Published by the University of Chicago Press
Title Analysis of Families in the Multiple Autoimmune Disease Genetics Consortium (MADGC) Collection: the PTPN22 620W Allele Associates with Multiple Autoimmune Phenotypes
Author(s) Lindsey A. Criswell, Kirsten A. Pfeiffer, Raymond F. Lum, Bonnie Gonzales, Jill Novitzke, Marlena Kern, Kathy L. Moser, Ann B. Begovich, Victoria E. H. Carlton, Wentian Li, Annette T. Lee, Ward Ortmann, Timothy W. Behrens, and Peter K. Gregersen
Identifiers The American Journal of Human Genetics, volume 76 (2005), pages 561â€“571
PubMed ID: 15719322
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Copyright Â© 2005, The American Society of Human Genetics.
Abstract Autoimmune disorders constitute a diverse group of phenotypes with overlapping features and a tendency toward familial aggregation. It is likely that common underlying genes are involved in these disorders. Until very recently, no specific allelesaside from a few common human leukocyte antigen class II geneshad been identified that clearly associate with multiple different autoimmune diseases. In this study, we describe a unique collection of 265 multiplex families assembled by the Multiple Autoimmune Disease Genetics Consortium (MADGC). At least two of nine "core" autoimmune diseases are present in each of these families. These core diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease), juvenile RA, inflammatory bowel disease (Crohn disease or ulcerative colitis), psoriasis, and primary SjÃ¶gren syndrome. We report that a recently described functional single-nucleotide polymorphism (rs2476601, encoding R620W) in the intracellular tyrosine phosphatase (PTPN22) confers risk of four separate autoimmune phenotypes in these families: T1D, RA, SLE, and Hashimoto thyroiditis. MS did not show association with the PTPN22 risk allele. These findings suggest a common underlying etiologic pathway for some, but not all, autoimmune disorders, and they suggest that MS may have a pathogenesis that is distinct from RA, SLE, and T1D. DNA and clinical data for the MADGC families are available to the scientific community; these data will provide a valuable resource for the dissection of the complex genetic factors that underlie the various autoimmune phenotypes.