Dataset Information

Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.

ABSTRACT: OBJECTIVE:Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2-IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using data from previously published studies. METHODS:We evaluated case-control associations between rs6822844 and celiac disease (CD) in subjects from Argentina; rheumatoid arthritis (RA), type 1 diabetes mellitus (DM), primary Sjögren's syndrome (SS), and systemic lupus erythematosus (SLE) in subjects from Colombia; and Behçet's disease (BD) in subjects from Turkey. Allele and gene distributions were compared between cases and controls. Meta-analyses were performed using data from the present study and previous studies. RESULTS:We detected significant associations of rs6822844 with SLE (P = 0.008), type 1 DM (P = 0.014), RA (P = 0.019), and primary SS (P = 0.033) but not with BD (P = 0.34) or CD (P = 0.98). We identified little evidence of population differentiation (F(ST) = 0.01) within cases and controls from Argentina and Colombia, suggesting that association was not influenced by population substructure. Disease-specific meta-analysis indicated significant association for RA (P(meta) = 3.61 x 10(-6)), inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) (P(meta) = 3.48 x 10(-12)), type 1 DM (P(meta) = 5.33 x 10(-5)), and CD (P(meta) = 5.30 x 10(-3)). Overall meta-analysis across all autoimmune diseases reinforced association with rs6822844 (23 data sets; P(meta) = 2.61 x 10(-25), odds ratio 0.73 [95% confidence interval 0.69-0.78]). CONCLUSION:Our results indicate that there is an association between rs6822844 and multiple autoimmune diseases in non-European populations. Meta-analysis results strongly reinforce this robust association across multiple autoimmune diseases in both European-derived and non-European populations.

SUBMITTER: Maiti AK

PROVIDER: S-EPMC3028384 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.

Maiti Amit K AK Kim-Howard Xana X Viswanathan Parvathi P Guillén Laura L Rojas-Villarraga Adriana A Deshmukh Harshal H Direskeneli Haner H Saruhan-Direskeneli Güher G Cañas Carlos C Tobön Gabriel J GJ Sawalha Amr H AH Cherñavsky Alejandra C AC Anaya Juan-Manuel JM Nath Swapan K SK

Arthritis and rheumatism 20100201 2

<h4>Objective</h4>Autoimmune diseases often have susceptibility genes in common, indicating similar molecular mechanisms. Increasing evidence suggests that rs6822844 at the IL2-IL21 region is strongly associated with multiple autoimmune diseases in individuals of European descent. This study was undertaken to attempt to replicate the association between rs6822844 and 6 different immune-mediated diseases in non-European populations, and to perform disease-specific and overall meta-analyses using ...[more]

PMID: 20112382

Similar Datasets

Project description:IntroductionThe 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.MethodsA 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.ResultsNo 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=8.8x10(-8), P=2.1x10(-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.ConclusionsThe 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<or=5x10(-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.

Dataset Information

Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.

Publications

Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets