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Immunogenetics of Celiac Disease

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Celiac Disease

Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Celiac disease (CD) is a model for common complex disorders with a high degree of heritability. The human leukocyte antigen (HLA) DQ genotype, specifically HLA-DQ2 and HLA-DQ8, is the strongest genetic risk factor. Genome-wide association studies (GWAS) have identified 57 single nucleotide polymorphisms (SNPs) located in the associated 39 non-HLA regions with mainly immunological functions. Together with HLA, these regions explain approximately 54 % of the disease’s heritability. Molecular functional analyses are necessary to delineate the true causal genetic variants and the pathways involved. Since CD shares many of its genetic susceptibility regions and implicated pathways with other immune-related diseases, a combined analysis may discover more common genetic variants with smaller effect sizes. HLA-DQ genotyping can already be used to exclude a diagnosis of CD, for example, as a test in the screening of individuals from high-risk groups, such as patients with type 1 diabetes or autoimmune thyroiditis, and first-degree relatives of CD patients. Discovering more genetic susceptibility variants and the pathways involved may ultimately contribute to risk stratification for follow-up and treatment, and lead to new therapeutic targets.

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Acknowledgments

We thank Jackie Senior for editing the manuscript.

Funding

Work in the Wijmenga group is supported by grants from the Celiac Disease Consortium (an innovative cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government (grant BSIK03009 to CW)) and the Dutch Digestive Disease Foundation (MLDS WO11-30 to CW).

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Authors and Affiliations

  1. Department of Genetics, University Medical Center Groningen, University of Groningen, 30.001, 9700 RB, Groningen, The Netherlands

    Esther C. de Haas M.D. Ph.D., Vinod Kumar Ph.D. & Cisca Wijmenga Ph.D.

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  1. Esther C. de Haas M.D. Ph.D.
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  2. Vinod Kumar Ph.D.
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  3. Cisca Wijmenga Ph.D.
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Corresponding author

Correspondence to Esther C. de Haas M.D. Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

    S. Devi Rampertab

  2. Department of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Gerard E. Mullin

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de Haas, E.C., Kumar, V., Wijmenga, C. (2014). Immunogenetics of Celiac Disease. In: Rampertab, S., Mullin, G. (eds) Celiac Disease. Clinical Gastroenterology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8560-5_5

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  • DOI: https://doi.org/10.1007/978-1-4614-8560-5_5

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