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    HERITABILITY AND SEX-EFFECT ANALYSES OF NEURODEGENERATIVE DISEASE

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    TETDEDXKeller-temple-0225E-119 ...
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    Genre
    Thesis/Dissertation
    Date
    2014
    Author
    Keller, Margaux Finn
    Advisor
    Weitz, Charles A.
    Committee member
    Rockwell, Christie
    Nalls, Mike A.
    Kulathinal, Rob J.
    Schurr, Theodore G. (Theodore George), 1961-
    Department
    Anthropology
    Subject
    Genetics
    Neurosciences
    Gcta
    Gwas
    Heritability
    Populations
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/3096
    
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    DOI
    http://dx.doi.org/10.34944/dspace/3078
    Abstract
    This work analyzes the genetic basis of three neurodegenerative diseases using several thousands of individuals of European descent to determine a range of phenotypic heritability outside of what has been identified by prior methods. By measuring additive genetic variance genome-wide, measures of its contribution to the phenotypic variance of these diseases were substantially increased, in some instances by a factor of 10 or more. Additionally, regional-mapping methods identified segments of the genome exhibiting significantly high heritability estimates associated with one of the neurodegenerative diseases, Amyotrophic lateral sclerosis. This resulted in the detection of novel candidate regions and provided conclusive evidence for the polygenic architecture of this disease. Lastly, novel risk variants associated with Parkinson's disease were identified on the X chromosome, a previously ignored genomic region. Overall, the employment of new analytic methods produced robust and novel results, adding substantial information to the neurodegenerative disease literature and connecting the anthropological perspective with growing informatics-based methods.
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