Ischemic stroke is associated with the ABO locus: the EuroCLOT study
| العنوان: | Ischemic stroke is associated with the ABO locus: the EuroCLOT study |
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| المؤلفون: | Jonathan Rosand, Matthew Traylor, Sudha Seshadri, Veikko Salomaa, Robert Clarke, Anita L. DeStefano, Rodney J. Scott, Steve Bevan, Braxton D. Mitchell, Alun Evans, Philippe Amouyel, Myriam Fornage, Hugh S. Markus, Olli Saarela, Peter Wagner, Dylan Hodgkiss, Angela M. Carter, Giorgio B. Boncoraglio, Catherine Sudlow, K. L. Furie, Will Longstreth, Nicole Soranzo, Peter M. Rothwell, Jean Ferrières, John Attia, Bruce M. Psaty, Martin Dichgans, Christopher Levi, M. Arfan Ikram, Jarmo Virtamo, Gudmar Thorleifsson, Frances M K Williams, Pankaj Sharma, Martin Farrall, Kari Kuulasmaa, Per-Gunnar Wiklund, Elizabeth G. Holliday, James F. Meschia, Anna Helgadottir, Unnur Thorsteinsdottir, Michael A. Nalls, Peter J. Grant, Marco M Ferrario, Dominique Arveiler, Tim D. Spector, Andreas Gschwendtner, Eugenio Parati, Mari A. Kaunisto, Gabriela L. Surdulescu, Joshua C. Bis, Solveig Gretarsdottir, Kaisa Silander, Kari Stefansson, Thomas H. Mosely, Albert Hofman, Pirro G. Hysi, Yu-Ching Cheng, Aarno Palotie |
| المساهمون: | Radiology & Nuclear Medicine, Epidemiology |
| المصدر: | Annals of Neurology; Vol 73 Annals of Neurology Williams, F M K, Carter, A M, Hysi, P G, Surdulescu, G, Hodgkiss, D, Soranzo, N, Traylor, M, Bevan, S, Dichgans, M, Rothwell, P M W, Sudlow, C, Farrall, M, Silander, K, Kaunisto, M, Wagner, P, Saarela, O, Kuulasmaa, K, Virtamo, J, Salomaa, V, Amouyel, P, Arveiler, D, Ferrieres, J, Wiklund, P, Arfan Ikram, M, Hofman, A, Boncoraglio, G B, Parati, E A, Helgadottir, A, Gretarsdottir, S, Thorsteinsdottir, U, Thorleifsson, G, Stefansson, K, Seshadri, S, Destefano, A, Gschwendtner, A, Psaty, B, Longstreth, W, Mitchell, B D, Cheng, Y, Clarke, R, Ferrario, M, Bis, J C, Levi, C, Attia, J, Holliday, E G, Scott, R J, Fornage, M, Sharma, P, Furie, K L, Rosand, J, Nalls, M, Meschia, J, Mosely, T H, Evans, A, Palotie, A, Markus, H S, Grant, P J & Spector, T D 2013, ' Ischemic stroke is associated with the ABO locus: the EuroCLOT study. ', Annals of Neurology, vol. 73, no. 1, pp. 16-31 . https://doi.org/10.1002/ana.23838Test Annals of Neurology, 73(1), 16-31. John Wiley & Sons Inc. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Neurology, Genome-wide association study, 030204 cardiovascular system & hematology, Bioinformatics, Brain Ischemia, Brain ischemia, Coronary artery disease, Pathogenesis, Cohort Studies, 0302 clinical medicine, 80 and over, genetics, Genetics, Aged, 80 and over, biology, Atrial fibrillation, Single Nucleotide, Middle Aged, 3. Good health, Europe, Stroke, epidemiology, Female, Rapid Communication, Adult, medicine.medical_specialty, Adolescent, Polymorphism, Single Nucleotide, Fibrin, methods, ABO Blood-Group System, 03 medical and health sciences, Young Adult, ABO blood group system, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, Blood Coagulation, Aged, epidemiology/genetics, diagnosis/epidemiology/genetics, genetics, Adolescent, Adult, Aged, Aged, 80 and over, Blood Coagulation, genetics, Brain Ischemia, diagnosis/epidemiology/genetics, Cohort Studies, Europe, epidemiology, Female, Genetic Loci, genetics, Genetic Predisposition to Disease, epidemiology/genetics, Genetic Variation, genetics, Genome-Wide Association Study, methods, Humans, Male, Middle Aged, Polymorphism, genetics, Stroke, diagnosis/epidemiology/genetics, Young Adult, Genetic Variation, medicine.disease, Genetic Loci, biology.protein, Neurology (clinical), 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | OBJECTIVE: End-stage coagulation and the structure/function of fibrin are implicated in the pathogenesis of ischemic stroke. We explored whether genetic variants associated with end-stage coagulation in healthy volunteers account for the genetic predisposition to ischemic stroke and examined their influence on stroke subtype.METHODS: Common genetic variants identified through genome-wide association studies of coagulation factors and fibrin structure/function in healthy twins (n = 2,100, Stage 1) were examined in ischemic stroke (n = 4,200 cases) using 2 independent samples of European ancestry (Stage 2). A third clinical collection having stroke subtyping (total 8,900 cases, 55,000 controls) was used for replication (Stage 3).RESULTS: Stage 1 identified 524 single nucleotide polymorphisms (SNPs) from 23 linkage disequilibrium blocks having significant association (p < 5 × 10(-8)) with 1 or more coagulation/fibrin phenotypes. The most striking associations included SNP rs5985 with factor XIII activity (p = 2.6 × 10(-186)), rs10665 with FVII (p = 2.4 × 10(-47)), and rs505922 in the ABO gene with both von Willebrand factor (p = 4.7 × 10(-57)) and factor VIII (p = 1.2 × 10(-36)). In Stage 2, the 23 independent SNPs were examined in stroke cases/noncases using MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Wellcome Trust Case Control Consortium 2 collections. SNP rs505922 was nominally associated with ischemic stroke (odds ratio = 0.94, 95% confidence interval = 0.88-0.99, p = 0.023). Independent replication in Meta-Stroke confirmed the rs505922 association with stroke, beta (standard error, SE) = 0.066 (0.02), p = 0.001, a finding specific to large-vessel and cardioembolic stroke (p = 0.001 and p = < 0.001, respectively) but not seen with small-vessel stroke (p = 0.811). INTERPRETATION: ABO gene variants are associated with large-vessel and cardioembolic stroke but not small-vessel disease. This work sheds light on the different pathogenic mechanisms underpinning stroke subtype. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1531-8249 0364-5134 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6608414d9f9f00d9c383049e49fd4018Test http://ora.ox.ac.uk/objects/uuid:273d54ad-f9b4-4bdc-bca6-7667a92c622dTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6608414d9f9f00d9c383049e49fd4018 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15318249 03645134 |
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