High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.
High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci.
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DOI：
10.1136/annrheumdis-2013-204749
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发表时间：
2015-03
影响因子：
27.4
通讯作者：
Bae SC
中科院分区：
文献类型：
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作者：
Kim K;Bang SY;Lee HS;Cho SK;Choi CB;Sung YK;Kim TH;Jun JB;Yoo DH;Kang YM;Kim SK;Suh CH;Shim SC;Lee SS;Lee J;Chung WT;Choe JY;Shin HD;Lee JY;Han BG;Nath SK;Eyre S;Bowes J;Pappas DA;Kremer JM;Gonzalez-Gay MA;Rodriguez-Rodriguez L;Ärlestig L;Okada Y;Diogo D;Liao KP;Karlson EW;Raychaudhuri S;Rantapää-Dahlqvist S;Martin J;Klareskog L;Padyukov L;Gregersen PK;Worthington J;Greenberg JD;Plenge RM;Bae SC
在类风湿关节炎的遗传学研究中，已经很好地阐明了一个高度多基因的病因学和祖先之间高度的等位基因共享。最近，免疫疾病位点的高密度基因分型阵列免疫芯片在欧洲血统的个体中确定了14个新的类风湿性关节炎风险位点。在这里，我们的目的是确定新的类风湿性关节炎的风险位点，使用韩国特定的免疫芯片数据。我们使用免疫芯片和GWAS阵列分析韩国类风湿性关节炎病例对照样本，用抗瓜氨酸肽抗体寻找类风湿性关节炎的新风险等位基因。为了提高功效，我们对韩国数据与先前发表的欧洲免疫芯片和GWAS数据进行了荟萃分析，总样本量为9，299例韩国和45，790例欧洲病例对照样本。我们确定了8个新的类风湿关节炎易感基因座（TNFSF 4、LBH、EOMES、ETS1-FLI1、COG6、RAD 51 B、UBASH3A和SYNGR 1），这些基因座通过了全基因组显著性阈值（p <5 × 10 − 8），并有证据表明1q25/TNFSF 4存在三个独立的风险等位基因。从7个新的基因座的风险等位基因，除了TNFSF 4基因座（单态的韩国人），与风险等位基因从以前建立的RA风险基因座，表现出很高的相关性的影响大小之间的祖先。此外，我们通过对密集基因分型的SNP进行跨种族比较，对代表潜在因果变异的SNP数量进行了细化。这项研究表明，密集定位和跨祖先分析的优势，确定潜在的因果SNP。此外，我们的研究结果支持了T细胞在发病机制中的重要性，以及各种自身免疫性疾病中风险位点频繁重叠的事实。
A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
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影响因子：
--
作者：
Freudenberg, Jan;Lee, Hye-Soon;Bae, Sang-Cheol
通讯作者：
Bae, Sang-Cheol
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
30.8
作者：
通讯作者：
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中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
影响因子：
30.8
作者：
Orr N;Lemnrau A;Cooke R;Fletcher O;Tomczyk K;Jones M;Johnson N;Lord CJ;Mitsopoulos C;Zvelebil M;McDade SS;Buck G;Blancher C;KConFab Consortium;Trainer AH;James PA;Bojesen SE;Bokmand S;Nevanlinna H;Mattson J;Friedman E;Laitman Y;Palli D;Masala G;Zanna I;Ottini L;Giannini G;Hollestelle A;Ouweland AM;Novaković S;Krajc M;Gago-Dominguez M;Castelao JE;Olsson H;Hedenfalk I;Easton DF;Pharoah PD;Dunning AM;Bishop DT;Neuhausen SL;Steele L;Houlston RS;Garcia-Closas M;Ashworth A;Swerdlow AJ
通讯作者：
Swerdlow AJ