Fine Mapping MHC Region Adds New Info on Genetic Risk for Celiac Disease

Celiac.com 06/03/2015 - Although dietary gluten is the trigger for celiac disease, risk is strongly influenced by genetic variation in the major histocompatibility complex (MHC) region.

A team of researchers recently set out to fine map the MHC association signal to identify additional celiac disease risk factors independent of the HLA-DQA1 and HLA-DQB1 alleles. The researchers included J. Gutierrez-Achury, A. Zhernakova, S.L. Pulit, G. Trynka, K.A. Hunt, J. Romanos, S. Raychaudhuri, D.A. van Heel, C. Wijmenga, and P.I. de Bakker.

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Their team fine mapped the MHC association signal looking for risk factors other than the HLA-DQA1 and HLA-DQB1 alleles, and the found 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.

Nailing down exactly what genetic factors influence the heritability of celiac disease will help researchers to better understand the disease, and to develop better treatments and screening options.

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

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