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

Research output: Contribution to journalArticle

Matthew Traylor, Cathy R. Zhang, Poneh Adib-Samii, William J. Devan, Owen E. Parsons, Silvia Lanfranconi, Sarah Gregory, Lisa Cloonan, Guido J. Falcone, Farid Radmanesh, Kaitlin Fitzpatrick, Allison Kanakis, Thomas R. Barrick, Barry Moynihan, Cathryn M. Lewis, Giorgio B. Boncoraglio, Robin Lemmens, Vincent Thijs, Cathie Sudlow, Joanna Wardlaw & 10 others Peter M. Rothwell, James F. Meschia, Bradford B. Worrall, Christopher Levi, Steve Bevan, Karen L. Furie, Martin Dichgans, Jonathan Rosand, Hugh S. Markus, Natalia Rost

Original languageEnglish
Pages (from-to)146-153
Number of pages8
JournalNeurology
Volume86
Issue number2
DOIs
StatePublished - 12 Jan 2016

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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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