作者
Krzysztof Kiryluk,Yifu Li,Francesco Scolari,Simone Sanna‐Cherchi,Murim Choi,Miguel Verbitsky,David Fasel,Sneh Lata,Sindhuri Prakash,Stanley S. Shapiro,Clara Fischman,Holly J. Snyder,Gerald B. Appel,Claudia Izzi,Battista Fabio Viola,Nadia Dallera,Lucia Del Vecchio,Cristina Barlassina,Erika Salvi,Francesca Bertinetto,Antonio Amoroso,Silvana Savoldi,Marcella Rocchietti,Alessandro Amore,Licia Peruzzi,Rosanna Coppo,Maurizio Salvadori,Pietro Ravani,Riccardo Magistroni,Gian Marco Ghiggeri,Gianluca Caridi,Monica Bodria,Francesca Lugani,Landino Allegri,Marco Delsante,Mariarosa Maiorana,Andrea Magnano,Giovanni M. Frascà,Emanuela Boer,Giuliano Boscutti,Claudio Ponticelli,Renzo Mignani,Carmelita Marcantoni,Domenico Di Landro,Domenico Santoro,Antonello Pani,Rosaria Polci,Sandro Feriozzi,Silvana Chicca,Marco Galliani,Maddalena Gigante,Loreto Gesualdo,Pasquale Zamboli,Giovanni Giorgio Battaglia,Maurizio Garozzo,Dita Maixnerová,Vladimı́r Tesař,Frank Eitner,Thomas Rauen,Jürgen Floege,Tibor Kovács,Judit Nagy,Krzysztof Mucha,Leszek Pączek,Marcin Zaniew,Małgorzata Mizerska-Wasiak,Maria Roszkowska‐Blaim,Krzysztof Pawlaczyk,Daniel P. Gale,Jonathan Barratt,Lise Thibaudin,F Berthoux,Guillaume Canaud,Anne Boland,Marie Metzger,Ulf Panzer,Hitoshi Suzuki,Shin Goto,Ichiei Narita,Yaşar Çalışkan,Jingyuan Xie,Ping Hou,Nan Chen,Hong Zhang,Robert Wyatt,Jan Novák,Bruce A. Julian,John Feehally,Bénédicte Stengel,Daniele Cusi,Richard P. Lifton,Ali G. Gharavi
摘要
Ali Gharavi and colleagues report a genome-wide association analysis of IgA nephropathy in over 20,000 individuals of European and East Asian ancestry. They identify genome-wide significant signals at three new loci near VAV3, CARD9 and ITGAM-ITGAX and correlations between genetic risk and pathogen diversity. 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 new 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 geospatial distribution of risk alleles is highly suggestive of multi-locus adaptation, and 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.