TY - JOUR
T1 - Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis
AU - Hager, Jörg
AU - Kamatani, Yoichiro
AU - Cazier, Jean-Baptiste
AU - Youhanna, Sonia
AU - Ghassibe-Sabbagh, Michella
AU - Platt, Daniel E
AU - Abchee, Antoine B
AU - Romanos, Jihane
AU - Khazen, Georges
AU - Othman, Raed
AU - Badro, Danielle A
AU - Haber, Marc
AU - Salloum, Angelique K
AU - Douaihy, Bouchra
AU - Shasha, Nabil
AU - Kabbani, Samer
AU - Sbeite, Hana
AU - Chammas, Elie
AU - el Bayeh, Hamid
AU - Rousseau, Francis
AU - Zelenika, Diana
AU - Gut, Ivo
AU - Lathrop, Mark
AU - Farrall, Martin
AU - Gauguier, Dominique
AU - Zalloua, Pierre A
AU - FGENTCARD Consortium
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Coronary Stenosis
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Lebanon
KW - Microfilament Proteins
KW - Polymorphism, Single Nucleotide
U2 - 10.1371/journal.pone.0038663
DO - 10.1371/journal.pone.0038663
M3 - Article
C2 - 22745674
SN - 1932-6203
VL - 7
SP - e38663
JO - PLoS ONE
JF - PLoS ONE
IS - 6
ER -