Genetic Associations With White Matter Hyperintensities Confer Risk of Lacunar Stroke

Matthew Traylor, Loes C A Rutten-Jacobs, Vincent Thijs, Elizabeth G. Holliday, Chris Levi, Steve Bevan, Rainer Malik, Giorgio Boncoraglio, Cathie Sudlow, Peter M. Rothwell, Martin Dichgans, Hugh S. Markus

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Purpose - White matter hyperintensities (WMH) are increased in patients with lacunar stroke. Whether this is because of shared pathogenesis remains unknown. Using genetic data, we evaluated whether WMH-associated genetic susceptibility factors confer risk of lacunar stroke, and therefore whether they share pathogenesis. Methods - We used a genetic risk score approach to test whether single nucleotide polymorphisms associated with WMH in community populations were associated with magnetic resonance imaging-confirmed lacunar stroke (n=1,373), as well as cardioembolic (n=1,331) and large vessel (n=1,472) Trial of Org 10172 in Acute Stroke Treatment subtypes, against 9,053 controls. Second, we separated lacunar strokes into those with WMH (n=568) and those without (n=787) and tested for association with the risk score in these 2 groups. In addition, we evaluated whether WMH-associated single nucleotide polymorphisms are associated with lacunar stroke, or in the 2 groups. Results - The WMH genetic risk score was associated with lacunar stroke (odds ratio [OR; 95% confidence interval [CI]]=1.14 [1.06-1.22]; P=0.0003), in patients both with and without WMH (WMH: OR [95% CI]=1.15 [1.05-1.26]; P=0.003 and no WMH: OR [95% CI]=1.11 [1.02-1.21]; P=0.019). Conversely, the risk score was not associated with cardioembolic stroke (OR [95% CI]=1.03 [0.97-1.09]; P=0.63) or large vessel stroke (OR [95% CI]=0.99 [0.93,1.04]; P=0.39). However, none of the WMH-associated single nucleotide polymorphisms passed Bonferroni-corrected significance for association with lacunar stroke. Conclusions - Genetic variants that influence WMH are associated with an increased risk of lacunar stroke but not cardioembolic or large vessel stroke. Some genetic susceptibility factors seem to be shared across different radiological manifestations of small vessel disease.

Original languageEnglish
Pages (from-to)1174-1179
Number of pages6
JournalStroke
Volume47
Issue number5
DOIs
Publication statusPublished - May 1 2016

Keywords

  • cerebral small vessel diseases
  • genetic association studies
  • genetics
  • leukoencephalopathies
  • stroke, lacunar

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialised Nursing

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