Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 44, Pages 18680-18685Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0909307106
Keywords
autoimmunity; genes; genetics
Categories
Funding
- National Institutes of Allergy and Infectious Diseases [AI067152]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK064869, DK062432]
- National Institute of Neurological Disease and Stroke [NS21799]
- Swedish National Research Counci
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02]
- National Center for Research Resources [U54 RR020278]
- MRC [G0000934] Funding Source: UKRI
- Medical Research Council [G0000934] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10335] Funding Source: researchfish
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The human MHC represents the strongest susceptibility locus for autoimmune diseases. However, the identification of the true predisposing gene(s) has been handicapped by the strong linkage disequilibrium across the region. Furthermore, most studies to date have been limited to the examination of a subset of the HLA and non-HLA genes with a marker density and sample size insufficient for mapping all independent association signals. We genotyped a panel of 1,472 SNPs to capture the common genomic variation across the 3.44 megabase (Mb) classic MHC region in 10,576 DNA samples derived from patients with systemic lupus erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate control samples. We identified the primary association signals for each disease and performed conditional regression to identify independent secondary signals. The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region.
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