Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
Standard
Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy. / 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.
In: NAT GENET, Vol. 55, No. 7, 07.2023, p. 1091-1105.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Genome-wide association analyses define pathogenic signaling pathways and prioritize drug targets for IgA nephropathy
AU - Kiryluk, Krzysztof
AU - Sanchez-Rodriguez, Elena
AU - Zhou, Xu-Jie
AU - Zanoni, Francesca
AU - Liu, Lili
AU - Mladkova, Nikol
AU - Khan, Atlas
AU - Marasa, Maddalena
AU - Zhang, Jun Y
AU - Balderes, Olivia
AU - Sanna-Cherchi, Simone
AU - Bomback, Andrew S
AU - Canetta, Pietro A
AU - Appel, Gerald B
AU - Radhakrishnan, Jai
AU - Trimarchi, Hernan
AU - Sprangers, Ben
AU - Cattran, Daniel C
AU - Reich, Heather
AU - Pei, York
AU - Ravani, Pietro
AU - Galesic, Kresimir
AU - Maixnerova, Dita
AU - Tesar, Vladimir
AU - Stengel, Benedicte
AU - Metzger, Marie
AU - Canaud, Guillaume
AU - Maillard, Nicolas
AU - Berthoux, Francois
AU - Berthelot, Laureline
AU - Pillebout, Evangeline
AU - Monteiro, Renato
AU - Nelson, Raoul
AU - Wyatt, Robert J
AU - Smoyer, William
AU - Mahan, John
AU - Samhar, Al-Akash
AU - Hidalgo, Guillermo
AU - Quiroga, Alejandro
AU - Weng, Patricia
AU - Sreedharan, Raji
AU - Selewski, David
AU - Davis, Keefe
AU - Kallash, Mahmoud
AU - Vasylyeva, Tetyana L
AU - Rheault, Michelle
AU - Chishti, Aftab
AU - Ranch, Daniel
AU - Wenderfer, Scott E
AU - Samsonov, Dmitry
AU - Claes, Donna J
AU - Akchurin, Oleh
AU - Goumenos, Dimitrios
AU - Stangou, Maria
AU - Nagy, Judit
AU - Kovacs, Tibor
AU - Fiaccadori, Enrico
AU - Amoroso, Antonio
AU - Barlassina, Cristina
AU - Cusi, Daniele
AU - Del Vecchio, Lucia
AU - Battaglia, Giovanni Giorgio
AU - Bodria, Monica
AU - Boer, Emanuela
AU - Bono, Luisa
AU - Boscutti, Giuliano
AU - Caridi, Gianluca
AU - Lugani, Francesca
AU - Ghiggeri, GianMarco
AU - Coppo, Rosanna
AU - Peruzzi, Licia
AU - Esposito, Vittoria
AU - Esposito, Ciro
AU - Feriozzi, Sandro
AU - Polci, Rosaria
AU - Frasca, Giovanni
AU - Galliani, Marco
AU - Garozzo, Maurizio
AU - Mitrotti, Adele
AU - Gesualdo, Loreto
AU - Granata, Simona
AU - Zaza, Gianluigi
AU - Londrino, Francesco
AU - Magistroni, Riccardo
AU - Pisani, Isabella
AU - Magnano, Andrea
AU - Marcantoni, Carmelita
AU - Messa, Piergiorgio
AU - Mignani, Renzo
AU - Pani, Antonello
AU - Ponticelli, Claudio
AU - Roccatello, Dario
AU - Salvadori, Maurizio
AU - Salvi, Erica
AU - Santoro, Domenico
AU - Gembillo, Guido
AU - Savoldi, Silvana
AU - Spotti, Donatella
AU - Zamboli, Pasquale
AU - Izzi, Claudia
AU - Alberici, Federico
AU - Delbarba, Elisa
AU - Florczak, Michał
AU - Krata, Natalia
AU - Mucha, Krzysztof
AU - Pączek, Leszek
AU - Niemczyk, Stanisław
AU - Moszczuk, Barbara
AU - Pańczyk-Tomaszewska, Malgorzata
AU - Mizerska-Wasiak, Malgorzata
AU - Perkowska-Ptasińska, Agnieszka
AU - Bączkowska, Teresa
AU - Durlik, Magdalena
AU - Pawlaczyk, Krzysztof
AU - Sikora, Przemyslaw
AU - Zaniew, Marcin
AU - Kaminska, Dorota
AU - Krajewska, Magdalena
AU - Kuzmiuk-Glembin, Izabella
AU - Heleniak, Zbigniew
AU - Bullo-Piontecka, Barbara
AU - Liberek, Tomasz
AU - Dębska-Slizien, Alicja
AU - Hryszko, Tomasz
AU - Materna-Kiryluk, Anna
AU - Miklaszewska, Monika
AU - Szczepańska, Maria
AU - Dyga, Katarzyna
AU - Machura, Edyta
AU - Siniewicz-Luzeńczyk, Katarzyna
AU - Pawlak-Bratkowska, Monika
AU - Tkaczyk, Marcin
AU - Runowski, Dariusz
AU - Kwella, Norbert
AU - Drożdż, Dorota
AU - Habura, Ireneusz
AU - Kronenberg, Florian
AU - Prikhodina, Larisa
AU - van Heel, David
AU - Fontaine, Bertrand
AU - Cotsapas, Chris
AU - Wijmenga, Cisca
AU - Franke, Andre
AU - Annese, Vito
AU - Gregersen, Peter K
AU - Parameswaran, Sreeja
AU - Weirauch, Matthew
AU - Kottyan, Leah
AU - Harley, John B
AU - Suzuki, Hitoshi
AU - Narita, Ichiei
AU - Goto, Shin
AU - Lee, Hajeong
AU - Kim, Dong Ki
AU - Kim, Yon Su
AU - Park, Jin-Ho
AU - Cho, BeLong
AU - Choi, Murim
AU - Van Wijk, Ans
AU - Huerta, Ana
AU - Ars, Elisabet
AU - Ballarin, Jose
AU - Lundberg, Sigrid
AU - Vogt, Bruno
AU - Mani, Laila-Yasmin
AU - Caliskan, Yasar
AU - Barratt, