Open AccessMeta‐analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis
Author(s) -
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.,
St.Clair E. William,
Stone John H.,
Plenge Robert M.,
Siminovitch Katherine A.,
Merkel Peter A.,
Monach Paul A.
Publication year - 2012
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.34496
Subject(s) - single nucleotide polymorphism , genetic predisposition , granulomatosis with polyangiitis , medicine , odds ratio , rheumatoid arthritis , immunology , genotype , disease , vasculitis , genetics , biology , gene
Objective To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA. Methods Genetic data from 2 cohorts were meta‐analyzed. Genotypes for 168 previously identified single‐nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single‐marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), 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 (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.70–0.89, P = 9.8 × 10 −5 ). The genetic risk score for RA 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 = 5.1 × 10 −5 ). Conclusion RA 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 significantly associated with GPA in this study.