Dichgans, Martin and Malik, Rainer and Koenig, Inke R. and Rosand, Jonathan and Clarke, Robert and Gretarsdottir, Solveig and Thorleifsson, Gudmar and Mitchell, Braxton D. and Assimes, Themistocles L. and Levi, Christopher and O'Donnell, Christopher J. and Fornage, Myriam and Thorsteinsdottir, Unnur and Psaty, Bruce M. and Hengstenberg, Christian and Seshadri, Sudha and Erdmann, Jeanette and Bis, Joshua C. and Peters, Annette and Boncoraglio, Giorgio B. and Maerz, Winfried and Meschia, James F. and Kathiresan, Sekar and Ikram, M. Arfan and McPherson, Ruth and Stefansson, Kari and Sudlow, Cathie and Reilly, Muredach P. and Thompson, John R. and Sharma, Pankaj and Hopewell, Jemma C. and Chambers, John C. and Watkins, Hugh and Rothwell, Peter M. and Roberts, Robert and Markus, Hugh S. and Samani, Nilesh J. and Farrall, Martin and Schunkert, Heribert (2014) Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery Disease A Genome-Wide Analysis of Common Variants. STROKE, 45 (1). pp. 24-36. ISSN 0039-2499, 1524-4628
Full text not available from this repository. (Request a copy)Abstract
Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases. Methods Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype. Results Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5x10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (P-IS=1.62x10(-7)) and ABO (P-IS=2.6x10(-4)), as well as at HDAC9 (P-LAS=2.32x10(-12)), 9p21 (P-LAS=3.70x10(-6)), RAI1-PEMT-RASD1 (P-LAS=2.69x10(-5)), EDNRA (P-LAS=7.29x10(-4)), and CYP17A1-CNNM2-NT5C2 (P-LAS=4.9x10(-4)). Conclusions Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ASSOCIATION; METAANALYSIS; RISK; LOCI; PRESSURE; DESIGN; coronary artery disease; genetics; meta-analysis; polymorphism; single nucleotide; stroke |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Dec 2019 14:39 |
| Last Modified: | 02 Dec 2019 14:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/11113 |
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