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

Journal article

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=1.57x10(-5)). The association was replicated in an additional 2,547 individuals (OR=1.31, p=8.85x10(-6)), leading to genome-wide significant association in a combined analysis (OR=1.34, p=8.02x10(-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: Hager, J; Kamatani, Y; Cazier, J; Youhanna, S; Ghassibe-Sabbagh, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PloS one
• Volume: 7
• Issue: 6
• Article number: e38663
• Publication date: 2012-01-01
• DOI: 10.1371/journal.pone.0038663
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: Genome-Wide Association Study; Coronary Stenosis; Polymorphism, Single Nucleotide; Humans; Genotype; Lebanon; Genetic Predisposition to Disease; FGENTCARD Consortium; Microfilament Proteins