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

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

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Title: Genome-Wide Association Study in a Lebanese Cohort Confirms PHACTR1 as a Major Determinant of Coronary Artery Stenosis
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; Zalloua, Pierre A.

Note: Order does not necessarily reflect citation order of authors.

Citation: 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.
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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.
Published Version: doi:10.1371/journal.pone.0038663
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#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10497276
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