The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1

Susan D. Thompson, Marc Sudman, Paula S. Ramos, Miranda C. Marion, Mary Ryan, Monica Tsoras, Tracey Weiler, Michael Wagner, Mehdi Keddache, J. Peter Haas, Cornelia Mueller, Sampath Prahalad, John Bohnsack, Carol A. Wise, Marilynn Punaro, Dongping Zhang, Carlos D. Rosé, Mary E. Comeau, Jasmin Divers, David N. GlassCarl D. Langefeld

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3265-3276
Number of pages12
JournalArthritis and Rheumatism
Volume62
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Juvenile Arthritis
Autoimmune Diseases
Odds Ratio
Single Nucleotide Polymorphism
Genome-Wide Association Study
Logistic Models
Major Histocompatibility Complex
Autoimmunity
Type 1 Diabetes Mellitus
Crohn Disease
Multiple Sclerosis
Interleukin-2
Germany
Meta-Analysis
Rheumatoid Arthritis

ASJC Scopus subject areas

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

Cite this

Thompson, S. D., Sudman, M., Ramos, P. S., Marion, M. C., Ryan, M., Tsoras, M., ... Langefeld, C. D. (2010). The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. Arthritis and Rheumatism, 62(11), 3265-3276. https://doi.org/10.1002/art.27688

The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. / Thompson, Susan D.; Sudman, Marc; Ramos, Paula S.; Marion, Miranda C.; Ryan, Mary; Tsoras, Monica; Weiler, Tracey; Wagner, Michael; Keddache, Mehdi; Haas, J. Peter; Mueller, Cornelia; Prahalad, Sampath; Bohnsack, John; Wise, Carol A.; Punaro, Marilynn; Zhang, Dongping; Rosé, Carlos D.; Comeau, Mary E.; Divers, Jasmin; Glass, David N.; Langefeld, Carl D.

In: Arthritis and Rheumatism, Vol. 62, No. 11, 11.2010, p. 3265-3276.

Research output: Contribution to journalArticle

Thompson, SD, Sudman, M, Ramos, PS, Marion, MC, Ryan, M, Tsoras, M, Weiler, T, Wagner, M, Keddache, M, Haas, JP, Mueller, C, Prahalad, S, Bohnsack, J, Wise, CA, Punaro, M, Zhang, D, Rosé, CD, Comeau, ME, Divers, J, Glass, DN & Langefeld, CD 2010, 'The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1', Arthritis and Rheumatism, vol. 62, no. 11, pp. 3265-3276. https://doi.org/10.1002/art.27688
Thompson, Susan D. ; Sudman, Marc ; Ramos, Paula S. ; Marion, Miranda C. ; Ryan, Mary ; Tsoras, Monica ; Weiler, Tracey ; Wagner, Michael ; Keddache, Mehdi ; Haas, J. Peter ; Mueller, Cornelia ; Prahalad, Sampath ; Bohnsack, John ; Wise, Carol A. ; Punaro, Marilynn ; Zhang, Dongping ; Rosé, Carlos D. ; Comeau, Mary E. ; Divers, Jasmin ; Glass, David N. ; Langefeld, Carl D. / The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. In: Arthritis and Rheumatism. 2010 ; Vol. 62, No. 11. pp. 3265-3276.
@article{5e075fb4089b4cf3a7b07dca6e8faa66,
title = "The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1",
abstract = "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.",
author = "Thompson, {Susan D.} and Marc Sudman and Ramos, {Paula S.} and Marion, {Miranda C.} and Mary Ryan and Monica Tsoras and Tracey Weiler and Michael Wagner and Mehdi Keddache and Haas, {J. Peter} and Cornelia Mueller and Sampath Prahalad and John Bohnsack and Wise, {Carol A.} and Marilynn Punaro and Dongping Zhang and Ros{\'e}, {Carlos D.} and Comeau, {Mary E.} and Jasmin Divers and Glass, {David N.} and Langefeld, {Carl D.}",
year = "2010",
month = "11",
doi = "10.1002/art.27688",
language = "English (US)",
volume = "62",
pages = "3265--3276",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "11",

}

TY - JOUR

T1 - The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1

AU - Thompson, Susan D.

AU - Sudman, Marc

AU - Ramos, Paula S.

AU - Marion, Miranda C.

AU - Ryan, Mary

AU - Tsoras, Monica

AU - Weiler, Tracey

AU - Wagner, Michael

AU - Keddache, Mehdi

AU - Haas, J. Peter

AU - Mueller, Cornelia

AU - Prahalad, Sampath

AU - Bohnsack, John

AU - Wise, Carol A.

AU - Punaro, Marilynn

AU - Zhang, Dongping

AU - Rosé, Carlos D.

AU - Comeau, Mary E.

AU - Divers, Jasmin

AU - Glass, David N.

AU - Langefeld, Carl D.

PY - 2010/11

Y1 - 2010/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78249237207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78249237207&partnerID=8YFLogxK

U2 - 10.1002/art.27688

DO - 10.1002/art.27688

M3 - Article

C2 - 20722033

AN - SCOPUS:78249237207

VL - 62

SP - 3265

EP - 3276

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 11

ER -