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

Adib-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, YC; Mosley, T; Falcone, GJ; Furie, KL; Leiva-Salinas, C; Lau, BC; Khan, MS; Sharma, P; Fornage, M; Mitchell, BD; Psaty, BM; Sudlow, C; Levi, C; Boncoraglio, GB; Rothwell, PM; Meschia, J; Dichgans, M; Rosand, J; Markus, HS

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

Adib-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, YC Mosley, T Falcone, GJ Furie, KL Leiva-Salinas, C Lau, BC Khan, MS Sharma, P Fornage, M Mitchell, BD Psaty, BM Sudlow, C Levi, C Boncoraglio, GB Rothwell, PM Meschia, J Dichgans, M Rosand, J Markus, HS

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Publication Type:: Journal Article
Citation:: Stroke, 2013, 44 (6), pp. 1609 - 1615
Issue Date:: 2013-06-01

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Field	Value	Language
dc.contributor.author	Adib-Samii, P	en_US
dc.contributor.author	Rost, N	en_US
dc.contributor.author	Traylor, M	en_US
dc.contributor.author	Devan, W	en_US
dc.contributor.author	Biffi, A	en_US
dc.contributor.author	Lanfranconi, S	en_US
dc.contributor.author	Fitzpatrick, K	en_US
dc.contributor.author	Bevan, S	en_US
dc.contributor.author	Kanakis, A	en_US
dc.contributor.author	Valant, V	en_US
dc.contributor.author	Gschwendtner, A	en_US
dc.contributor.author	Malik, R	en_US
dc.contributor.author	Richie, A	en_US
dc.contributor.author	Gamble, D	en_US
dc.contributor.author	Segal, H	en_US
dc.contributor.author	Parati, EA	en_US
dc.contributor.author	Ciusani, E	en_US
dc.contributor.author	Holliday, EG	en_US
dc.contributor.author	Maguire, J https://orcid.org/0000-0001-5722-8311	en_US
dc.contributor.author	Wardlaw, J	en_US
dc.contributor.author	Worrall, B	en_US
dc.contributor.author	Bis, J	en_US
dc.contributor.author	Wiggins, KL	en_US
dc.contributor.author	Longstreth, W	en_US
dc.contributor.author	Kittner, SJ	en_US
dc.contributor.author	Cheng, YC	en_US
dc.contributor.author	Mosley, T	en_US
dc.contributor.author	Falcone, GJ	en_US
dc.contributor.author	Furie, KL	en_US
dc.contributor.author	Leiva-Salinas, C	en_US
dc.contributor.author	Lau, BC	en_US
dc.contributor.author	Khan, MS	en_US
dc.contributor.author	Sharma, P	en_US
dc.contributor.author	Fornage, M	en_US
dc.contributor.author	Mitchell, BD	en_US
dc.contributor.author	Psaty, BM	en_US
dc.contributor.author	Sudlow, C	en_US
dc.contributor.author	Levi, C	en_US
dc.contributor.author	Boncoraglio, GB	en_US
dc.contributor.author	Rothwell, PM	en_US
dc.contributor.author	Meschia, J	en_US
dc.contributor.author	Dichgans, M	en_US
dc.contributor.author	Rosand, J	en_US
dc.contributor.author	Markus, HS	en_US
dc.date.issued	2013-06-01	en_US
dc.identifier.citation	Stroke, 2013, 44 (6), pp. 1609 - 1615	en_US
dc.identifier.issn	0039-2499	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116337
dc.description.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 singlenucleotide 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. © 2013 American Heart Association, Inc.	en_US
dc.relation.ispartof	Stroke	en_US
dc.relation.isbasedon	10.1161/STROKEAHA.113.679936	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Brain	en_US
dc.subject.mesh	Nerve Fibers, Myelinated	en_US
dc.subject.mesh	Chromosomes, Human, Pair 17	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Magnetic Resonance Imaging	en_US
dc.subject.mesh	Linear Models	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Genotype	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Stroke	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.subject.mesh	Stroke, Lacunar	en_US
dc.title	17q25 locus is associated with white matter hyperintensity volume in ischemic stroke, but not with lacunar stroke status	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	44	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	44	en_US

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 singlenucleotide 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. © 2013 American Heart Association, Inc.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/116337