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Dichgans, M.* ; Malik, R.* ; König, I.R.* ; Rosand, J.* ; Clarke, R.* ; Gretarsdottir, S.* ; Thorleifsson, G.* ; Mitchell, B.D.* ; Assimes, T.L.* ; Levi, C.* ; O'Donnell, C.J.* ; Fornage, M.* ; Thorsteinsdottir, U.* ; Psaty, B.M.* ; Hengstenberg, C.* ; Seshadri, S* ; Erdmann, J.* ; Bis, J.C.* ; Peters, A. ; Boncoraglio, G.B.* ; Marz, W.* ; Meschia, J.F.* ; Kathiresan, S.* ; Ikram, M.A.* ; McPherson, R.* ; Stefansson, K.* ; Sudlow, C.* ; Reilly, M.P.* ; Thompson, J.R.* ; Sharma, P.* ; Hopewell, J.C.* ; Chambers, J.C.* ; Watkins, H.* ; Rothwell, P.M.* ; Roberts, R.* ; Markus, H.S.* ; Samani, N.J.* ; Farrall, M.* ; Schunkert, H.* ; METASTROKE Consortium (*) ; CARDIoGRAM Consortium (Döring, A. ; Wichmann, H.-E. ; Illig, T. ; Klopp, N. ; Meisinger, C. ; Peters, A. ; Meitinger, T.) ; C4D Consortium (*) ; International Stroke Genetics Consortium (*)

Shared genetic susceptibility to ischemic stroke and coronary artery disease: A genome-wide analysis of common variants.

Stroke 45, 24-36 (2014)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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<5×10-8) 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 (PIS=1.62×10-7) and ABO (PIS=2.6×10-4), as well as at HDAC9 (PLAS=2.32×10-12), 9p21 (PLAS=3.70×10-6), RAI1-PEMT-RASD1 (PLAS=2.69×10-5), EDNRA (PLAS=7.29×10-4), and CYP17A1-CNNM2-NT5C2 (PLAS=4.9×10-4). CONCLUSIONS: Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.  
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Coronary Artery Disease ; Genetics ; Meta-analysis ; Polymorphism ; Single Nucleotide ; Stroke; Association Metaanalysis; Atherosclerotic Stroke; Risk-factors; Loci; Mortality; Pressure; Design
ISSN (print) / ISBN 0039-2499
e-ISSN 1524-4628
Zeitschrift Stroke
Quellenangaben Band: 45, Heft: 1, Seiten: 24-36 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed