title: Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis.
abstract: 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.
authors: CEA-Genomics Institute, Centre National de Génotypage, Evry, France.
authors: Jörg
authors: J
authors: Hager
authors: Yoichiro
authors: Y
authors: Kamatani
authors: Jean-Baptiste
authors: JB
authors: Cazier
authors: Sonia
authors: S
authors: Youhanna
authors: Michella
authors: M
authors: Ghassibe-Sabbagh
authors: Daniel E
authors: DE
authors: Platt
authors: Antoine B
authors: AB
authors: Abchee
authors: Jihane
authors: J
authors: Romanos
authors: Georges
authors: G
authors: Khazen
authors: Raed
authors: R
authors: Othman
authors: Danielle A
authors: DA
authors: Badro
authors: Marc
authors: M
authors: Haber
authors: Angelique K
authors: AK
authors: Salloum
authors: Bouchra
authors: B
authors: Douaihy
authors: Nabil
authors: N
authors: Shasha
authors: Samer
authors: S
authors: Kabbani
authors: Hana
authors: H
authors: Sbeite
authors: Elie
authors: E
authors: Chammas
authors: Hamid
authors: H
authors: el Bayeh
authors: Francis
authors: F
authors: Rousseau
authors: Diana
authors: D
authors: Zelenika
authors: Ivo
authors: I
authors: Gut
authors: Mark
authors: M
authors: Lathrop
authors: Martin
authors: M
authors: Farrall
authors: Dominique
authors: D
authors: Gauguier
authors: Pierre A
authors: PA
authors: Zalloua
mesh_terms: D023921:Coronary Stenosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D007861:Lebanon; D008840:Microfilament Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008840:Microfilament Proteins; C570134:PHACTR1 protein, human