Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

Affiliations

¹ Department of Genetics, University Medical Center, University of Groningen, Groningen, the Netherlands.
² Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
³ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
⁴ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [4] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
⁶ 1] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

PMID: 25894500
PMCID: PMC4449296
DOI: 10.1038/ng.3268

Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

Javier Gutierrez-Achury et al. Nat Genet. 2015 Jun.

. 2015 Jun;47(6):577-8.

doi: 10.1038/ng.3268. Epub 2015 Apr 20.

Affiliations

¹ Department of Genetics, University Medical Center, University of Groningen, Groningen, the Netherlands.
² Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
³ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
⁴ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA. [4] Arthritis Research UK Epidemiology Unit, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
⁶ 1] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands. [2] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

PMID: 25894500
PMCID: PMC4449296
DOI: 10.1038/ng.3268

Abstract

Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region. We fine mapped the MHC association signal to identify additional risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles and observed five new associations that account for 18% of the genetic risk. Taking these new loci together with the 57 known non-MHC loci, genetic variation can now explain up to 48% of celiac disease heritability.

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Figures

**Figure 1**
Schematic representation of the stepwise analysis applied in fine-mapping the HLA region. *HLA-DQA1* and *HLA-DQB1* 4-digit alleles were included in the model to control for their effect (red arrow). A green flag represents each of the steps in the analysis and an independent association.

See this image and copyright information in PMC

References

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Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

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Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease

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