Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data
To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1 genes...
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Published in | Diabetes, obesity & metabolism Vol. 11; no. s1; pp. 60 - 66 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Oxford, UK : Blackwell Publishing Ltd
01.02.2009
Blackwell Publishing Ltd |
Subjects | |
Online Access | Get full text |
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Summary: | To develop novel methods for identifying new genes that contribute to the risk of developing type 1 diabetes within the Major Histocompatibility Complex (MHC) region on chromosome 6, independently of the known linkage disequilibrium (LD) between human leucocyte antigen (HLA)-DRB1, -DQA1, -DQB1 genes. We have developed a novel method that combines single nucleotide polymorphism (SNP) genotyping data with protein-protein interaction (ppi) networks to identify disease-associated network modules enriched for proteins encoded from the MHC region. Approximately 2500 SNPs located in the 4 Mb MHC region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein modules were statistically evaluated using permutation. A total of 151 genes could be mapped to nodes within the protein interaction network and their interaction partners were identified. Five protein interaction modules reached statistical significance using this approach. The identified proteins are well known in the pathogenesis of T1D, but the modules also contain additional candidates that have been implicated in β-cell development and diabetic complications. The extensive LD within the MHC region makes it important to develop new methods for analysing genotyping data for identification of additional risk genes for T1D. Combining genetic data with knowledge about functional pathways provides new insight into mechanisms underlying T1D. |
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Bibliography: | http://dx.doi.org/10.1111/j.1463-1326.2008.01004.x ark:/67375/WNG-JDZRV1M1-X istex:6F917E6C58FD2B291163247CD2CAE84130AF24BE ArticleID:DOM1004 Conflict of interest The authors declare that they have no conflicts of interest in publishing this article. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1462-8902 1463-1326 |
DOI: | 10.1111/j.1463-1326.2008.01004.x |