Program in Bioinformatics and Integrative Biology; Department of Medicine, Division of Endocrinology and Metabolism
Bioinformatics | Endocrinology, Diabetes, and Metabolism | Immunoprophylaxis and Therapy
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.
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Citation: 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
Pierce, Brian G.; Eberwine, Ryan; Noble, Janelle A.; Habib, Michael; Shulha, Hennady P.; Weng, Zhiping; Blankenhorn, Elizabeth P.; and Mordes, John P., "The Missing Heritability in T1D and Potential New Targets for Prevention" (2013). University of Massachusetts Medical School Faculty Publications. 221.