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荟萃分析确定了日本人群中与类风湿关节炎相关的九个新位点。

Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.

机构信息

Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Yokohama, Japan.

出版信息

Nat Genet. 2012 Mar 25;44(5):511-6. doi: 10.1038/ng.2231.

Abstract

Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves' disease (P = 3.5 × 10(-4) and 2.9 × 10(-4), respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.

摘要

类风湿关节炎是一种常见的自身免疫性疾病,其特征为慢性炎症。我们报告了一项在日本人群中进行的全基因组关联研究(GWAS)的荟萃分析,该研究包括 4074 名类风湿关节炎患者(病例)和 16891 名对照者,随后在 5277 名类风湿关节炎患者和 21684 名对照者中进行了复制。我们的研究在 P < 5.0 × 10(-8)的阈值下确定了九个与类风湿关节炎新相关的位点,包括 B3GNT2、ANXA3、CSF2、CD83、NFKBIE、ARID5B、PDE2A-ARAP1、PLD4 和 PTPN2。ANXA3 也与系统性红斑狼疮易感性相关(P = 0.0040),B3GNT2 和 ARID5B 与格雷夫斯病相关(P = 3.5 × 10(-4)和 2.9 × 10(-4))。我们进行了一项与先前在欧洲血统个体中进行的荟萃分析的多血统比较分析(5539 名类风湿关节炎患者和 20169 名对照者)。这为人群之间存在共同的类风湿关节炎遗传风险提供了证据。

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