Zhang, J. and Liang, F.M. and Dassen, W.R.M. and Doevendans, P.A. and de Gunst, M. (2003) Search for haplotype interactions that influence susceptibility to type 1 diabetes, through use of unphased genotype data. American Journal of Human Genetics, 73 (6). pp. 1385-1401. ISSN 0002-9297.
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Type 1 diabetes is a T-cell-mediated chronic disease characterized by the autoimmune destruction of pancreatic insulin-producing beta cells and complete insulin deficiency. It is the result of a complex interrelation of genetic and environmental factors, most of which have yet to be identified. Simultaneous identification of these genetic factors, through use of unphased genotype data, has received increasing attention in the past few years. Several approaches have been described, such as the modified transmission/disequilibrium test procedure, the conditional extended transmission/disequilibrium test, and the stepwise logistic-regression procedure. These approaches are limited either by being restricted to family data or by ignoring so-called "haplotype interactions" between alleles. To overcome this limit, the present study provides a general method to identify, on the basis of unphased genotype data, the haplotype blocks that interact to define the risk for a complex disease. The principle underpinning the proposal is minimal entropy. The performance of our procedure is illustrated for both simulated and real data. In particular, for a set of Dutch type 1 diabetes data, our procedure suggests some novel evidence of the interactions between and within haplotype blocks that are across chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 11, 12, 15, 16, 17, 19, and 21. The results demonstrate that, by considering interactions between potential disease haplotype blocks, we may succeed in identifying disease-predisposing genetic variants that might otherwise have remained undetected.
|Uncontrolled keywords:||DISEASE; LOCI; LINKAGE; COMPLEX; POLYMORPHISMS; EPISTASIS; PROMOTER; GENOME; IDDM1; HLA|
|Subjects:||H Social Sciences > HA Statistics|
|Divisions:||Faculties > Science Technology and Medical Studies > School of Mathematics Statistics and Actuarial Science|
|Depositing User:||Judith Broom|
|Date Deposited:||19 Dec 2007 18:22|
|Last Modified:||15 Oct 2012 13:08|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/596 (The current URI for this page, for reference purposes)|
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