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

Traylor, Matthew

Zhang, Cathy R

Adib-Samii, Poneh

Devan, William J

Parsons, Owen E

Lanfranconi, Silvia

Gregory, Sarah

Cloonan, Lisa

Falcone, Guido J

Radmanesh, Farid

Fitzpatrick, Kaitlin

Kanakis, Allison

Barrick, Thomas R

Moynihan, Barry

Lewis, Cathryn M

Boncoraglio, Giorgio B

Lemmens, Robin

Thijs, Vincent

Sudlow, Cathie

Wardlaw, Joanna

Rothwell, Peter M

Meschia, James F

Worrall, Bradford B

Levi, Christopher

Bevan, Steve

Furie, Karen L

Dichgans, Martin

Rosand, Jonathan

Markus, Hugh S

Rost, Natalia

International Stroke Genetics Consortium

United States

2017-05-01T17:18:43Z

2017-05-01T17:18:43Z

2016-01-12

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.

https://www.ncbi.nlm.nih.gov/pubmed/26674333

WNL.0000000000002263

1526-632X

https://hdl.handle.net/10161/14236

eng

Ovid Technologies (Wolters Kluwer Health)

Neurology

10.1212/WNL.0000000000002263

Cerebral Small Vessel Diseases

Genetic Predisposition to Disease

Genetic Testing

Genome-Wide Association Study

Humans

Polymorphism, Single Nucleotide

Risk Factors

Stroke

White Matter

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

Journal article

https://www.ncbi.nlm.nih.gov/pubmed/26674333

146

153

2

Anesthesiology

Anesthesiology, Neuroanesthesia

Clinical Science Departments

Duke

Neurology

Neurology, Neurocritical Care

School of Medicine

Published

86