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We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Original publication

DOI

10.1038/ng.2007.17

Type

Journal article

Journal

Nat Genet

Publication Date

11/2007

Volume

39

Pages

1329 - 1337

Keywords

Aminopeptidases, Autoimmunity, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Genetics, Population, Genotype, Haplotypes, Humans, Linkage Disequilibrium, Minor Histocompatibility Antigens, Multiple Sclerosis, North America, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptors, Immunologic, Receptors, Interleukin, Spondylitis, Ankylosing, Thyroiditis, Autoimmune