Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.
Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.
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欧洲和亚洲人群基于基因的全基因组关联分析确定了类风湿关节炎的新基因
DOI：
10.1371/journal.pone.0167212
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lei SF
中科院分区：
文献类型：
--
作者：
Zhu H;Xia W;Mo XB;Lin X;Qiu YH;Yi NJ;Zhang YH;Deng FY;Lei SF
目的类风湿性关节炎（RA）是一种复杂的自身免疫性疾病。使用基于基因的关联研究策略，本研究旨在检测未知的RA易感性，并解决欧洲和亚洲人群之间RA遗传易感性的种族差异。方法采用KGG 2.5软件对公开的大型RA数据集（欧洲受试者14,361例RA病例和43,923例对照，亚洲受试者4,873例RA病例和17,642例对照）进行基于基因的关联分析。对于新鉴定的RA相关基因，分别用大卫和STRING版本10.0进行基因集富集分析和蛋白质-蛋白质相互作用分析。使用4个GEO数据集进行差异表达验证。在我们的内部RA病例和对照组中，通过ELISA测量了三个选定的“高度验证”基因的表达水平。结果共发现RA相关基因221个，其中重叠基因71个，欧洲特异基因76个，亚洲特异基因74个。其中105个基因在RA患者和健康对照组之间至少在一个数据集中有显著差异表达，尤其是20个基因，其中11个基因“重叠”（ABCF 1，FLOT 1，HLA-F，IER 3，TUBB，ZKSCAN 4，BTN 3A 3，HSP 90 AB 1，CUTA，BRD 2，HLA-DMA），5“欧洲特异性”（PHTF 1、RPS 18、BAK 1、TNFRSF 14、SUOX）和4个“亚洲特异性”基因（RNASET 2、HFE、BTN 2A 2、MAPK 13），其差异表达至少在三个数据集中是显著的。两个选定的基因FLOT 1（P值= 1.70E-02）和HLA-DMA（P值= 4.70E-02）在血浆中的蛋白表达在我们的内部样本中有显著差异。结论本研究共发现221个RA相关新基因，其中20个候选基因在RA发病中具有重要意义。结果解决了种族遗传背景差异的RA易感性之间的欧洲和亚洲人群，并检测到一长串的重叠或种族特异性RA基因。该研究不仅大大增加了我们对RA遗传易感性的了解，而且还为两个种族中RA的民族遗传同质性和异质性提供了重要见解。
Objective Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Methods Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected ‘highly verified’ genes were measured by ELISA among our in-house RA cases and controls. Results A total of 221 RA-associated genes were newly identified by gene-based association study, including 71‘overlapped’, 76 ‘European-specific’ and 74 ‘Asian-specific’ genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 ‘overlapped’ (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 ‘European-specific’ (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 ‘Asian-specific’ (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Conclusion Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The study not only greatly increases our understanding of genetic susceptibility to RA, but also provides important insights into the ethno-genetic homogeneity and heterogeneity of RA in both ethnicities.
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作者：
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影响因子：
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影响因子：
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