Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis

Sharon A. Chung, Gang Xie, Delnaz Roshandel, Richard Sherva, Jeffrey C. Edberg, Megan Kravitz, Paul F. Dellaripa, Gary S. Hoffman, Alfred D. Mahr, Philip Seo, Ulrich Specks, Robert F. Spiera, E. William St.Clair, John H. Stone, Robert M. Plenge, Katherine A. Siminovitch, Peter A. Merkel, Paul A. Monach

Research output: Contribution to journalArticle

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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 metaanalyzed. Genotypes for 168 previously identified singlenucleotide 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. Singlemarker 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.

Original languageEnglish (US)
Pages (from-to)3463-3471
Number of pages9
JournalArthritis and Rheumatism
Volume64
Issue number10
DOIs
StatePublished - Oct 2012

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Granulomatosis with Polyangiitis
Genetic Polymorphisms
Autoimmune Diseases
Meta-Analysis
Rheumatoid Arthritis
Genetic Predisposition to Disease
Logistic Models
Odds Ratio
Confidence Intervals
Disease Susceptibility
Celiac Disease
Principal Component Analysis
Type 1 Diabetes Mellitus
Ulcerative Colitis
Crohn Disease
Systemic Lupus Erythematosus
Genotype
Population

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis. / 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.

In: Arthritis and Rheumatism, Vol. 64, No. 10, 10.2012, p. 3463-3471.

Research output: Contribution to journalArticle

Chung, SA, Xie, G, Roshandel, D, Sherva, R, Edberg, JC, Kravitz, M, Dellaripa, PF, Hoffman, GS, Mahr, AD, Seo, P, Specks, U, Spiera, RF, St.Clair, EW, Stone, JH, Plenge, RM, Siminovitch, KA, Merkel, PA & Monach, PA 2012, 'Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis', Arthritis and Rheumatism, vol. 64, no. 10, pp. 3463-3471. https://doi.org/10.1002/art.34496
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. / Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis. In: Arthritis and Rheumatism. 2012 ; Vol. 64, No. 10. pp. 3463-3471.
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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 metaanalyzed. Genotypes for 168 previously identified singlenucleotide 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. Singlemarker 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.",
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T1 - Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis

AU - Chung, Sharon A.

AU - Xie, Gang

AU - Roshandel, Delnaz

AU - Sherva, Richard

AU - Edberg, Jeffrey C.

AU - Kravitz, Megan

AU - Dellaripa, Paul F.

AU - Hoffman, Gary S.

AU - Mahr, Alfred D.

AU - Seo, Philip

AU - Specks, Ulrich

AU - Spiera, Robert F.

AU - St.Clair, E. William

AU - Stone, John H.

AU - Plenge, Robert M.

AU - Siminovitch, Katherine A.

AU - Merkel, Peter A.

AU - Monach, Paul A.

PY - 2012/10

Y1 - 2012/10

N2 - 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 metaanalyzed. Genotypes for 168 previously identified singlenucleotide 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. Singlemarker 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.

AB - 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 metaanalyzed. Genotypes for 168 previously identified singlenucleotide 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. Singlemarker 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.

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