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.
PY - 2012/6/20
Y1 - 2012/6/20
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.
UR - http://www.scopus.com/inward/record.url?scp=84862682331&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0038663
DO - 10.1371/journal.pone.0038663
M3 - Article
C2 - 22745674
AN - SCOPUS:84862682331
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e38663
ER -
