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17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.

Title17q25 Locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status.
Publication TypeJournal Article
Year of Publication2013
AuthorsAdib-Samii P, Rost N, Traylor M, Devan W, Biffi A, Lanfranconi S, Fitzpatrick K, Bevan S, Kanakis A, Valant V, Gschwendtner A, Malik R, Richie A, Gamble D, Segal H, Parati EA, Ciusani E, Holliday EG, Maguire J, Wardlaw J, Worrall B, Bis J, Wiggins KL, Longstreth W, Kittner SJ, Cheng Y-C, Mosley T, Falcone GJ, Furie KL, Leiva-Salinas C, Lau BC, Khan MSaleem, Sharma P, Fornage M, Mitchell BD, Psaty BM, Sudlow C, Levi C, Boncoraglio GB, Rothwell PM, Meschia J, Dichgans M, Rosand J, Markus HS
Corporate AuthorsAustralian Stroke Genetics Collaborative, Wellcome Trust Case-Control Consortium-2(WTCCC2), METASTROKE, International Stroke Genetics Consortium
Date Published2013 Jun
KeywordsAdult, Aged, Aged, 80 and over, Brain, Case-Control Studies, Chromosomes, Human, Pair 17, Female, Genome-Wide Association Study, Genotype, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Fibers, Myelinated, Polymorphism, Single Nucleotide, Stroke, Stroke, Lacunar

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.

Alternate JournalStroke
PubMed ID23674528
PubMed Central IDPMC3771337
Grant ListK23 NS064052 / NS / NINDS NIH HHS / United States
095626 / / Wellcome Trust / United Kingdom
P30 DK072488 / DK / NIDDK NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
/ / Wellcome Trust / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
K23NS064052 / NS / NINDS NIH HHS / United States
G0900295 / / Medical Research Council / United Kingdom
/ ImNIH / Intramural NIH HHS / United States