Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study

Gisela Orozco, Steve Eyre, Anne Hinks, Xiayi Ke, Anthony G Wilson, Deborah E Bax, Ann W Morgan, Paul Emery, Sophia Steer, Lynne Hocking, David M Reid, Paul Wordsworth, Pille Harrison, Wendy Thomson, Anne Barton, Jane Worthington, Wellcome Trust Case Control consortium YEAR Consortium

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Abstract

OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.
Original languageEnglish
Pages (from-to)813-816
Number of pages4
JournalAnnals of the Rheumatic Diseases
Volume69
Issue number5
DOIs
Publication statusPublished - May 2010

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Case-Control Studies
Rheumatoid Arthritis
Genes
Polymorphism
Nucleotides
Population
Single Nucleotide Polymorphism
Meta-Analysis
Genome-Wide Association Study
Genotype

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Orozco, G., Eyre, S., Hinks, A., Ke, X., Wilson, A. G., Bax, D. E., ... Wellcome Trust Case Control consortium YEAR Consortium (2010). Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. Annals of the Rheumatic Diseases, 69(5), 813-816. https://doi.org/10.1136/ard.2009.109579

Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. / Orozco, Gisela; Eyre, Steve; Hinks, Anne; Ke, Xiayi; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane; Wellcome Trust Case Control consortium YEAR Consortium.

In: Annals of the Rheumatic Diseases, Vol. 69, No. 5, 05.2010, p. 813-816.

Research output: Contribution to journalArticle

Orozco, G, Eyre, S, Hinks, A, Ke, X, Wilson, AG, Bax, DE, Morgan, AW, Emery, P, Steer, S, Hocking, L, Reid, DM, Wordsworth, P, Harrison, P, Thomson, W, Barton, A, Worthington, J & Wellcome Trust Case Control consortium YEAR Consortium 2010, 'Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study', Annals of the Rheumatic Diseases, vol. 69, no. 5, pp. 813-816. https://doi.org/10.1136/ard.2009.109579
Orozco, Gisela ; Eyre, Steve ; Hinks, Anne ; Ke, Xiayi ; Wilson, Anthony G ; Bax, Deborah E ; Morgan, Ann W ; Emery, Paul ; Steer, Sophia ; Hocking, Lynne ; Reid, David M ; Wordsworth, Paul ; Harrison, Pille ; Thomson, Wendy ; Barton, Anne ; Worthington, Jane ; Wellcome Trust Case Control consortium YEAR Consortium. / Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. In: Annals of the Rheumatic Diseases. 2010 ; Vol. 69, No. 5. pp. 813-816.
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title = "Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study",
abstract = "OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95{\%} CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95{\%} CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95{\%} CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.",
author = "Gisela Orozco and Steve Eyre and Anne Hinks and Xiayi Ke and Wilson, {Anthony G} and Bax, {Deborah E} and Morgan, {Ann W} and Paul Emery and Sophia Steer and Lynne Hocking and Reid, {David M} and Paul Wordsworth and Pille Harrison and Wendy Thomson and Anne Barton and Jane Worthington and {Wellcome Trust Case Control consortium YEAR Consortium}",
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TY - JOUR

T1 - Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study

AU - Orozco, Gisela

AU - Eyre, Steve

AU - Hinks, Anne

AU - Ke, Xiayi

AU - Wilson, Anthony G

AU - Bax, Deborah E

AU - Morgan, Ann W

AU - Emery, Paul

AU - Steer, Sophia

AU - Hocking, Lynne

AU - Reid, David M

AU - Wordsworth, Paul

AU - Harrison, Pille

AU - Thomson, Wendy

AU - Barton, Anne

AU - Worthington, Jane

AU - Wellcome Trust Case Control consortium YEAR Consortium

PY - 2010/5

Y1 - 2010/5

N2 - OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.

AB - OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.

U2 - 10.1136/ard.2009.109579

DO - 10.1136/ard.2009.109579

M3 - Article

C2 - 19435719

VL - 69

SP - 813

EP - 816

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 5

ER -