Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens.
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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。
DOI：
10.1038/ng.3118
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发表时间：
2014-11
期刊：
影响因子：
30.8
通讯作者：
Gharavi, Ali G.
中科院分区：
文献类型：
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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.
我们进行了伊加肾病（IgAN）的全基因组关联研究（GWAS），这是肾小球肾炎的最常见形式，在20，612名欧洲和东亚血统的个体中发现并随访。我们确定了六个新的全基因组显著关联，其中四个在ITGAM-ITGAX，VAV 3和CARD 9中，两个新的独立信号在HLA-DQB 1和DEFA中。我们复制了先前报道的9个信号，包括HLA-DQB 1和DEFA基因座中已知的SNP。风险等位基因的累积负担与疾病发作时的年龄密切相关。大多数基因座与炎症性肠病（IBD）的风险直接相关，或与肠上皮屏障的维持和对粘膜病原体的反应直接相关。风险等位基因的地理空间分布是高度暗示的多位点适应和遗传风险与当地病原体的变化，特别是蠕虫的多样性，这表明宿主肠道病原体的相互作用在塑造IgAN的遗传景观的可能作用。
We performed a genome-wide association study (GWAS) of IgA nephropathy (IgAN), the most common form of glomerulonephritis, with discovery and follow-up in 20,612 individuals of European and East Asian ancestry. We identified six novel genome-wide significant associations, four in ITGAM-ITGAX, VAV3 and CARD9 and two new independent signals at HLA-DQB1 and DEFA. We replicated the nine previously reported signals, including known SNPs in the HLA-DQB1 and DEFA loci. The cumulative burden of risk alleles is strongly associated with age at disease onset. Most loci are either directly associated with risk of inflammatory bowel disease (IBD) or maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The geo-spatial distribution of risk alleles is highly suggestive of multi-locus adaptation and the genetic risk correlates strongly with variation in local pathogens, particularly helminth diversity, suggesting a possible role for host-intestinal pathogen interactions in shaping the genetic landscape of IgAN.
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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：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
影响因子：
15.3
作者：
Fujikawa, K;Miletic, AV;Alt, FW;Faccio, R;Brown, T;Hoog, J;Fredericks, J;Nishi, S;Mildiner, S;Moores, SL;Brugge, J;Rosen, FS;Swat, W
通讯作者：
Swat, W
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：
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.