Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

Traylor, M; Zhang, CR; Adib-Samii, P; Devan, WJ; Parsons, OE; Lanfranconi, S; Gregory, S; Cloonan, L; Falcone, GJ; Radmanesh, F; Fitzpatrick, K; Kanakis, A; Barrick, TR; Moynihan, B; Lewis, CM; Boncoraglio, GB; Lemmens, R; Thijs, V; Sudlow, C; Wardlaw, J; Rothwell, PM; Meschia, JF; Worrall, BB; Levi, C; Bevan, S; Furie, KL; Dichgans, M; Rosand, J; Markus, HS; Rost, N; International Stroke Genetics Consortium,

Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.

Traylor, M Zhang, CR Adib-Samii, P Devan, WJ Parsons, OE Lanfranconi, S Gregory, S Cloonan, L Falcone, GJ Radmanesh, F Fitzpatrick, K Kanakis, A Barrick, TR Moynihan, B Lewis, CM Boncoraglio, GB Lemmens, R Thijs, V Sudlow, C Wardlaw, J Rothwell, PM Meschia, JF Worrall, BB Levi, C Bevan, S Furie, KL Dichgans, M Rosand, J Markus, HS Rost, N International Stroke Genetics Consortium,

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Publisher:: LIPPINCOTT WILLIAMS & WILKINS
Publication Type:: Journal Article
Citation:: Neurology, 2016, 86, (2), pp. 146-153
Issue Date:: 2016-01-12

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Field	Value	Language
dc.contributor.author	Traylor, M
dc.contributor.author	Zhang, CR
dc.contributor.author	Adib-Samii, P
dc.contributor.author	Devan, WJ
dc.contributor.author	Parsons, OE
dc.contributor.author	Lanfranconi, S
dc.contributor.author	Gregory, S
dc.contributor.author	Cloonan, L
dc.contributor.author	Falcone, GJ
dc.contributor.author	Radmanesh, F
dc.contributor.author	Fitzpatrick, K
dc.contributor.author	Kanakis, A
dc.contributor.author	Barrick, TR
dc.contributor.author	Moynihan, B
dc.contributor.author	Lewis, CM
dc.contributor.author	Boncoraglio, GB
dc.contributor.author	Lemmens, R
dc.contributor.author	Thijs, V
dc.contributor.author	Sudlow, C
dc.contributor.author	Wardlaw, J
dc.contributor.author	Rothwell, PM
dc.contributor.author	Meschia, JF
dc.contributor.author	Worrall, BB
dc.contributor.author	Levi, C
dc.contributor.author	Bevan, S
dc.contributor.author	Furie, KL
dc.contributor.author	Dichgans, M
dc.contributor.author	Rosand, J
dc.contributor.author	Markus, HS
dc.contributor.author	Rost, N
dc.contributor.author	International Stroke Genetics Consortium,
dc.date.accessioned	2022-04-25T23:56:33Z
dc.date.available	2015-09-09
dc.date.available	2022-04-25T23:56:33Z
dc.date.issued	2016-01-12
dc.identifier.citation	Neurology, 2016, 86, (2), pp. 146-153
dc.identifier.issn	0028-3878
dc.identifier.issn	1526-632X
dc.identifier.uri	http://hdl.handle.net/10453/156589
dc.description.abstract	OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	LIPPINCOTT WILLIAMS & WILKINS
dc.relation.ispartof	Neurology
dc.relation.isbasedon	10.1212/WNL.0000000000002263
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
dc.subject.classification	Neurology & Neurosurgery
dc.subject.mesh	Cerebral Small Vessel Diseases
dc.subject.mesh	Genetic Predisposition to Disease
dc.subject.mesh	Genetic Testing
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Humans
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Risk Factors
dc.subject.mesh	Stroke
dc.subject.mesh	White Matter
dc.subject.mesh	Humans
dc.subject.mesh	Genetic Predisposition to Disease
dc.subject.mesh	Risk Factors
dc.subject.mesh	Polymorphism, Single Nucleotide
dc.subject.mesh	Stroke
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Genetic Testing
dc.subject.mesh	Cerebral Small Vessel Diseases
dc.subject.mesh	White Matter
dc.title	Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke.
dc.type	Journal Article
utslib.citation.volume	86
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1109 Neurosciences
utslib.for	1702 Cognitive Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-25T23:56:31Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	86
utslib.citation.issue	2

Abstract:

OBJECTIVE: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. METHODS: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. RESULTS: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10(-6)) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10(-8); rs941898 [EVL], p = 4.0 × 10(-8); rs962888 [C1QL1], p = 1.1 × 10(-8); rs9515201 [COL4A2], p = 6.9 × 10(-9)). CONCLUSIONS: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease.

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http://hdl.handle.net/10453/156589