Genome-wide association study in a Lebanese cohort confirms PHACTR1 as a major determinant of coronary artery stenosis.
Hager J., Kamatani Y., Cazier JB., Youhanna S., Ghassibe-Sabbagh M., Platt DE., Abchee AB., Romanos J., Khazen G., Othman R., Badro DA., Haber M., Salloum AK., Douaihy B., Shasha N., Kabbani S., Sbeite H., Chammas E., el Bayeh H., Rousseau F., Zelenika D., Gut I., Lathrop M., Farrall M., Gauguier D., Zalloua PA., FGENTCARD Consortium None.
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.