Subtype Specificity of Genetic Loci Associated With Stroke in 16 664 Cases and 32 792 Controls
Autor: | Carl D. Langefeld, Christopher D. Anderson, Braxton D. Mitchell, Jordi Jimenez-Conde, Reinhold Schmidt, John W. Cole, Jonathan Rosand, Mary E. Comeau, Loes Rutten-Jacobs, Cathie Sudlow, Ralph L. Sacco, Raji P. Grewal, Hakan Ay, Matthew Traylor, Marta Ribasés, Tatjana Rundek, Daniel Woo, Hugh S. Markus, Rainer Malik, Kathryn M. Rexrode, Guido J. Falcone, Huichun Xu, Jin Moo Lee, Martin Dichgans, Steven J. Kittner |
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Přispěvatelé: | Traylor, Matthew [0000-0001-6624-8621], Jacobs, Loes [0000-0003-3223-885X], Markus, Hugh [0000-0002-9794-5996], Apollo - University of Cambridge Repository |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Genotype Biology Chromosome Cerebral hemorrhage Article 03 medical and health sciences 0302 clinical medicine medicine Haplotype Dementia Humans ddc:610 cardiovascular diseases Stroke Genetic association Aged Genetics Aged 80 and over Bayes Theorem General Medicine Middle Aged medicine.disease Atherosclerosis 3. Good health Europe 030104 developmental biology Genetic Loci Case-Control Studies genetics [Stroke] Female 030217 neurology & neurosurgery Genome-Wide Association Study |
Zdroj: | Circ Genom Precis Med Circulation 12(7), 2338 (2019). doi:10.1161/CIRCGEN.118.002338 Sudlow, C 2019, ' Subtype Specificity of Genetic Loci Associated With Stroke in 16 664 Cases and 32 792 Controls ', Circulation: Genomic and Precision Medicine, vol. 12, no. 7, e002338 . https://doi.org/10.1161/CIRCGEN.118.002338 Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
Popis: | Background: Genome-wide association studies have identified multiple loci associated with stroke. However, the specific stroke subtypes affected, and whether loci influence both ischemic and hemorrhagic stroke, remains unknown. For loci associated with stroke, we aimed to infer the combination of stroke subtypes likely to be affected, and in doing so assess the extent to which such loci have homogeneous effects across stroke subtypes. Methods: We performed Bayesian multinomial regression in 16 664 stroke cases and 32 792 controls of European ancestry to determine the most likely combination of stroke subtypes affected for loci with published genome-wide stroke associations, using model selection. Cases were subtyped under 2 commonly used stroke classification systems, TOAST (Trial of Org 10172 Acute Stroke Treatment) and causative classification of stroke. All individuals had genotypes imputed to the Haplotype Reference Consortium 1.1 Panel. Results: Sixteen loci were considered for analysis. Seven loci influenced both hemorrhagic and ischemic stroke, 3 of which influenced ischemic and hemorrhagic subtypes under both TOAST and causative classification of stroke. Under causative classification of stroke, 4 loci influenced both small vessel stroke and intracerebral hemorrhage. An EDNRA locus demonstrated opposing effects on ischemic and hemorrhagic stroke. No loci were predicted to influence all stroke subtypes in the same direction, and only one locus (12q24) was predicted to influence all ischemic stroke subtypes. Conclusions: Heterogeneity in the influence of stroke-associated loci on stroke subtypes is pervasive, reflecting differing causal pathways. However, overlap exists between hemorrhagic and ischemic stroke, which may reflect shared pathobiology predisposing to small vessel arteriopathy. Stroke is a complex, heterogeneous disorder requiring tailored analytic strategies to decipher genetic mechanisms. |
Databáze: | OpenAIRE |
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