Journal article
The Missing Heritability in T1D and Potential New Targets for Prevention
Journal of diabetes research, v 2013, pp 1-10
2013
PMID: 23691517
Featured in Collection : UN Sustainable Development Goals @ Drexel
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) <1.5). What accounts for the “missing heritability” is unknown and is often attributed to environmental factors. Here we review new data on the cognate ligand of MHC molecules, the T cell receptor (TCR). In rats, we found that one allele of a TCR variable gene, Vβ13A, is strongly associated with T1D (OR >5) and that deletion of Vβ13+ 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 hypothesisin silicothat 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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Details
- Title
- The Missing Heritability in T1D and Potential New Targets for Prevention
- Creators
- Brian G Pierce - Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USARyan Eberwine - Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA 19129, USAJanelle A Noble - Children’s Hospital Oakland Research Institute, Oakland, CA 94609, USAMichael Habib - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAHennady P Shulha - Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USAZhiping Weng - Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USAElizabeth P Blankenhorn - Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, PA 19129, USAJohn P Mordes - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA
- Publication Details
- Journal of diabetes research, v 2013, pp 1-10
- Publisher
- Wiley
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000318638500001
- Scopus ID
- 2-s2.0-84879354943
- Other Identifier
- 991014877656404721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Medicine, Research & Experimental