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    Genetic and Environmental Determinants of Quantitative Platelet Markers in the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study

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    Author
    Bozzi, Laura
    Advisor
    Yerges-Armstrong, Laura M.
    Date
    2014
    Type
    dissertation
    
    Metadata
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    Abstract
    Platelet size and count are associated with cardiac ischemia and ischemic stroke, two of the most common forms of acute cardiovascular disease. While platelet count (PC) is a common clinical measure, assessment of platelet size using mean platelet volume (MPV), the average size of platelets in a blood sample, and platelet distribution width (PDW), the variance of the platelet volume curve, are less frequently used. The overall objective of my research is to characterize these three quantitative platelet measures in a population of healthy individuals and evaluate the genetic and environmental determinants of these traits. While, MPV and PDW are not correlated (ρ<sub>p</sub>=0.07), PC is inversely correlated with both MPV (ρ<sub>p</sub>=-0.37) and PDW (ρ<sub>p</sub>=-0.27). Clinical and anthropometric predictors explain little of the variation in these three traits, however, all three are heritable, in particular MPV (h<super>2</super>: 0.83) and PC (h<super>2</super>: 0.67). A genome-wide association study (GWAS) was conducted for each of these three quantitative platelet traits. While no single nucleotide polymorphism (SNP) reached genome-wide significance (p<5x10-8) for any of the traits, 23 SNPs were associated at a suggestive level of significance (p<1x10-5) and some associated loci were near plausible candidate genes. We also queried well-established ischemic stroke and MI-associated SNPs for association with these platelet traits. We observed an MI-associated SNP near ANKSIA to be nominally associated with both MPV and PC (p=0.00795 and 0.00139, respectively). MPV, PC, and PDW are heritable traits and improved understanding of their genetic and environmental underpinnings could provide novel insight into platelet biology.
    Description
    University of Maryland, Baltimore. Epidemiology and Human Genetics. M.S. 2014
    Keyword
    platelet volume
    platelet distribution width
    Blood Platelets
    Cardiovascular Diseases--genetics
    Platelet Count
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/4046
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