title: Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis.
abstract: 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) ).
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California, San Francisco, CA, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Chung
authors.forename: Gang
authors.initials: G
authors.lastname: Xie
authors.forename: Delnaz
authors.initials: D
authors.lastname: Roshandel
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Edberg
authors.forename: Megan
authors.initials: M
authors.lastname: Kravitz
authors.forename: Paul F
authors.initials: PF
authors.lastname: Dellaripa
authors.forename: Gary S
authors.initials: GS
authors.lastname: Hoffman
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Mahr
authors.forename: Philip
authors.initials: P
authors.lastname: Seo
authors.forename: Ulrich
authors.initials: U
authors.lastname: Specks
authors.forename: Robert F
authors.initials: RF
authors.lastname: Spiera
authors.forename: E William
authors.initials: EW
authors.lastname: St Clair
authors.forename: John H
authors.initials: JH
authors.lastname: Stone
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014890:Granulomatosis with Polyangiitis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors