Association analysis of the extended MHC region in Celiac disease implicates multiple independent susceptibility loci

Richard Ahn, Yuan Chun Ding, Joseph A Murray, Alessio Fasano, Peter H R Green, Susan L. Neuhausen, Chad Garner

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Celiac disease is a common autoimmune disease caused by sensitivity to the dietary protein gluten. Forty loci have been implicated in the disease. All disease loci have been characterized as low-penetrance, with the exception of the high-risk genotypes in the HLA-DQA1 and HLA-DQB1 genes, which are necessary but not sufficient to cause the disease. The very strong effects from the known HLA loci and the genetically complex nature of the major histocompatibility complex (MHC) have precluded a thorough investigation of the region. The purpose of this study was to test the hypothesis that additional celiac disease loci exist within the extended MHC (xMHC). A set of 1898 SNPs was analyzed for association across the 7.6 Mb xMHC region in 1668 confirmed celiac disease cases and 517 unaffected controls. Conditional recursive partitioning was used to create an informative indicator of the known HLA-DQA1 and HLA-DQB1 high-risk genotypes that was included in the association analysis to account for their effects. A linkage disequilibrium-based grouping procedure was utilized to estimate the number of independent celiac disease loci present in the xMHC after accounting for the known effects. There was significant statistical evidence for four new independent celiac disease loci within the classic MHC region. This study is the first comprehensive association analysis of the xMHC in celiac disease that specifically accounts for the known HLA disease genotypes and the genetic complexity of the region.

Original languageEnglish (US)
Article numbere36926
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 17 2012

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celiac disease
major histocompatibility complex
Celiac Disease
Major Histocompatibility Complex
loci
Genotype
genotype
penetrance
Inborn Genetic Diseases
Dietary Proteins
Penetrance
Glutens
autoimmune diseases
Linkage Disequilibrium
linkage disequilibrium
gluten
Autoimmune Diseases
dietary protein
Single Nucleotide Polymorphism
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Association analysis of the extended MHC region in Celiac disease implicates multiple independent susceptibility loci. / Ahn, Richard; Ding, Yuan Chun; Murray, Joseph A; Fasano, Alessio; Green, Peter H R; Neuhausen, Susan L.; Garner, Chad.

In: PLoS One, Vol. 7, No. 5, e36926, 17.05.2012.

Research output: Contribution to journalArticle

Ahn, Richard ; Ding, Yuan Chun ; Murray, Joseph A ; Fasano, Alessio ; Green, Peter H R ; Neuhausen, Susan L. ; Garner, Chad. / Association analysis of the extended MHC region in Celiac disease implicates multiple independent susceptibility loci. In: PLoS One. 2012 ; Vol. 7, No. 5.
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