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Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

Objectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA l... Full description

Journal Title: Annals of the Rheumatic Diseases 2012, Vol.71 (7), p.1117-1121
Main Author: Hinks, Anne
Other Authors: Cobb, Joanna , Sudman, Marc , Eyre, Stephen , Martin, Paul , Flynn, Edward , Packham, Jonathon , Barton, Anne , Worthington, Jane , Langefeld, Carl D , Glass, David N , Thompson, Susan D , Thomson, Wendy
Format: Electronic Article Electronic Article
Language: English
Subjects:
DNA
Publisher: London: BMJ Publishing Group Ltd and European League Against Rheumatism
ID: ISSN: 0003-4967
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recordid: cdi_crossref_primary_10_1136_annrheumdis_2011_200814
title: Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap
format: Article
creator:
  • Hinks, Anne
  • Cobb, Joanna
  • Sudman, Marc
  • Eyre, Stephen
  • Martin, Paul
  • Flynn, Edward
  • Packham, Jonathon
  • Barton, Anne
  • Worthington, Jane
  • Langefeld, Carl D
  • Glass, David N
  • Thompson, Susan D
  • Thomson, Wendy
subjects:
  • 1506
  • Adolescent
  • Arthritis, Juvenile - diagnosis
  • Arthritis, Juvenile - genetics
  • Arthritis, Juvenile - metabolism
  • Autoimmune diseases
  • Biological and medical sciences
  • Care and treatment
  • CD3 Complex - genetics
  • CD3 Complex - metabolism
  • Child
  • Child, Preschool
  • Children & youth
  • Clinical
  • Clinical and Epidemiological Research
  • connective tissue diseases
  • Consortia
  • Deoxyribonucleic acid
  • Diagnosis
  • Disease
  • Disease Progression
  • Diseases of the osteoarticular system
  • DNA
  • Epidemiological Research
  • Ethics
  • eye diseases
  • Gene Frequency
  • Genetic Predisposition to Disease
  • genetic structures
  • Genetic testing
  • Genome-Wide Association Study
  • Genomes
  • Genotype
  • Health risk assessment
  • Hospitals
  • Humans
  • immune system diseases
  • Inflammatory joint diseases
  • Interleukin-2 Receptor alpha Subunit - genetics
  • Interleukin-2 Receptor alpha Subunit - metabolism
  • Medical sciences
  • musculoskeletal diseases
  • Physiological aspects
  • Polymorphism, Single Nucleotide
  • Principal components analysis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism
  • Rheumatoid arthritis
  • Rheumatology
  • Risk factors
  • Single nucleotide polymorphisms
  • skin
  • Studies
  • T cells
  • White people
ispartof: Annals of the Rheumatic Diseases, 2012, Vol.71 (7), p.1117-1121
description: Objectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Results Thirteen SNP showed significant association (p
language: eng
source:
identifier: ISSN: 0003-4967
fulltext: no_fulltext
issn:
  • 0003-4967
  • 1468-2060
url: Link


