| Autor: |
Dmitry Samsonov, Edyta Machura, Dita Maixnerova, Bénédicte Stengel, Domenico Santoro, Loreto Gesualdo, Silvana Savoldi, Raoul D. Nelson, Florian Kronenberg, Hajeong Lee, Licia Peruzzi, Gianluca Caridi, Magdalena Krajewska, Vladimir Tesar, Richard P. Lifton, William E. Smoyer, Erica Salvi, Marcin Zaniew, Magdalena Durlik, Guillaume Canaud, Heather N. Reich, Luisa Bono, Anna Köttgen, Pietro A. Canetta, Maurizio Garozzo, Marco Galliani, Bertrand Fontaine, Thomas Rauen, Renzo Mignani, Maria Szczepańska, Carmelita Marcantoni, Lili Liu, Pietro Ravani, Andrea Magnano, Aftab S. Chishti, Ulf Panzer, Dong Ki Kim, T Baczkowska, Ben Sprangers, Lucia Del Vecchio, Dorota Drozdz, Larisa Prikhodina, John B. Harley, Tomasz Liberek, Monika Pawlak-Bratkowska, Maria Stangou, Ichiei Narita, José Ballarín, Hernán Trimarchi, Barbara Moszczuk, Agnieszka Perkowska-Ptasińska, Maurizio Salvadori, Laureline Berthelot, Francesca Lugani, Katarzyna Siniewicz-Luzeńczyk, Claudia Izzi, Peter K. Gregersen, Isabella Pisani, Michelle N. Rheault, Adele Mitrotti, Ruth J. F. Loos, Xu-jie Zhou, Krzysztof Pawlaczyk, Kai-Uwe Eckardt, Giovanni Frasca, Piergiorgio Messa, Elisabet Ars, Antonio Amoroso, Evangeline Pillebout, Vito Annese, Kresimir Galesic, Tibor Kovács, Hitoshi Suzuki, Krzysztof Kiryluk, Nan Chen, Guido Gembillo, Olivia Balderes, Ciro Esposito, Małgorzata Mizerska-Wasiak, Daniel P. Gale, Sreeja Parameswaran, Michał Florczak, Jai Radhakrishnan, Alicja Dbska-Slizien, Ireneusz Habura, Matthew T. Weirauch, Belong Cho, Guillermo Hidalgo, John D. Mahan, Bruce A. Julian, Andre Franke, Alejandro Quiroga, Rosanna Coppo, Atlas Khan, Murim Choi, Giuliano Boscutti, Izabella Kuzmiuk-Glembin, Nicolas Maillard, Rosaria Polci, Jonathan Barratt, Dario Roccatello, Donna J. Claes, Marie Metzger, Chris Cotsapas, Yasar Caliskan, Raji Sreedharan, Judit Nagy, Francesca Zanoni, Monica Bodria, Dariusz Runowski, Hong Zhang, Magorzata Panczyk-Tomaszewska, Robert J. Wyatt, Claudio Ponticelli, Nikol Mladkova, Przemysław Sikora, Marcin Tkaczyk, Riccardo Magistroni, Gerald B. Appel, Ans van Wijk, Krzysztof Mucha, Barbara Bułło-Piontecka, Jan Novak, Giovanni-Giorgio Battaglia, Anna Materna-Kiryluk, Emanuela Boer, Francesco Scolari, David A. van Heel, Tomasz Hryszko, Keefe Davis, Thilini Abeygunaratne, Simone Sanna-Cherchi, Zbigniew Heleniak, Eimear E. Kenny, Sigrid Lundberg, Al-Akash Samhar, Francesco Londrino, Tetyana L. Vasylyeva, Scott E. Wenderfer, Federico Alberici, Yon Su Kim, Enrico Fiaccadori, Bruno Vogt, Gianluigi Zaza, Stanisaw Niemczyk, Patricia L. Weng, Donatella Spotti, Gian Marco Ghiggeri, Dimitrios Goumenos, Daniel Ranch, David T. Selewski, Monika Miklaszewska, Laila-Yasmin Mani, Jin-Ho Park, Jürgen Floege, Antonello Pani, Renato C. Monteiro, Leszek Paczek, Akchurin Oleh, Maddalena Marasa, Ana Huerta, Sandro Feriozzi, Simona Granata, Andrew S. Bomback, Pascal Schlosser, York Pei, Vittoria Esposito, Mahmoud Kallash, Pasquale Zamboli, Cisca Wijmenga, Daniele Cusi, Elena Sanchez-Rodriguez, Ali G. Gharavi, Francois Berthoux, Shin Goto, Natalia Krata, Leah C. Kottyan, Norbert Kwella, Iuliana Ionita-Laza, Daniel C. Cattran, Cristina Barlassina, Arif B. Ekici, Katarzyna Dyga, Philip A. Kalra, Dorota Kamińska, Jingyuan Xie, Elisa Delbarba, Jun-Ying Zhang |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.19.21265383 |
| Popis: |
IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. We performed a genome-wide association study involving 10,146 kidney biopsy-diagnosed IgAN cases and 28,751 matched controls across 17 international cohorts. We defined 30 independent genome-wide significant risk loci jointly explaining 11% of disease risk. A total of 16 loci were novel, including TNFSF4, REL, CD28, CXCL8/PF4V1, LY86, LYN, ANXA3, TNFSF8/15, REEP3, ZMIZ1, RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The SNP-based heritability of IgAN was estimated at 23%. We observed a positive genetic correlation between IgAN and total serum IgA levels, allergy, tonsillectomy, and several infections, and a negative correlation with inflammatory bowel disease. All significant non-HLA loci shared with serum IgA levels had a concordant effect on the risk of IgAN. Moreover, IgAN loci were globally enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. The explained heritability was enriched in the regulatory elements of cells from the immune and hematopoietic systems and intestinal mucosa, providing support for the pathogenic role of extra-renal tissues. The polygenic risk of IgAN was associated with early disease onset, increased lifetime risk of kidney failure, as well as hematuria and several other traits in a phenome-wide association study of 590,515 individuals. In the comprehensive functional annotation analysis of candidate causal genes across genome-wide significant loci, we observed the convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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