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Title: Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
Authors: Kiryluk, K.
Li, Y.
Scolari, F.
Sanna-Cherchi, S.
Choi, M.
Verbitsky, M.
Fasel, D.
Lata, S.
Prakash, S.
Shapiro, S.
Fischman, C.
Snyder, H. J.
Appel, G.
Izzi, C.
Viola, B. F.
Dallera, N.
Del Vecchio, L.
Barlassina, C.
Salvi, E.
Bertinetto, F. E.
Amoroso, A.
Savoldi, S.
Rocchietti, M.
Amore, A.
Peruzzi, L.
Coppo, R.
Salvadori, M.
Ravani, P.
Magistroni, R.
Ghiggeri, G. M.
Caridi, G.
Bodria, M.
Lugani, F.
Allegri, L.
Delsante, M.
Maiorana, M.
Magnano, A.
Frasca, G.
Boer, E.
Boscutti, G.
Ponticelli, C.
Mignani, R.
Marcantoni, C.
Di Landro, D.
Santoro, D.
Pani, A.
Polci, R.
Feriozzi, S.
Chicca, S.
Galliani, M.
Gigante, M.
Gesualdo, L.
Zamboli, P.
Battaglia, G. G.
Garozzo, M.
Maixnerová, D.
Tesar, V.
Eitner, F.
Rauen, T.
Floege, J.
Kovacs, T.
Nagy, J.
Mucha, K.
Pączek, L.
Zaniew, M.
Mizerska-Wasiak, M.
Roszkowska-Blaim, M.
Pawlaczyk, K.
Gale, D.
Barratt, Jonathan
Thibaudin, L.
Berthoux, F.
Canaud, G.
Boland, A.
Metzger, M.
Panzer, U.
Suzuki, H.
Goto, S.
Narita, I.
Caliskan, Y.
Xie, J.
Hou, P.
Chen, N.
Zhang, H.
Wyatt, R. J.
Novak, J.
Julian, B. A.
Feehally, John
Stengel, B.
Cusi, D.
Lifton, R. P.
Gharavi, A. G.
First Published: 12-Oct-2014
Publisher: Nature Publishing Group
Citation: Nature Genetics, 2014, 46 (11), pp. 1187-1196
Abstract: 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.
DOI Link: 10.1038/ng.3118
ISSN: 1061-4036
eISSN: 1546-1718
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2014, Rights Managed by Nature Publishing Group.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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