Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis

View/ Open
Author
Hager, Jörg
Kamatani, Yoichiro
Cazier, Jean-Baptiste
Youhanna, Sonia
Ghassibe-Sabbagh, Michella
Platt, Daniel E.
Abchee, Antoine B.
Romanos, Jihane
Khazen, Georges
Othman, Raed
Badro, Danielle A.
Haber, Marc
Salloum, Angelique K.
Douaihy, Bouchra
Shasha, Nabil
Kabbani, Samer
Sbeite, Hana
Chammas, Elie
el Bayeh, Hamid
Rousseau, Francis
Zelenika, Diana
Gut, Ivo
Lathrop, Mark
Farrall, Martin
Gauguier, Dominique
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pone.0038663Metadata
Show full item recordCitation
Hager, Jörg, Yoichiro Kamatani, Jean-Baptiste Cazier, Sonia Youhanna, Michella Ghassibe-Sabbagh, Daniel E. Platt, Antoine B. Abchee,et al. 2012. Genome-wide association study in a lebanese cohort confirms phactr1 as a major determinant of coronary artery stenosis. PLoS ONE 7(6): e38663.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380020/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10497276
Collections
- SPH Scholarly Articles [4830]
Contact administrator regarding this item (to report mistakes or request changes)