Abstract
ObjectiveCandidate gene association studies and genome-wide association studies (GWAs) have identified a large number of single nucleotide polymorphisms (SNPs) loci affecting susceptibility to rheumatoid arthritis (RA). However, for the same locus, some studies have yielded inconsistent results. To assess all the available evidence for association, we performed a meta-analysis on previously published case-control studies investigating the association between SNPs and RA.MethodsTwo hundred and sixteen studies, involving 125 SNPs, were reviewed. For each SNP, three genetic models were considered: the allele, dominant and recessive effects models. For each model, the effect summary odds ratio (OR) and 95% CIs were calculated. Cochran’s Q-statistics were used to assess heterogeneity. If the heterogeneity was high, a random effects model was used for meta-analysis, otherwise a fixed effects model was used.ResultsThe meta-analysis results showed that: (1) 30, 28 and 26 SNPs were significantly associated with RA (P<0.01) for the allele, dominant, and recessive models, respectively. (2) rs2476601 (PTPN22) showed the strongest association for all the three models: OR = 1.605, 95% CI: 1.540–1.672, P<1.00E−15 for the T-allele; OR = 1.638, 95% CI: 1.565–1.714, P<1.00E−15 for the T/T+T/C genotype and OR = 2.544, 95% CI: 2.173–2.978, P<1.00E−15 for the T/T genotype. (3) Only 23 (18.4%), 13 (10.4%) and 15 (12.0%) SNPs had high heterogeneity (P<0.01) for the three models, respectively. (4) For some of the SNPs, there was no publication bias according to Funnel plots and Egger’s regression tests (P<0.01). For the other SNPs, the associations were tested in only a few studies, and may have been subject to publication bias. More studies on these loci are required.ConclusionOur meta-analysis provides a comprehensive evaluation of the RA association studies from the past two decades. The detailed meta-analysis results are available at: http://210.46.85.180/DRAP/index.php/Metaanalysis/index.
Highlights
Rheumatoid Arthritis (RA) is an autoimmune disease that causes inflammation of the joints and surrounding tissues
(4) For some of the single nucleotide polymorphisms (SNPs), there was no publication bias according to Funnel plots and Egger’s regression tests (P,0.01)
For the other SNPs, the associations were tested in only a few studies, and may have been subject to publication bias
Summary
Rheumatoid Arthritis (RA) is an autoimmune disease that causes inflammation of the joints and surrounding tissues. Its main symptoms are pain, swelling, stiffness and loss of function in the joints [1]. The prevalence of RA is about 1% in the adult population, and is higher among women than men [2]. Complex disease, RA is usually caused by the interaction of multiple genetic variants and environmental factors [3]. The contribution of genetic factors is estimated to account for about 50–65% of the risk of developing RA [4,5]. The identification of genetic factors is important for understanding the pathogenesis of RA
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