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    The Missing Heritability in T1D and Potential New Targets for Prevention

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    Authors
    Pierce, Brian G.
    Eberwine, Ryan
    Noble, Janelle A.
    Habib, Michael
    Shulha, Hennady P.
    Weng, Zhiping
    Blankenhorn, Elizabeth P.
    Mordes, John P.
    UMass Chan Affiliations
    Department of Medicine, Division of Endocrinology and Metabolism
    Program in Bioinformatics and Integrative Biology
    Document Type
    Journal Article
    Publication Date
    2013-02-13
    Keywords
    Bioinformatics
    Endocrinology, Diabetes, and Metabolism
    Immunoprophylaxis and Therapy
    
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    Abstract
    Type 1 diabetes (T1D) is a T cell-mediated disease. It is strongly associated with susceptibility haplotypes within the major histocompatibility complex, but this association accounts for an estimated 50% of susceptibility. Other studies have identified as many as 50 additional susceptibility loci, but the effect of most is very modest (odds ratio (OR) 5) and that deletion of V beta 13+ T cells prevents diabetes. A role for the TCR is also suspected in NOD mice, but TCR regions have not been associated with human T1D. To investigate this disparity, we tested the hypothesis in silico that previous studies of human T1D genetics were underpowered to detect MHC-contingent TCR susceptibility. We show that stratifying by MHC markedly increases statistical power to detect potential TCR susceptibility alleles. We suggest that the TCR regions are viable candidates for T1D susceptibility genes, could account for "missing heritability," and could be targets for prevention.
    Source
    Brian G. Pierce, Ryan Eberwine, Janelle A. Noble, et al., “The Missing Heritability in T1D and Potential New Targets for Prevention,” Journal of Diabetes Research, vol. 2013, Article ID 737485, 10 pages, 2013. doi:10.1155/2013/737485. Link to article on publisher's site
    DOI
    10.1155/2013/737485
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/29991
    PubMed ID
    23691517
    Related Resources
    Link to Article in PubMed
    Rights
    Copyright 2013 Brian G. Pierce et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    ae974a485f413a2113503eed53cd6c53
    10.1155/2013/737485
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    UMass Chan Faculty and Researcher Publications
    Program in Bioinformatics and Integrative Biology Publications

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