Defining the role of the MHC in autoimmunity: a review and pooled analysis.

The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of the...

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Main Authors: Michelle M A Fernando, Christine R Stevens, Emily C Walsh, Philip L De Jager, Philippe Goyette, Robert M Plenge, Timothy J Vyse, John D Rioux
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-04-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000024&type=printable
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author Michelle M A Fernando
Christine R Stevens
Emily C Walsh
Philip L De Jager
Philippe Goyette
Robert M Plenge
Timothy J Vyse
John D Rioux
author_facet Michelle M A Fernando
Christine R Stevens
Emily C Walsh
Philip L De Jager
Philippe Goyette
Robert M Plenge
Timothy J Vyse
John D Rioux
author_sort Michelle M A Fernando
collection DOAJ
description The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits - multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) - in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity.
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spelling doaj-art-7ba9a0cf6da54566bc8498212da0a2ee2025-08-20T03:22:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-04-0144e100002410.1371/journal.pgen.1000024Defining the role of the MHC in autoimmunity: a review and pooled analysis.Michelle M A FernandoChristine R StevensEmily C WalshPhilip L De JagerPhilippe GoyetteRobert M PlengeTimothy J VyseJohn D RiouxThe major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits - multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) - in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000024&type=printable
spellingShingle Michelle M A Fernando
Christine R Stevens
Emily C Walsh
Philip L De Jager
Philippe Goyette
Robert M Plenge
Timothy J Vyse
John D Rioux
Defining the role of the MHC in autoimmunity: a review and pooled analysis.
PLoS Genetics
title Defining the role of the MHC in autoimmunity: a review and pooled analysis.
title_full Defining the role of the MHC in autoimmunity: a review and pooled analysis.
title_fullStr Defining the role of the MHC in autoimmunity: a review and pooled analysis.
title_full_unstemmed Defining the role of the MHC in autoimmunity: a review and pooled analysis.
title_short Defining the role of the MHC in autoimmunity: a review and pooled analysis.
title_sort defining the role of the mhc in autoimmunity a review and pooled analysis
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000024&type=printable
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