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|a dc
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|a Patsopoulos, Nikolaos A.
|e author
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|a Harvard University-
|e contributor
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|a Hafler, David A.
|e contributor
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|a Barcellos, Lisa F.
|e author
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|a Hintzen, Rogier Q.
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|a Schaefer, Catherine
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|a van Duijn, Cornelia M.
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|a Noble, Janelle A.
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|a Raj, Towfique
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|a Gourraud, Pierre-Antoine
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|a Stranger, Barbara E.
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|a Oksenberg, Jorge
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|a Olsson, Tomas
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|a Taylor, Bruce V.
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|a Sawcer, Stephen
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|a Hafler, David A.
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|a Carrington, Mary
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|a De Jager, Philip L.
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|a de Bakker, Paul I. W.
|e author
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|a Fine-Mapping the Genetic Association of the Major Histocompatibility Complex in Multiple Sclerosis: HLA and Non-HLA Effects
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|b Public Library of Science,
|c 2013-12-30T20:34:50Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/83401
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|a The major histocompatibility complex (MHC) region is strongly associated with multiple sclerosis (MS) susceptibility. HLA-DRB1*15:01 has the strongest effect, and several other alleles have been reported at different levels of validation. Using SNP data from genome-wide studies, we imputed and tested classical alleles and amino acid polymorphisms in 8 classical human leukocyte antigen (HLA) genes in 5,091 cases and 9,595 controls. We identified 11 statistically independent effects overall: 6 HLA-DRB1 and one DPB1 alleles in class II, one HLA-A and two B alleles in class I, and one signal in a region spanning from MICB to LST1. This genomic segment does not contain any HLA class I or II genes and provides robust evidence for the involvement of a non-HLA risk allele within the MHC. Interestingly, this region contains the TNF gene, the cognate ligand of the well-validated TNFRSF1A MS susceptibility gene. The classical HLA effects can be explained to some extent by polymorphic amino acid positions in the peptide-binding grooves. This study dissects the independent effects in the MHC, a critical region for MS susceptibility that harbors multiple risk alleles.
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|a R01NS049477
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|a R01NS026799
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|a NIH/NINDS R01NS049510
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|a R01NS0495103
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|a NIH/NIAID R01AI076544
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|a en_US
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|a Article
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|t PLoS Genetics
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