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Title: Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke.
Austin Authors: Traylor, Matthew;Rutten-Jacobs, Loes C A;Thijs, Vincent N ;Holliday, Elizabeth G;Levi, Chris;Bevan, Steve;Malik, Rainer;Boncoraglio, Giorgio;Sudlow, Cathie;Rothwell, Peter M;Dichgans, Martin;Markus, Hugh S
Affiliation: Division of Clinical Neurosciences, Neuroimaging Sciences and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom
Department of Medical and Molecular Genetics, King's College London, London, United Kingdom
Laboratory of Neurobiology, Vesalius Research Center, VIB, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease, University of Leuven, Leuven, Belgium
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
School of Medicine and Public Health and Centre for Clinical Epidemiology and Biostatistics, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia
School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
Department of Neurology, Austin Health, Heidelberg, Victoria, Australia
Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
School of Life Science, University of Lincoln, Lincoln, United Kingdom
Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-University, Munich, Germany
Department of Cerebrovascular Disease, IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
Stroke Prevention Research Unit, Nuffield Department of Neuroscience, University of Oxford, Oxford, United Kingdom
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
Issue Date: 2016
Date: 2016
Publication information: Stroke 2016; 47(5): 1174-9
Abstract: White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis. We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging-confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups. The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI]]=1.14 [1.06-1.22]; P=0.0003), in patients both with and without WMH (WMH: OR [95% CI]=1.15 [1.05-1.26]; P=0.003 and no WMH: OR [95% CI]=1.11 [1.02-1.21]; P=0.019). Conversely, the risk score was not associated with cardioembolic stroke (OR [95% CI]=1.03 [0.97-1.09]; P=0.63) or large vessel stroke (OR [95% CI]=0.99 [0.93,1.04]; P=0.39). However, none of the WMH-associated single nucleotide polymorphisms passed Bonferroni-corrected significance for association with lacunar stroke. Genetic variants that influence WMH are associated with an increased risk of lacunar stroke but not cardioembolic or large vessel stroke. Some genetic susceptibility factors seem to be shared across different radiological manifestations of small vessel disease.
DOI: 10.1161/STROKEAHA.115.011625
ORCID: 0000-0002-6614-8417
Journal: Stroke
PubMed URL: 27073246
Type: Journal Article
Subjects: cerebral small vessel diseases
genetic association studies
Stroke, lacunar
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