Meta-Analysis of 125 Rheumatoid Arthritis-Related Single Nucleotide Polymorphisms Studied in the Past Two Decades

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.

Association of Interleukin‐1 beta and tumor necrosis factor‐alpha genetic polymorphisms with gastric cancer in India

“…To evaluate the heterogeneity of between-and within-study variation, Cochran's Q test was employed [Huedo-Medina et al, 2006] (p < 0.1). To measure the degree of inconsistency across studies another indicator of heterogeneity called I 2 was used where values of this variable greater than 25%, 50% or 75% indicated low-, mid-or high-grade heterogeneity respectively [Jin et al, 2009;Bedi et al, 2011;Jiang et al, 2012;Vyas et al, 2013]. Visual inspection of funnel plots were performed to ascertain publication bias [Begg and Mazumdar, 1994;Egger et al, 1997].…”

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“…According to fixed-effects model, SMR of lung cancer for TCDDexposed population was 1.12 (95%CI: 1.01-1.27) and significantly increased (Kogevinas et al, 1997;t Mannetje et al, 2005;McBride et al, 2009;Jiang et al, 2012). When focused on the latency of CPsR exposure (Fingerhut et al, 1991;Becher et al, 1996;Ramlow et al, 1996;McBride et al, 2009) and lung cancer diagnosis, SMR for over 20 years latency was 1.38 (95%CI; 1.06-1.78; p=0.01) where as other groups represent any increased risk for lung cancer.…”

rs965513 polymorphism as a common risk marker is associated with papillary thyroid cancer

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“…Begg's and Egger's tests were used to evaluate the asymmetry of the funnel plot [40]. It is assumed that in the absence of publication bias, the largest study will be plotted near the average, and smaller studies will be spread evenly on both sides of the average, creating a roughly funne-shaped distribution.…”