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.

Original publication

DOI

10.1073/pnas.0909307106

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

03/11/2009

Volume

106

Pages

18680 - 18685

Keywords

Chromosome Mapping, Databases, Genetic, Genetic Predisposition to Disease, Genetic Testing, HLA Antigens, Humans, Immune System Diseases, Major Histocompatibility Complex, Polymorphism, Single Nucleotide