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From the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC (F.C.H.); Department of Public Health Sciences (W.M.C., A.M.S., S.S.R., B.B.W., M.M.S.), Department of Neurology (S.R.W., A.M.S., B.B.W.), and Center for Public Health Genomics (W.M.C., S.S.R., B.B.W., M.M.S.), University of Virginia, Charlottesville; Department of Biology (K.L.K.) and Center for Health Disparities (K.L.K.), East Carolina University, Greenville, NC; Department of Clinical Laboratory Sciences, University of Cape Town, South Africa (G.D.); Division of Nutritional Sciences, University of Illinois at Urbana-Champaign (J.L.R.); and Rhode Island Hospital and the Alpert Medical School, Brown University, Providence (K.L.F.).
Published: June 2017
AI Article Synopsis
Article 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 locus (<5×10) and replicated findings from previous genetic associations of vWF levels in humans. Expression quantitative trait locus analyses demonstrate that most associated single-nucleotide polymorphisms were also associated with gene expression.
Conclusions: Elevated vWF levels are associated with recurrent stroke in VISP. In the VISP population, genetic determinants of vWF levels that impact 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.
