Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 배상철 | - |
dc.date.accessioned | 2018-02-08T06:15:54Z | - |
dc.date.available | 2018-02-08T06:15:54Z | - |
dc.date.issued | 2012-01 | - |
dc.identifier.citation | NATURE GENETICS, 권: 44, 호: 3, 페이지: 291-U91 | en_US |
dc.identifier.issn | 1061-4036 | - |
dc.identifier.uri | https://www.nature.com/articles/ng.1076 | - |
dc.description.abstract | The genetic association of the major histocompatibility complex (MHC) to rheumatoid arthritis risk has commonly been attributed to alleles in HLA-DRB1. However, debate persists about the identity of the causal variants in HLA-DRB1 and the presence of independent effects elsewhere in the MHC. Using existing genome-wide SNP data in 5,018 individuals with seropositive rheumatoid arthritis (cases) and 14,974 unaffected controls, we imputed and tested classical alleles and amino acid polymorphisms in HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1 and HLA-DRB1, as well as 3,117 SNPs across the MHC. Conditional and haplotype analyses identified that three amino acid positions (11, 71 and 74) in HLA-DR beta 1 and single-amino-acid polymorphisms in HLA-B (at position 9) and HLA-DP beta 1 (at position 9), which are all located in peptide-binding grooves, almost completely explain the MHC association to rheumatoid arthritis risk. This study shows how imputation of functional variation from large reference panels can help fine map association signals in the MHC. | en_US |
dc.description.sponsorship | We thank the Type 1 Diabetes Genetics Consortium and the Wellcome Trust Case Control Consortium for data access. We acknowledge use of the HLA genotyping data performed by the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory on the British 1958 Birth Cohort DNA collection. This project is supported by grants from the US National Institutes of Health (K08AR055688 (S. R.), R01-AR44422 (P. K. G.), R01-AR057108 and U01-GM092691 (R. M. P.)), the Korea Healthcare Technology Research and Development Project (A102065 and A111218-11-GM01 (H.-S. L. and S.-C. B.)), the Burroughs Wellcome Fund (R. M. P.), the Arthritis Foundation (S. R.) and by the Eileen Ludwig Greenland Center for Rheumatoid Arthritis (P.K.G.). | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA | en_US |
dc.title | Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis | en_US |
dc.type | Article | en_US |
dc.relation.no | 3 | - |
dc.relation.volume | 44 | - |
dc.identifier.doi | 10.1038/ng.1076 | - |
dc.relation.page | 291-91 | - |
dc.relation.journal | NATURE GENETICS | - |
dc.contributor.googleauthor | Raychaudhuri, Soumya | - |
dc.contributor.googleauthor | Sandor, Cynthia | - |
dc.contributor.googleauthor | Stahl, Eli A | - |
dc.contributor.googleauthor | Freudenberg, Jan | - |
dc.contributor.googleauthor | Lee, Hye-Soon | - |
dc.contributor.googleauthor | Jia, Xiaoming | - |
dc.contributor.googleauthor | Alfredsson, Lars | - |
dc.contributor.googleauthor | Padyukov, Leonid | - |
dc.contributor.googleauthor | Klareskog, Lars | - |
dc.contributor.googleauthor | Worthington, Jane | - |
dc.relation.code | 2012206936 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | scbae | - |
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