Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis

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 life...

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Published in:PloS one 2012-06, Vol.7 (6), p.e38663-e38663
Main Authors: Hager, Jörg, Kamatani, Yoichiro, Cazier, Jean-Baptiste, Youhanna, Sonia, Ghassibe-Sabbagh, Michella, Platt, Daniel E, Abchee, Antoine B, Romanos, Jihane, Khazen, Georges, Othman, Raed, Badro, Danielle A, Haber, Marc, Salloum, Angelique K, Douaihy, Bouchra, Shasha, Nabil, Kabbani, Samer, Sbeite, Hana, Chammas, Elie, el Bayeh, Hamid, Rousseau, Francis, Zelenika, Diana, Gut, Ivo, Lathrop, Mark, Farrall, Martin, Gauguier, Dominique, Zalloua, Pierre A
Format: Article
Language:English
Subjects:
Actin
Angina pectoris
Atherosclerosis
Bioinformatics
Biology
Blood vessels
Cardiology
Cardiovascular disease
Catheterization
Chromosomes
Consortia
Coronary artery
Coronary artery disease
Coronary Stenosis - genetics
Coronary vessels
Endothelial cells
Family medical history
Genes
Genetic aspects
Genetic Predisposition to Disease - genetics
Genetics
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genomics
Genotype
Heart
Heart diseases
Heart failure
Humans
Intubation
Ischemia
Lebanon
Lifestyles
Lipids
Medicine
Microfilament Proteins - genetics
Molecular modelling
Phosphatase
Phosphatases
Phosphorylation
Polymorphism, Single Nucleotide - genetics
Population
Population genetics
Principal components analysis
Risk factors
Stenosis
Studies
Tomography
Type 2 diabetes
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0038663