Meta-analysis in granulomatosis with polyangiitis reveals shared susceptibility loci with rheumatoid arthritis by Chung Sharon A, Xie Gang, Roshandel Delnaz, Sherva Richard, Edberg Jeffrey C, Kravitz Megan, Dellaripa Paul F, Hoffman Gary S, Mahr Alfred D, Seo Philip, Specks Ulrich, Spiera Robert F, William St Clair E, Stone John H, Plenge Robert M, Siminovitch Katherine A, Merkel Peter A, Monach Paul A in Arthritis and rheumatism (2012). PubMed

Abstract

OBJECTIVES: To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis), and determine whether genetic susceptibility profiles of other autoimmune diseases are associated with GPA METHODS: Genetic data from two cohorts were meta-analyzed. Genotypes for 168 previously identified single nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained for a total of 880 GPA cases and 1969 controls of European descent. Single marker associations were identified using additive logistic regression models. Multi-SNP associations with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses using ancestry informative markers and principal components analysis. RESULTS: Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (OR 0.79. 95% CI 0.70-0.89, p=9.8×10(-5) ). A genetic risk score based on rheumatoid arthritis susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.02-1.08, p=5.1x10(-5) ). CONCLUSIONS: Rheumatoid arthritis and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically associated with GPA in this study. © 2012 American College of Rheumatology.

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