Large scale association analysis identifies three susceptibility loci for coronary artery disease

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dc.contributor.author El-Khazen, Georges
dc.contributor.author Zalloua, Pierre A.
dc.contributor.author Saade, Stephanie
dc.contributor.author Cazier, Jean-Baptiste
dc.contributor.author Ghassibe-Sabbagh, Michella
dc.contributor.author Youhanna, Sonia
dc.contributor.author Badro, Danielle A.
dc.contributor.author Kamatani, Yoichiro
dc.date.accessioned 2016-03-17T11:51:20Z
dc.date.available 2016-03-17T11:51:20Z
dc.date.copyright 2011
dc.date.issued 2016-03-17
dc.identifier.uri http://hdl.handle.net/10725/3353
dc.description.abstract Genome wide association studies (GWAS) and their replications that have associated DNA variants with myocardial infarction (MI) and/or coronary artery disease (CAD) are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3), and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR = 0.68, p = 0.0035), while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR = 1.33, p = 0.0086). Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology. en_US
dc.language.iso en en_US
dc.title Large scale association analysis identifies three susceptibility loci for coronary artery disease en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201105253 en_US
dc.author.idnumber 200300001 en_US
dc.author.idnumber 201101727 en_US
dc.author.idnumber 201101727 en_US
dc.author.woa N/A en_US
dc.author.department Computer Science and Mathematics en_US
dc.description.embargo N/A en_US
dc.relation.journal PLOS One en_US
dc.journal.volume 6 en_US
dc.journal.issue 12 en_US
dc.article.pages 1-7 en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0029427 en_US
dc.identifier.ctation Saade, S., Cazier, J. B., Ghassibe-Sabbagh, M., Youhanna, S., Badro, D. A., Kamatani, Y., ... & Salloum, A. K. (2011). Large scale association analysis identifies three susceptibility loci for coronary artery disease. PloS one, 6(12), e29427. en_US
dc.author.email GKhazen@lau.edu.lb
dc.author.email pierre.zalloua@lau.edu.lb
dc.author.email michella.sabbagh@lau.edu.lb en_US
dc.chapter.email michella.sabbagh@lau.edu.lb en_US
dc.identifier.url http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029427
dc.orcid.id https://orcid.org/0000-0002-8494-5081 en_US
dc.orcid.id https://orcid.org/0000-0003-2107-9929 en_US

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