Identification of new susceptibility loci for IgA nephropathy in Han Chinese.
Identification of new susceptibility loci for IgA nephropathy in Han Chinese.
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汉族IgA肾病新易感位点的鉴定
DOI：
10.1038/ncomms8270
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发表时间：
2015-06-01
影响因子：
16.6
通讯作者：
Liu, Jian-Jun
中科院分区：
文献类型：
--
作者：
Li, Ming;Foo, Jia-Nee;Wang, Jin-Quan;Low, Hui-Qi;Tang, Xue-Qing;Toh, Kai-Yee;Yin, Pei-Ran;Khor, Chiea-Chuen;Goh, Yu-Fen;Irwan, Ishak D.;Xu, Ri-Cong;Andiappan, Anand K.;Bei, Jin-Xin;Rotzschke, Olaf;Chen, Meng-Hua;Cheng, Ching-Yu;Sun, Liang-Dan;Jiang, Geng-Ru;Wong, Tien-Yin;Lin, Hong-Li;Aung, Tin;Liao, Yun-Hua;Saw, Seang-Mei;Ye, Kun;Ebstein, Richard P.;Chen, Qin-Kai;Shi, Wei;Chew, Soo-Hong;Chen, Jian;Zhang, Fu-Ren;Li, Sheng-Ping;Xu, Gang;Tai, E. Shyong;Wang, Li;Chen, Nan;Zhang, Xue-Jun;Zeng, Yi-Xin;Zhang, Hong;Liu, Zhi-Hong;Yu, Xue-Qing;Liu, Jian-Jun
IgA肾病(IgAN)是最常见的原发性肾小球肾炎之一。以前发现的全基因组关联研究(GWAS)基因座只解释了疾病风险的一小部分。为了确定中国汉族人新的易感基因座，我们进行了包括8,313例病例和19,680名对照的四阶段遗传多样性分析。在这里，我们发现了位于3q27.3上的ST6GAL1(rs7634389，优势比(OR)=1.13，P=7.27×10−10)、ACCSon 11p11.2(rs2074038，OR=1.14，P=3.93×10−9)和8q22.3上的ODF1-KLF10(rs2033562，OR=1.13，P=1.41×10−9)的新关联，并验证了最近报道的ITGAX-ITGAMon 16p11.2(rs7190997，OR=1.22，P=2.26×10−19)上的三个独立信号(rs2738058，P=1.15×10−19；rs12716641，P=9.53×10−9；Rs9314614，P=4.25×10−9，多因素关联)。3q27.3和11p11.2的易感变异与血细胞中的mRNA表达水平密切相关，而ST6GAL1、ACCS和DEA的易感变异的等位基因频率与IgAN患病率的地理变异相关。我们的发现扩大了我们对IgAN遗传易感性的理解，并为研究IgAN的分子机制提供了新的生物学见解。
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations atST6GAL1on 3q27.3 (rs7634389, odds ratio (OR)=1.13,P=7.27 × 10−10),ACCSon 11p11.2 (rs2074038, OR=1.14,P=3.93 × 10−9) andODF1-KLF10on 8q22.3 (rs2033562, OR=1.13,P=1.41 × 10−9), validate a recently reported association atITGAX-ITGAMon 16p11.2 (rs7190997, OR=1.22,P=2.26 × 10−19), and identify three independent signals within theDEFAlocus (rs2738058,P=1.15 × 10−19; rs12716641,P=9.53 × 10−9; rs9314614,P=4.25 × 10−9, multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants withinST6GAL1,ACCSandDEFAcorrelate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
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IgA肾病的新风险基因座的发现暗示了与肠道病原体免疫有关的基因。
影响因子：
30.8
作者：
Kiryluk, Krzysztof;Li, Yifu;Scolari, Francesco;Sanna-Cherchi, Simone;Choi, Murim;Verbitsky, Miguel;Fasel, David;Lata, Sneh;Prakash, Sindhuri;Shapiro, Samantha;Fischman, Clara;Snyder, Holly J.;Appel, Gerald;Izzi, Claudia;Viola, Battista Fabio;Dallera, Nadia;Del Vecchio, Lucia;Barlassina, Cristina;Salvi, Erika;Bertinetto, Francesca Eleonora;Amoroso, Antonio;Savoldi, Silvana;Rocchietti, Marcella;Amore, Alessandro;Peruzzi, Licia;Coppo, Rosanna;Salvadori, Maurizio;Ravani, Pietro;Magistroni, Riccardo;Ghiggeri, Gian Marco;Caridi, Gianluca;Bodria, Monica;Lugani, Francesca;Allegri, Landino;Delsante, Marco;Maiorana, Mariarosa;Magnano, Andrea;Frasca, Giovanni;Boer, Emanuela;Boscutti, Giuliano;Ponticelli, Claudio;Mignani, Renzo;Marcantoni, Carmelita;Di Landro, Domenico;Santoro, Domenico;Pani, Antonello;Polci, Rosaria;Feriozzi, Sandro;Chicca, Silvana;Galliani, Marco;Gigante, Maddalena;Gesualdo, Loreto;Zamboli, Pasquale;Battaglia, Giovanni Giorgio;Garozzo, Maurizio;Maixnerova, Dita;Tesar, Vladimir;Eitner, Frank;Rauen, Thomas;Floege, Juergen;Kovacs, Tibor;Nagy, Judit;Mucha, Krzysztof;Paczek, Leszek;Zaniew, Marcin;Mizerska-Wasiak, Malgorzata;Roszkowska-Blaim, Maria;Pawlaczyk, Krzysztof;Gale, Daniel;Barratt, Jonathan;Thibaudin, Lise;Berthoux, Francois;Canaud, Guillaume;Boland, Anne;Metzger, Marie;Panzer, Ulf;Suzuki, Hitoshi;Goto, Shin;Narita, Ichiei;Caliskan, Yasar;Xie, Jingyuan;Hou, Ping;Chen, Nan;Zhang, Hong;Wyatt, Robert J.;Novak, Jan;Julian, Bruce A.;Feehally, John;Stengel, Benedicte;Cusi, Daniele;Lifton, Richard P.;Gharavi, Ali G.
通讯作者：
Gharavi, Ali G.
影响因子：
3.7
作者：
Jia X;Zha T;Wu B;Zhang Y;Chen W;Wang X;Yu H;He G
通讯作者：
He G
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.