Two independent alleles at 6q23 associated with risk of rheumatoid arthritis
Two independent alleles at 6q23 associated with risk of rheumatoid arthritis
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DOI：
10.1038/ng.2007.27
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发表时间：
2007-12-01
期刊：
影响因子：
30.8
通讯作者：
Altshuler, David
中科院分区：
文献类型：
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作者：
Plenge, Robert M.;Cotsapas, Chris;Altshuler, David
为了确定与类风湿性关节炎相关的易感性等位基因，我们对 397 名类风湿性关节炎患者的 116,204 个 SNP 进行了基因分型，并与来自弗雷明汉心脏研究 (1) 的 1,211 名相关个体的公开基因型数据进行了关联分析。在评估和调整技术和群体偏差后，我们在 6q23 处发现了一个 SNP（rs10499194，类似于 TNFAIP3 和 OLIG3 的 150 kb），在全基因组关联 (GWA) 扫描和 5,541 个其他病例对照样本中，该 SNP 与类风湿性关节炎可重复相关（P = 10(-3)，GWA 扫描；P < 10(-6)，复制； P = 10(-9)，合并）。在一项同时进行的研究中，Wellcome Trust 病例控制联盟 (WTCCC) 报告称，类风湿性关节炎易感性与位于 rs10499194 3.8 kb 处的不同 SNP（rs6920220；WTCCC 中 P = 5 x 10(-6)）(2) 密切相关。我们证明这两个 SNP 关联在统计上是独立的，在我们的数据和 WTCCC 数据的比较中各自可重复，并定义了 6q23 处类风湿性关节炎的风险和保护性单倍型。
To identify susceptibility alleles associated with rheumatoid arthritis, we genotyped 397 individuals with rheumatoid arthritis for 116,204 SNPs and carried out an association analysis in comparison to publicly available genotype data for 1,211 related individuals from the Framingham Heart Study(1). After evaluating and adjusting for technical and population biases, we identified a SNP at 6q23 ( rs10499194, similar to 150 kb from TNFAIP3 and OLIG3) that was reproducibly associated with rheumatoid arthritis both in the genome-wide association ( GWA) scan and in 5,541 additional case-control samples (P = 10(-3), GWA scan; P < 10(-6), replication; P = 10(-9), combined). In a concurrent study, the Wellcome Trust Case Control Consortium ( WTCCC) has reported strong association of rheumatoid arthritis susceptibility to a different SNP located 3.8 kb from rs10499194 ( rs6920220; P = 5 x 10(-6) in WTCCC)(2). We show that these two SNP associations are statistically independent, are each reproducible in the comparison of our data and WTCCC data, and define risk and protective haplotypes for rheumatoid arthritis at 6q23.