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The Missing Heritability in T1D and Potential New Targets for Prevention
Joint Authors
Pierce, Brian G.
Blankenhorn, Elizabeth P.
Weng, Zhiping
Eberwine, Ryan
Noble, Janelle A.
Habib, Michael
Mordes, John P.
Shulha, Hennady P.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-03-13
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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 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.
American Psychological Association (APA)
Pierce, Brian G.& Eberwine, Ryan& Noble, Janelle A.& Habib, Michael& Shulha, Hennady P.& Weng, Zhiping…[et al.]. 2013. The Missing Heritability in T1D and Potential New Targets for Prevention. Journal of Diabetes Research،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-494689
Modern Language Association (MLA)
Pierce, Brian G.…[et al.]. The Missing Heritability in T1D and Potential New Targets for Prevention. Journal of Diabetes Research No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-494689
American Medical Association (AMA)
Pierce, Brian G.& Eberwine, Ryan& Noble, Janelle A.& Habib, Michael& Shulha, Hennady P.& Weng, Zhiping…[et al.]. The Missing Heritability in T1D and Potential New Targets for Prevention. Journal of Diabetes Research. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-494689
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-494689