OBJECTIVE: To test for associations between non-major histocompatibility complex susceptibility loci previously reported in autoimmune diseases and juvenile idiopathic arthritis (JIA). METHODS: Published autoimmune disease genome-wide association studies were reviewed, and 519 single-nucleotide polymorphisms (SNPs) were selected for association testing. The initial cohort included 809 JIA cases and 3,535 controls of non-Hispanic, European ancestry. Of the SNPs, 257 were successfully genotyped, while 168 were imputed with quality. Based on findings in the initial cohort, replication was sought for 21 SNPs in a second cohort of 1,015 JIA cases and 1,569 controls collected in the US and Germany. For the initial cohort, tests for association were adjusted for potential confounding effects of population structure by including principal components derived from a genome-wide association study as covariates in logistic regression models. Odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Testing for association of previously reported autoimmune disease genetic associations in the initial cohort suggested associations with JIA in 13 distinct loci. Of these, 7 were validated in the replication cohort. Meta-analysis results for the replicating loci included PTPN22 (rs6679677 [OR 1.58, P = 1.98 × 10(-12) ], rs2476601 [OR 1.64, P = 1.90 × 10(-13) ], and rs2488457 [OR 1.32, P = 6.74 × 10(-8) ]), PTPN2 (rs1893217 [OR = 1.33, P = 1.60 × 10(-9) ] and rs7234029 [OR 1.35, P = 1.86 × 10(-10) ]), ADAD1-IL2-IL21 (rs17388568 [OR 1.24, P = 1.13 × 10(-6) ] and rs13143866 [OR 0.83, P = 1.95 × 10(-4) ]), STAT4 (rs3821236 [OR = 1.27, P = 2.36 × 10(-6) ] and rs7574865 [OR = 1.31, P = 2.21 × 10(-6) ]), C12orf30 (rs17696736 [OR = 1.19, P = 2.59 × 10(-5) ]), COG6 (rs7993214 [OR = 0.76, P = 1.10 × 10(-5) ]), and ANGPT1 (rs1010824 [OR = 0.79, P = 2.91 × 10(-4) ]). These polymorphisms have been reported in diseases such as rheumatoid arthritis, type 1 diabetes mellitus, Crohn's disease, and multiple sclerosis. CONCLUSION: General susceptibility loci for autoimmunity are shared across diseases, including JIA, suggesting the potential for common therapeutic targets and mechanisms.
OBJECTIVE: To test for associations between non-major histocompatibility complex susceptibility loci previously reported in autoimmune diseases and juvenile idiopathic arthritis (JIA). METHODS: Published autoimmune disease genome-wide association studies were reviewed, and 519 single-nucleotide polymorphisms (SNPs) were selected for association testing. The initial cohort included 809 JIA cases and 3,535 controls of non-Hispanic, European ancestry. Of the SNPs, 257 were successfully genotyped, while 168 were imputed with quality. Based on findings in the initial cohort, replication was sought for 21 SNPs in a second cohort of 1,015 JIA cases and 1,569 controls collected in the US and Germany. For the initial cohort, tests for association were adjusted for potential confounding effects of population structure by including principal components derived from a genome-wide association study as covariates in logistic regression models. Odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Testing for association of previously reported autoimmune disease genetic associations in the initial cohort suggested associations with JIA in 13 distinct loci. Of these, 7 were validated in the replication cohort. Meta-analysis results for the replicating loci included PTPN22 (rs6679677 [OR 1.58, P = 1.98 × 10(-12) ], rs2476601 [OR 1.64, P = 1.90 × 10(-13) ], and rs2488457 [OR 1.32, P = 6.74 × 10(-8) ]), PTPN2 (rs1893217 [OR = 1.33, P = 1.60 × 10(-9) ] and rs7234029 [OR 1.35, P = 1.86 × 10(-10) ]), ADAD1-IL2-IL21 (rs17388568 [OR 1.24, P = 1.13 × 10(-6) ] and rs13143866 [OR 0.83, P = 1.95 × 10(-4) ]), STAT4 (rs3821236 [OR = 1.27, P = 2.36 × 10(-6) ] and rs7574865 [OR = 1.31, P = 2.21 × 10(-6) ]), C12orf30 (rs17696736 [OR = 1.19, P = 2.59 × 10(-5) ]), COG6 (rs7993214 [OR = 0.76, P = 1.10 × 10(-5) ]), and ANGPT1 (rs1010824 [OR = 0.79, P = 2.91 × 10(-4) ]). These polymorphisms have been reported in diseases such as rheumatoid arthritis, type 1 diabetes mellitus, Crohn's disease, and multiple sclerosis. CONCLUSION: General susceptibility loci for autoimmunity are shared across diseases, including JIA, suggesting the potential for common therapeutic targets and mechanisms.
