Association Analysis of the Extended MHC Region in Celiac Disease Implicates Multiple Independent Susceptibility Loci

被引：29

作者：

Ahn, Richard ^{[1
]}

Ding, Yuan Chun ^{[2
]}

Murray, Joseph ^{[3
]}

Fasano, Alessio ^{[4
]}

Green, Peter H. R. ^{[5
]}

Neuhausen, Susan L. ^{[2
]}

Garner, Chad ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92717 USA

[2] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA

[3] Mayo Clin, Dept Med & Immunol, Rochester, MN USA

[4] Univ Maryland, Sch Med, Ctr Celiac Res, Baltimore, MD 21201 USA

[5] Columbia Univ, Celiac Dis Ctr, New York, NY USA

来源：

PLOS ONE | 2012年 / 7卷 / 05期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; DERMATITIS-HERPETIFORMIS; HLA-DQ; LINKAGE ANALYSIS; RISK VARIANTS; POPULATION; DISORDERS; GENES; IDENTIFICATION; REPLICATION;

D O I：

10.1371/journal.pone.0036926

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：9

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