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Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk
DC Field | Value | Language |
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dc.contributor.author | Hu, Xinli | - |
dc.contributor.author | Deutsch, Aaron J. | - |
dc.contributor.author | Lenz, Tobias L. | - |
dc.contributor.author | Onengut-Gumuscu, Suna | - |
dc.contributor.author | Han, Buhm | - |
dc.contributor.author | Chen, Wei-Min | - |
dc.contributor.author | Howson, Joanna M. M. | - |
dc.contributor.author | Todd, John A. | - |
dc.contributor.author | De Bakker, Paul I. W. | - |
dc.contributor.author | Rich, Stephen S. | - |
dc.contributor.author | Raychaudhuri, Soumya | - |
dc.date.accessioned | 2023-04-26T05:10:04Z | - |
dc.date.available | 2023-04-26T05:10:04Z | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.created | 2023-04-21 | - |
dc.date.issued | 2015-08 | - |
dc.identifier.citation | Nature Genetics, Vol.47 No.8, pp.898-905 | - |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | https://hdl.handle.net/10371/191590 | - |
dc.description.abstract | Variation in the human leukocyte antigen (HLA) genes accounts for one-half of the genetic risk in type 1 diabetes (T1D). Amino acid changes in the HLA-DR and HLA-DQ molecules mediate most of the risk, but extensive linkage disequilibrium complicates the localization of independent effects. Using 18,832 case-control samples, we localized the signal to 3 amino acid positions in HLA-DQ and HLA-DR. HLA-DQ. 1 position 57 (previously known; P = 1 x 10(-1,355)) by itself explained 15.2% of the total phenotypic variance. Independent effects at HLA-DR. 1 positions 13 (P = 1 x 10(-721)) and 71 (P = 1 x 10(-95)) increased the proportion of variance explained to 26.9%. The three positions together explained 90% of the phenotypic variance in the HLA-DRB1-HLA-DQA1-HLA-DQB1 locus. Additionally, we observed significant interactions for 11 of 21 pairs of common HLA-DRB1-HLA-DQA1-HLA-DQB1 haplotypes (P = 1.6 x 10(-64)). HLA-DR. 1 positions 13 and 71 implicate the P4 pocket in the antigen-binding groove, thus pointing to another critical protein structure for T1D risk, in addition to the HLA-DQ P9 pocket. | - |
dc.language | 영어 | - |
dc.publisher | Nature Publishing Group | - |
dc.title | Additive and interaction effects at three amino acid positions in HLA-DQ and HLA-DR molecules drive type 1 diabetes risk | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/ng.3353 | - |
dc.citation.journaltitle | Nature Genetics | - |
dc.identifier.wosid | 000358674100014 | - |
dc.identifier.scopusid | 2-s2.0-84938256620 | - |
dc.citation.endpage | 905 | - |
dc.citation.number | 8 | - |
dc.citation.startpage | 898 | - |
dc.citation.volume | 47 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Han, Buhm | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | SEROPOSITIVE RHEUMATOID-ARTHRITIS | - |
dc.subject.keywordPlus | CD8 T-CELLS | - |
dc.subject.keywordPlus | MHC | - |
dc.subject.keywordPlus | SUSCEPTIBILITY | - |
dc.subject.keywordPlus | MELLITUS | - |
dc.subject.keywordPlus | DECARBOXYLASE | - |
dc.subject.keywordPlus | ASSOCIATIONS | - |
dc.subject.keywordPlus | VARIANTS | - |
dc.subject.keywordPlus | GENOTYPE | - |
dc.subject.keywordPlus | DISEASE | - |
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