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Genetic Drivers of von Willebrand Factor Levels in an Ischemic Stroke Population and Association With Risk for Recurrent Stroke
- Source :
- Stroke. 48:1444-1450
- Publication Year :
- 2017
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2017.
-
Abstract
- Background and Purpose— von Willebrand factor (vWF) plays an important role in thrombus formation during cerebrovascular damage. We sought to investigate the potential role of circulating vWF in recurrent cerebrovascular events and identify genetic contributors to variation in vWF level in an ischemic stroke population. Methods— We analyzed the effect of circulating vWF on risk of recurrent stroke using survival models in the VISP trial (Vitamin Intervention for Stroke Prevention) and the use of vWF in reclassification over traditional factors. We conducted a genome-wide association study) with imputation, based on 1000 Genomes Project data, for circulating vWF levels and then interrogated loci previously associated with vWF levels. We performed expression quantitative trait locus analysis for vWF across different tissues. Results— Elevated vWF levels were associated with increased risk for recurrent stroke in VISP. Adding vWF to traditional clinical parameters also improved recurrent stroke risk prediction. We identified single-nucleotide polymorphisms significantly associated with circulating vWF at the ABO locus ( P −8 ) and replicated findings from previous genetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated ABO single-nucleotide polymorphisms were also associated with vWF gene expression. Conclusions— Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact vWF gene expression were identified. These data add to our knowledge of the pathophysiologic and genetic basis for recurrent stroke risk and may have implications for clinical care decision making.
- Subjects :
- Male
Risk
0301 basic medicine
congenital, hereditary, and neonatal diseases and abnormalities
medicine.medical_specialty
Quantitative Trait Loci
Population
Gene Expression
Genome-wide association study
Polymorphism, Single Nucleotide
Article
Brain Ischemia
Brain ischemia
03 medical and health sciences
0302 clinical medicine
Von Willebrand factor
Recurrence
Recurrent stroke
hemic and lymphatic diseases
Internal medicine
von Willebrand Factor
Humans
Medicine
Thrombus
education
Aged
Aged, 80 and over
Advanced and Specialized Nursing
education.field_of_study
biology
business.industry
Middle Aged
medicine.disease
Surgery
Stroke
030104 developmental biology
Ischemic stroke
biology.protein
Cardiology
Female
Neurology (clinical)
Cardiology and Cardiovascular Medicine
business
030217 neurology & neurosurgery
Genome-Wide Association Study
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 15244628 and 00392499
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Stroke
- Accession number :
- edsair.doi.dedup.....a3236e699a3b194800351656dad386ee