title: Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied in the past two decades.
abstract: OBJECTIVE
  Candidate 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.
  
  
  METHODS
  Two 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Yongshuai
authors.initials: Y
authors.lastname: Jiang
authors.forename: Ruijie
authors.initials: R
authors.lastname: Zhang
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zheng
authors.forename: Panpan
authors.initials: P
authors.lastname: Liu
authors.forename: Guoping
authors.initials: G
authors.lastname: Tang
authors.forename: Hongchao
authors.initials: H
authors.lastname: Lv
authors.forename: Lanying
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Shang
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Zhan
authors.forename: Wenhua
authors.initials: W
authors.lastname: Lv
authors.forename: Miao
authors.initials: M
authors.lastname: Shi
authors.forename: Ruimin
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*