Large scale association analysis identifies three susceptibility loci for coronary artery disease
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 polymorph...
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2011
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| Online Access: | http://hdl.handle.net/10725/3353 http://dx.doi.org/10.1371/journal.pone.0029427 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029427 |
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| _version_ | 1864513460999553024 |
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| author | El-Khazen, Georges |
| author2 | Zalloua, Pierre A. Saade, Stephanie Cazier, Jean-Baptiste Ghassibe-Sabbagh, Michella Youhanna, Sonia Badro, Danielle A. Kamatani, Yoichiro |
| author2_role | author author author author author author author |
| author_facet | El-Khazen, Georges Zalloua, Pierre A. Saade, Stephanie Cazier, Jean-Baptiste Ghassibe-Sabbagh, Michella Youhanna, Sonia Badro, Danielle A. Kamatani, Yoichiro |
| author_role | author |
| dc.creator.none.fl_str_mv | El-Khazen, Georges Zalloua, Pierre A. Saade, Stephanie Cazier, Jean-Baptiste Ghassibe-Sabbagh, Michella Youhanna, Sonia Badro, Danielle A. Kamatani, Yoichiro |
| dc.date.none.fl_str_mv | 2011 2016-03-17T11:51:20Z 2016-03-17T11:51:20Z 2016-03-17 |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10725/3353 http://dx.doi.org/10.1371/journal.pone.0029427 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. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029427 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | PLOS One |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_ac450d8636142be5f29fac5a388c8ecd |
| identifier_str_mv | 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. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/3353 |
| publishDate | 2011 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Large scale association analysis identifies three susceptibility loci for coronary artery diseaseEl-Khazen, GeorgesZalloua, Pierre A.Saade, StephanieCazier, Jean-BaptisteGhassibe-Sabbagh, MichellaYouhanna, SoniaBadro, Danielle A.Kamatani, YoichiroGenome 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.PublishedN/A2016-03-17T11:51:20Z2016-03-17T11:51:20Z20112016-03-17Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10725/3353http://dx.doi.org/10.1371/journal.pone.0029427Saade, 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.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029427enPLOS Oneinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/33532019-07-25T11:17:02Z |
| spellingShingle | Large scale association analysis identifies three susceptibility loci for coronary artery disease El-Khazen, Georges |
| status_str | publishedVersion |
| title | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| title_full | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| title_fullStr | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| title_full_unstemmed | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| title_short | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| title_sort | Large scale association analysis identifies three susceptibility loci for coronary artery disease |
| url | http://hdl.handle.net/10725/3353 http://dx.doi.org/10.1371/journal.pone.0029427 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029427 |