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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 3/2010

Open Access 01-06-2010 | Research article

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844with rheumatoid arthritis at a genome-wide level of significance

Authors: Jade E Hollis-Moffatt, Michael Chen-Xu, Ruth Topless, Nicola Dalbeth, Peter J Gow, Andrew A Harrison, John Highton, Peter BB Jones, Michael Nissen, Malcolm D Smith, Andre van Rij, Gregory T Jones, Lisa K Stamp, Tony R Merriman

Published in: Arthritis Research & Therapy | Issue 3/2010

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Abstract

Introduction

The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus.

Methods

A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA.

Results

No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR) = 0.95 (0.80 to 1.12), P = 0.54), or rs17388568 (OR = 1.03 (0.90 to 1.19), P = 0.65) or rs907715 (OR = 0.98 (0.86 to 1.12), P = 0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR = 0.86 (0.82 to 0.91), P = 8.8 × 10-8, P = 2.1 × 10-8 including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR = 1.03, (0.98 to 1.09); P = 0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR = 0.93 (0.87 to 1.00), P = 0.07). However, this trend was not independent of the association at rs6822844.

Conclusions

The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P ≤ 5 ×10-8) level of support for association with RA. As for most other autoimmune diseases, with the notable exception of T1D, rs6822844 is the dominant association in the locus. The KIAA1109-TENR-IL2-IL21 locus also confers susceptibility to other autoimmune phenotypes with a heterogeneous pattern of association.
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Metadata
Title
Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844with rheumatoid arthritis at a genome-wide level of significance
Authors
Jade E Hollis-Moffatt
Michael Chen-Xu
Ruth Topless
Nicola Dalbeth
Peter J Gow
Andrew A Harrison
John Highton
Peter BB Jones
Michael Nissen
Malcolm D Smith
Andre van Rij
Gregory T Jones
Lisa K Stamp
Tony R Merriman
Publication date
01-06-2010
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2010
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3053

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