Authors: Sampath Prahalad; Sterling Hansen; April Whiting; Stephen L Guthery; Bronte Clifford; Bernadette McNally; Andrew S Zeft; John F Bohnsack; Lynn B Jorde Journal: Arthritis Rheum Date: 2009-07
Authors: H M Albers; F A S Kurreeman; J J Houwing-Duistermaat; D M C Brinkman; S S M Kamphuis; H J Girschick; C Wouters; M A J Van Rossum; W Verduijn; R E M Toes; T W J Huizinga; M W Schilham; R ten Cate Journal: Ann Rheum Dis Date: 2008-07-01 Impact factor: 19.103
Authors: H M Albers; F A S Kurreeman; G Stoeken-Rijsbergen; D M C Brinkman; S S M Kamphuis; M A J van Rossum; H J Girschick; C Wouters; R K Saurenmann; E Hoppenreijs; P Slagboom; J J Houwing-Duistermaat; W Verduijn; T W J Huizinga; R Ten Cate; R E M Toes; M W Schilham Journal: Arthritis Rheum Date: 2009-03
Authors: Peter K Gregersen; Chistopher I Amos; Annette T Lee; Yue Lu; Elaine F Remmers; Daniel L Kastner; Michael F Seldin; Lindsey A Criswell; Robert M Plenge; V Michael Holers; Ted R Mikuls; Tuulikki Sokka; Larry W Moreland; S Louis Bridges; Gang Xie; Ann B Begovich; Katherine A Siminovitch Journal: Nat Genet Date: 2009-06-07 Impact factor: 38.330
Authors: Soumya Raychaudhuri; Elaine F Remmers; Annette T Lee; Rachel Hackett; Candace Guiducci; Noël P Burtt; Lauren Gianniny; Benjamin D Korman; Leonid Padyukov; Fina A S Kurreeman; Monica Chang; Joseph J Catanese; Bo Ding; Sandra Wong; Annette H M van der Helm-van Mil; Benjamin M Neale; Jonathan Coblyn; Jing Cui; Paul P Tak; Gert Jan Wolbink; J Bart A Crusius; Irene E van der Horst-Bruinsma; Lindsey A Criswell; Christopher I Amos; Michael F Seldin; Daniel L Kastner; Kristin G Ardlie; Lars Alfredsson; Karen H Costenbader; David Altshuler; Tom W J Huizinga; Nancy A Shadick; Michael E Weinblatt; Niek de Vries; Jane Worthington; Mark Seielstad; Rene E M Toes; Elizabeth W Karlson; Ann B Begovich; Lars Klareskog; Peter K Gregersen; Mark J Daly; Robert M Plenge Journal: Nat Genet Date: 2008-09-14 Impact factor: 38.330
Authors: Anne Hinks; Xiayi Ke; Anne Barton; Steve Eyre; John Bowes; Jane Worthington; Susan D Thompson; Carl D Langefeld; David N Glass; Wendy Thomson Journal: Arthritis Rheum Date: 2009-01
Authors: Anne Hinks; Anne Barton; Neil Shephard; Steve Eyre; John Bowes; Michele Cargill; Eric Wang; Xiayi Ke; Giulia C Kennedy; Sally John; Jane Worthington; Wendy Thomson Journal: Arthritis Rheum Date: 2009-01
Authors: Mark S Silverberg; Judy H Cho; John D Rioux; Dermot P B McGovern; Jing Wu; Vito Annese; Jean-Paul Achkar; Philippe Goyette; Regan Scott; Wei Xu; M Michael Barmada; Lambertus Klei; Mark J Daly; Clara Abraham; Theodore M Bayless; Fabrizio Bossa; Anne M Griffiths; Andrew F Ippoliti; Raymond G Lahaie; Anna Latiano; Pierre Paré; Deborah D Proctor; Miguel D Regueiro; A Hillary Steinhart; Stephan R Targan; L Philip Schumm; Emily O Kistner; Annette T Lee; Peter K Gregersen; Jerome I Rotter; Steven R Brant; Kent D Taylor; Kathryn Roeder; Richard H Duerr Journal: Nat Genet Date: 2009-01-04 Impact factor: 38.330
Authors: 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 Journal: Arthritis Rheum Date: 2012-10
Authors: Laura A McIntosh; Miranda C Marion; Marc Sudman; Mary E Comeau; Mara L Becker; John F Bohnsack; Tasha E Fingerlin; Thomas A Griffin; J Peter Haas; Daniel J Lovell; Lisa A Maier; Peter A Nigrovic; Sampath Prahalad; Marilynn Punaro; Carlos D Rosé; Carol A Wallace; Carol A Wise; Halima Moncrieffe; Timothy D Howard; Carl D Langefeld; Susan D Thompson Journal: Arthritis Rheumatol Date: 2017-10-12 Impact factor: 10.995
Authors: Shaunak S Adkar; Jonathan M Brunger; Vincent P Willard; Chia-Lung Wu; Charles A Gersbach; Farshid Guilak Journal: Trends Mol Med Date: 2017-09-05 Impact factor: 11.951
Authors: Shepherd H Schurman; Terrance P O'Hanlon; John A McGrath; Artiom Gruzdev; Arsun Bektas; Hong Xu; Stavros Garantziotis; Darryl C Zeldin; Frederick W Miller Journal: J Autoimmun Date: 2019-11-21 Impact factor: 7.094