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

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Title:	Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke
Author(s):	Traylor, M.; Zhang, C.R.; Adib-Samii, P.; Devan, W.J.; Parsons, O.E.; Lanfranconi, S.; Gregory, S.; Cloonan, L.; Falcone, G.J.; Radmanesh, F.; Fitzpatrick, K.; Kanakis, A.; Barrick, T.R.; Moynihan, B.; Lewis, C.M.; Boncoraglio, G.B.; Lemmens, R.; Thijs, V.; Sudlow, C.; Wardlaw, J.; Rothwell, P.M.; Meschia, J.F.; Worrall, B.B.; Levi, C.; Bevan, S.; Furie, K.L.; Dichgans, M.; Rosand, J.; Markus, H.S.; Rost, N.; Klijn, C.J.M. ; et al.
Publication year:	2016
Source:	Neurology, vol. 86, iss. 2, (2016), pp. 146-153
ISSN:	0028-3878
DOI:	https://doi.org/10.1212/WNL.0000000000002263
Publication type:	Article / Letter to editor
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/169551
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Subject:	Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience
Organization:	Neurology
Journal title:	Neurology
Volume:	vol. 86
Issue:	iss. 2
Page start:	p. 146
Page end:	p. 153
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 x 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 x 10(-8); rs941898 [EVL], p = 4.0 x 10(-8); rs962888 [C1QL1], p = 1.1 x 10(-8); rs9515201 [COL4A2], p = 6.9 x 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.