Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.
Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.
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DOI：
10.1093/hmg/ddn128
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发表时间：
2008-08-01
影响因子：
3.5
通讯作者：
Worthington J
中科院分区：
文献类型：
--
作者：
Barton A;Thomson W;Ke X;Eyre S;Hinks A;Bowes J;Gibbons L;Plant D;Wellcome Trust Case Control Consortium;Wilson AG;Marinou I;Morgan A;Emery P;YEAR consortium;Steer S;Hocking L;Reid DM;Wordsworth P;Harrison P;Worthington J
类风湿性关节炎(RA)是一种典型的、常见的、复杂的自身免疫性疾病，与疾病病因学的遗传和环境因素有关。最近的全基因组和候选基因关联研究报告了两个新的RA易感基因。因此，我们使用惠康信托病例控制联盟(WTCCC)的输入数据调查了STAT4和TRAF1/C5基因座与类风湿关节炎关联的证据。在1860例RA病例和2930例对照样本中，没有发现与TRAF1/C5基因映射的变异相关的证据。映射到STAT4基因的变异确实显示出关联的证据(rs7574865，P=0.04)。鉴于TRAF1/C5基因座在之前两个来自欧洲血统人群的大型病例对照序列中的关联，以及WTCCC研究中STAT4基因座关联的证据，在一个独立的UK序列中测试了映射到这些基因座的单核苷酸多态与类风湿性关节炎的关联，该序列包含来自3000名疾病患者和3000名对照的DNA，并进行了包括WTCCC数据的联合分析。我们确认了STAT4和TRAF1/C5基因座与RA的关联，从而使已确认的易感基因座的数量达到5个。效应大小比以前报道的要小，但考虑到当前研究中调查的队列规模较大，可能会更准确地反映真实的效应大小。
Rheumatoid arthritis (RA) is an archetypal, common, complex autoimmune disease with both genetic and environmental contributions to disease aetiology. Two novel RA susceptibility loci have been reported from recent genome-wide and candidate gene association studies. We, therefore, investigated the evidence for association of the STAT4 and TRAF1/C5 loci with RA using imputed data from the Wellcome Trust Case Control Consortium (WTCCC). No evidence for association of variants mapping to the TRAF1/C5 gene was detected in the 1860 RA cases and 2930 control samples tested in that study. Variants mapping to the STAT4 gene did show evidence for association (rs7574865, P = 0.04). Given the association of the TRAF1/C5 locus in two previous large case–control series from populations of European descent and the evidence for association of the STAT4 locus in the WTCCC study, single nucleotide polymorphisms mapping to these loci were tested for association with RA in an independent UK series comprising DNA from >3000 cases with disease and >3000 controls and a combined analysis including the WTCCC data was undertaken. We confirm association of the STAT4 and the TRAF1/C5 loci with RA bringing to 5 the number of confirmed susceptibility loci. The effect sizes are less than those reported previously but are likely to be a more accurate reflection of the true effect size given the larger size of the cohort investigated in the current study.
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作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
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