17q25 Locus Is Associated With White Matter Hyperintensity Volume in Ischemic Stroke, But Not With Lacunar Stroke Status
Year: 2013
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND PURPOSE: Recently, a novel locus at 17q25 was associated with white matter hyperintensities (WMH) on MRI in stroke-free individuals. We aimed to replicate the association with WMH volume (WMHV) in patients with ischemic stroke. If the association acts by promoting a small vessel arteriopathy, it might be expected to also associate with lacunar stroke. METHODS: We quantified WMH on MRI in the stroke-free hemisphere of 2588 ischemic stroke cases. Association between WMHV and 6 single-nucleotide polymorphisms at chromosome 17q25 was assessed by linear regression. These single-nucleotide polymorphisms were also investigated for association with lacunar stroke in 1854 cases and 51 939 stroke-free controls from METASTROKE. Meta-analyses with previous reports and a genetic risk score approach were applied to identify other novel WMHV risk variants and uncover shared genetic contributions to WMHV in community participants without stroke and ischemic stroke. RESULTS: Single-nucleotide polymorphisms at 17q25 were associated with WMHV in ischemic stroke, the most significant being rs9894383 (P=0.0006). In contrast, there was no association between any single-nucleotide polymorphism and lacunar stroke. A genetic risk score analysis revealed further genetic components to WMHV shared between community participants without stroke and ischemic stroke. CONCLUSIONS: This study provides support for an association between the 17q25 locus and WMH. In contrast, it is not associated with lacunar stroke, suggesting that the association does not act by promoting small-vessel arteriopathy or the same arteriopathy responsible for lacunar infarction.
Source: Stroke
Authors: Poneh Adib-Samii, Natalia Rost, Matthew Traylor, William Devan, Alessandro Biffi, Silvia Lanfranconi, Kaitlin Fitzpatrick, Steve Bevan, Allison Kanakis, Valerie Valant, Andreas Gschwendtner, Rainer Malik, Alexa Richie, Dale Gamble, Helen Segal, Eugenio A. Parati, Emilio Ciusani, Elizabeth G. Holliday, Jane Maguire, Joanna Wardlaw, Bradford Worrall, Joshua Bis, Kerri L. Wiggins, Will Longstreth, Steve J. Kittner, Yu-Ching Cheng, Thomas Mosley, Guido J. Falcone, Karen L. Furie, Carlos Leiva-Salinas, Benison C. Lau, Muhammed Saleem Khan, Australian Stroke Genetics Collaborative, METASTROKE, Pankaj Sharma, Myriam Fornage, Braxton D. Mitchell, Bruce M. Psaty, Cathie Sudlow, Christopher Levi, Giorgio B. Boncoraglio, Peter M. Rothwell, James Meschia, Martin Dichgans, Jonathan Rosand, Hugh S. Markus
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Improving prevention of stroke by better understanding of existing risk factors and treatments., CHARGE consortium: omics discovery for CVD and aging phenotypes, Genetic variation in white matter hyperintensity and risk of ischemic stroke, Mid-Atlantic Nutrition Obesity Research Center, Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics.
OpenAlex ID: W2016216374