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titleInvestigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap
creatorHinks, Anne ; Cobb, Joanna ; Sudman, Marc ; Eyre, Stephen ; Martin, Paul ; Flynn, Edward ; Packham, Jonathon ; Barton, Anne ; Worthington, Jane ; Langefeld, Carl D ; Glass, David N ; Thompson, Susan D ; Thomson, Wendy
creatorcontribHinks, Anne ; Cobb, Joanna ; Sudman, Marc ; Eyre, Stephen ; Martin, Paul ; Flynn, Edward ; Packham, Jonathon ; Barton, Anne ; Worthington, Jane ; Langefeld, Carl D ; Glass, David N ; Thompson, Susan D ; Thomson, Wendy ; UK RA Genetics (UKRAG) Consortium ; British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group ; Childhood Arthritis Prospective Study (CAPS)
descriptionObjectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Results Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. Conclusions A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
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subject1506 ; Adolescent ; Arthritis, Juvenile - diagnosis ; Arthritis, Juvenile - genetics ; Arthritis, Juvenile - metabolism ; Autoimmune diseases ; Biological and medical sciences ; Care and treatment ; CD3 Complex - genetics ; CD3 Complex - metabolism ; Child ; Child, Preschool ; Children & youth ; Clinical ; Clinical and Epidemiological Research ; connective tissue diseases ; Consortia ; Deoxyribonucleic acid ; Diagnosis ; Disease ; Disease Progression ; Diseases of the osteoarticular system ; DNA ; Epidemiological Research ; Ethics ; eye diseases ; Gene Frequency ; Genetic Predisposition to Disease ; genetic structures ; Genetic testing ; Genome-Wide Association Study ; Genomes ; Genotype ; Health risk assessment ; Hospitals ; Humans ; immune system diseases ; Inflammatory joint diseases ; Interleukin-2 Receptor alpha Subunit - genetics ; Interleukin-2 Receptor alpha Subunit - metabolism ; Medical sciences ; musculoskeletal diseases ; Physiological aspects ; Polymorphism, Single Nucleotide ; Principal components analysis ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism ; Rheumatoid arthritis ; Rheumatology ; Risk factors ; Single nucleotide polymorphisms ; skin ; Studies ; T cells ; White people
ispartofAnnals of the Rheumatic Diseases, 2012, Vol.71 (7), p.1117-1121
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9Langefeld, Carl D
10Glass, David N
11Thompson, Susan D
12Thomson, Wendy
13UK RA Genetics (UKRAG) Consortium
14British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group
15Childhood Arthritis Prospective Study (CAPS)
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0Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap
1Annals of the Rheumatic Diseases
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descriptionObjectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Results Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. Conclusions A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
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3Arthritis, Juvenile - genetics
4Arthritis, Juvenile - metabolism
5Autoimmune diseases
6Biological and medical sciences
7Care and treatment
8CD3 Complex - genetics
9CD3 Complex - metabolism
10Child
11Child, Preschool
12Children & youth
13Clinical
14Clinical and Epidemiological Research
15connective tissue diseases
16Consortia
17Deoxyribonucleic acid
18Diagnosis
19Disease
20Disease Progression
21Diseases of the osteoarticular system
22DNA
23Epidemiological Research
24Ethics
25eye diseases
26Gene Frequency
27Genetic Predisposition to Disease
28genetic structures
29Genetic testing
30Genome-Wide Association Study
31Genomes
32Genotype
33Health risk assessment
34Hospitals
35Humans
36immune system diseases
37Inflammatory joint diseases
38Interleukin-2 Receptor alpha Subunit - genetics
39Interleukin-2 Receptor alpha Subunit - metabolism
40Medical sciences
41musculoskeletal diseases
42Physiological aspects
43Polymorphism, Single Nucleotide
44Principal components analysis
45Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics
46Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism
47Rheumatoid arthritis
48Rheumatology
49Risk factors
50Single nucleotide polymorphisms
51skin
52Studies
53T cells
54White people
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titleInvestigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap
authorHinks, Anne ; Cobb, Joanna ; Sudman, Marc ; Eyre, Stephen ; Martin, Paul ; Flynn, Edward ; Packham, Jonathon ; Barton, Anne ; Worthington, Jane ; Langefeld, Carl D ; Glass, David N ; Thompson, Susan D ; Thomson, Wendy
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01506
1Adolescent
2Arthritis, Juvenile - diagnosis
3Arthritis, Juvenile - genetics
4Arthritis, Juvenile - metabolism
5Autoimmune diseases
6Biological and medical sciences
7Care and treatment
8CD3 Complex - genetics
9CD3 Complex - metabolism
10Child
11Child, Preschool
12Children & youth
13Clinical
14Clinical and Epidemiological Research
15connective tissue diseases
16Consortia
17Deoxyribonucleic acid
18Diagnosis
19Disease
20Disease Progression
21Diseases of the osteoarticular system
22DNA
23Epidemiological Research
24Ethics
25eye diseases
26Gene Frequency
27Genetic Predisposition to Disease
28genetic structures
29Genetic testing
30Genome-Wide Association Study
31Genomes
32Genotype
33Health risk assessment
34Hospitals
35Humans
36immune system diseases
37Inflammatory joint diseases
38Interleukin-2 Receptor alpha Subunit - genetics
39Interleukin-2 Receptor alpha Subunit - metabolism
40Medical sciences
41musculoskeletal diseases
42Physiological aspects
43Polymorphism, Single Nucleotide
44Principal components analysis
45Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics
46Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism
47Rheumatoid arthritis
48Rheumatology
49Risk factors
50Single nucleotide polymorphisms
51skin
52Studies
53T cells
54White people
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10Glass, David N
11Thompson, Susan D
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13UK RA Genetics (UKRAG) Consortium
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9Langefeld, Carl D
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abstractObjectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Results Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. Conclusions A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
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