Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke
Publication year
2016Author(s)
Source
Neurology, 86, 2, (2016), pp. 146-53ISSN
Publication type
Article / Letter to editor

Display more detailsDisplay less details
Organization
Neurology
Journal title
Neurology
Volume
vol. 86
Issue
iss. 2
Page start
p. 146
Page end
p. 53
Subject
Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical NeuroscienceAbstract
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.
This item appears in the following Collection(s)
- Academic publications [227904]
- Electronic publications [107414]
- Faculty of Medical Sciences [86236]
- Open Access publications [76526]
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.