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Nature genetics · 2023

Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy.

СтатьяПоддержка правительства СШАПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kiryluk Krzysztof, Sanchez-Rodriguez Elena, Zhou Xu-Jie, Zanoni Francesca, Liu Lili, Mladkova Nikol, Khan Atlas, Marasa Maddalena, Zhang Jun Y, Balderes Olivia, Sanna-Cherchi Simone, Bomback Andrew S, Canetta Pietro A, Appel Gerald B, Radhakrishnan Jai, Trimarchi Hernan, Sprangers Ben, Cattran Daniel C, Reich Heather, Pei York, Ravani Pietro, Galesic Kresimir, Maixnerova Dita, Tesar Vladimir, Stengel Benedicte, Metzger Marie, Canaud Guillaume, Maillard Nicolas, Berthoux Francois, Berthelot Laureline, Pillebout Evangeline, Monteiro Renato, Nelson Raoul, Wyatt Robert J, Smoyer William, Mahan John, Samhar Al-Akash, Hidalgo Guillermo, Quiroga Alejandro, Weng Patricia, Sreedharan Raji, Selewski David, Davis Keefe, Kallash Mahmoud, Vasylyeva Tetyana L, Rheault Michelle, Chishti Aftab, Ranch Daniel, Wenderfer Scott E, Samsonov Dmitry, Claes Donna J, Akchurin Oleh, Goumenos Dimitrios, Stangou Maria, Nagy Judit, Kovacs Tibor, Fiaccadori Enrico, Amoroso Antonio, Barlassina Cristina, Cusi Daniele, Del Vecchio Lucia, Battaglia Giovanni Giorgio, Bodria Monica, Boer Emanuela, Bono Luisa, Boscutti Giuliano, Caridi Gianluca, Lugani Francesca, Ghiggeri GianMarco, Coppo Rosanna, Peruzzi Licia, Esposito Vittoria, Esposito Ciro, Feriozzi Sandro, Polci Rosaria, Frasca Giovanni, Galliani Marco, Garozzo Maurizio, Mitrotti Adele, Gesualdo Loreto, Granata Simona, Zaza Gianluigi, Londrino Francesco, Magistroni Riccardo, Pisani Isabella, Magnano Andrea, Marcantoni Carmelita, Messa Piergiorgio, Mignani Renzo, Pani Antonello, Ponticelli Claudio, Roccatello Dario, Salvadori Maurizio, Salvi Erica, Santoro Domenico, Gembillo Guido, Savoldi Silvana, Spotti Donatella, Zamboli Pasquale, Izzi Claudia, Alberici Federico, Delbarba Elisa, Florczak Michał, Krata Natalia, Mucha Krzysztof, Pączek Leszek, Niemczyk Stanisław, Moszczuk Barbara, Pańczyk-Tomaszewska Malgorzata, Mizerska-Wasiak Malgorzata, Perkowska-Ptasińska Agnieszka, Bączkowska Teresa, Durlik Magdalena, Pawlaczyk Krzysztof, Sikora Przemyslaw, Zaniew Marcin, Kaminska Dorota, Krajewska Magdalena, Kuzmiuk-Glembin Izabella, Heleniak Zbigniew, Bullo-Piontecka Barbara, Liberek Tomasz, Dębska-Slizien Alicja, Hryszko Tomasz, Materna-Kiryluk Anna, Miklaszewska Monika, Szczepańska Maria, Dyga Katarzyna, Machura Edyta, Siniewicz-Luzeńczyk Katarzyna, Pawlak-Bratkowska Monika, Tkaczyk Marcin, Runowski Dariusz, Kwella Norbert, Drożdż Dorota, Habura Ireneusz, Kronenberg Florian, Prikhodina Larisa, van Heel David, Fontaine Bertrand, Cotsapas Chris, Wijmenga Cisca, Franke Andre, Annese Vito, Gregersen Peter K, Parameswaran Sreeja, Weirauch Matthew, Kottyan Leah, Harley John B, Suzuki Hitoshi, Narita Ichiei, Goto Shin, Lee Hajeong, Kim Dong Ki, Kim Yon Su, Park Jin-Ho, Cho BeLong, Choi Murim, Van Wijk Ans, Huerta Ana, Ars Elisabet, Ballarin Jose, Lundberg Sigrid, Vogt Bruno, Mani Laila-Yasmin, Caliskan Yasar, Barratt Jonathan, Abeygunaratne Thilini, Kalra Philip A, Gale Daniel P, Panzer Ulf, Rauen Thomas, Floege Jürgen, Schlosser Pascal, Ekici Arif B, Eckardt Kai-Uwe, Chen Nan, Xie Jingyuan, Lifton Richard P, Loos Ruth J F, Kenny Eimear E, Ionita-Laza Iuliana, Köttgen Anna, Julian Bruce A, Novak Jan, Scolari Francesco, Zhang Hong, Gharavi Ali G

Аннотация

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum IgA levels. High polygenic score for IgAN was associated with earlier onset of kidney failure. In a comprehensive functional annotation analysis of candidate causal genes, we observed convergence of biological candidates on a common set of inflammatory signaling pathways and cytokine ligand-receptor pairs, prioritizing potential new drug targets.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты