CAD susceptibility irrespective of lifestyle and ethnic divergences. This association provides a plausible component for understanding molecular mechanisms involved in the formation of stenosis in cardiac vessels and a potential drug target against CAD. |
| Databáze: | OpenAIRE |
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