Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
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König, Inke R
Mitchell, Braxton D
Assimes, Themistocles L
O'Donnell, Christopher J
Psaty, Bruce M
Bis, Joshua C
Boncoraglio, Giorgio B
Meschia, James F
Ikram, M Arfan
Reilly, Muredach P
Thompson, John R
Hopewell, Jemma C
Chambers, John C
Rothwell, Peter M
Markus, Hugh S
Samani, Nilesh J
MetadataShow full item record
CitationStroke 2014, 45 (1):24-36
AbstractIschemic 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.
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.
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)).
Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
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- Authors: Ding H, Xu Y, Wang X, Wang Q, Zhang L, Tu Y, Yan J, Wang W, Hui R, Wang CY, Wang DW
- Issue date: 2009 Aug
- Shared genetic basis for migraine and ischemic stroke: A genome-wide analysis of common variants.
- Authors: Malik R, Freilinger T, Winsvold BS, Anttila V, Vander Heiden J, Traylor M, de Vries B, Holliday EG, Terwindt GM, Sturm J, Bis JC, Hopewell JC, Ferrari MD, Rannikmae K, Wessman M, Kallela M, Kubisch C, Fornage M, Meschia JF, Lehtimäki T, Sudlow C, Clarke R, Chasman DI, Mitchell BD, Maguire J, Kaprio J, Farrall M, Raitakari OT, Kurth T, Ikram MA, Reiner AP, Longstreth WT Jr, Rothwell PM, Strachan DP, Sharma P, Seshadri S, Quaye L, Cherkas L, Schürks M, Rosand J, Ligthart L, Boncoraglio GB, Davey Smith G, van Duijn CM, Stefansson K, Worrall BB, Nyholt DR, Markus HS, van den Maagdenberg AM, Cotsapas C, Zwart JA, Palotie A, International Headache Genetics Consortium., Dichgans M, METASTROKE Collaboration of the International Stroke Genetics Consortium.
- Issue date: 2015 May 26
- Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies.
- Authors: Traylor M, Farrall M, Holliday EG, Sudlow C, Hopewell JC, Cheng YC, Fornage M, Ikram MA, Malik R, Bevan S, Thorsteinsdottir U, Nalls MA, Longstreth W, Wiggins KL, Yadav S, Parati EA, Destefano AL, Worrall BB, Kittner SJ, Khan MS, Reiner AP, Helgadottir A, Achterberg S, Fernandez-Cadenas I, Abboud S, Schmidt R, Walters M, Chen WM, Ringelstein EB, O'Donnell M, Ho WK, Pera J, Lemmens R, Norrving B, Higgins P, Benn M, Sale M, Kuhlenbäumer G, Doney AS, Vicente AM, Delavaran H, Algra A, Davies G, Oliveira SA, Palmer CN, Deary I, Schmidt H, Pandolfo M, Montaner J, Carty C, de Bakker PI, Kostulas K, Ferro JM, van Zuydam NR, Valdimarsson E, Nordestgaard BG, Lindgren A, Thijs V, Slowik A, Saleheen D, Paré G, Berger K, Thorleifsson G, Australian Stroke Genetics Collaborative, Wellcome Trust Case Control Consortium 2 (WTCCC2)., Hofman A, Mosley TH, Mitchell BD, Furie K, Clarke R, Levi C, Seshadri S, Gschwendtner A, Boncoraglio GB, Sharma P, Bis JC, Gretarsdottir S, Psaty BM, Rothwell PM, Rosand J, Meschia JF, Stefansson K, Dichgans M, Markus HS, International Stroke Genetics Consortium.
- Issue date: 2012 Nov
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