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

Traylor, Matthew and Zhang, Cathy R. and Adib-Samii, Poneh and Devan, William J. and Parsons, Owen E. and Lanfranconi, Silvia and Gregory, Sarah and Cloonan, Lisa and Falcone, Guido J. and Radmanesh, Farid and Fitzpatrick, Kaitlin and Kanakis, Allison and Barrick, Thomas R. and Moynihan, Barry and Lewis, Cathryn M. and Boncoraglio, Giorgio B. and Lemmens, Robin and Thijs, Vincent and Sudlow, Cathie and Wardlaw, Joanna and Rothwell, Peter M. and Meschia, James F. and Worrall, Bradford B. and Levi, Christopher and Bevan, Steve and Furie, Karen L. and Dichgans, Martin and Rosand, Jonathan and Markus, Hugh S. and Rost, Natalia (2016) Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke. Neurology, 86 (2). pp. 146-153. ISSN 0028-3878

Full content URL: http://dx.doi.org/10.1212/WNL.0000000000002263

Documents
23607 Neurology-2016-Traylor-146-53.pdf
[img]
[Download]
[img]
Preview
PDF
23607 Neurology-2016-Traylor-146-53.pdf - Whole Document

337kB
Item Type:Article
Item Status:Live Archive

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.

Keywords:Stroke Genetics, NotOAChecked, JCOpen
Subjects:C Biological Sciences > C400 Genetics
Divisions:College of Science > School of Life Sciences
ID Code:23607
Deposited On:28 Jul 2016 19:03

Repository Staff Only: item control page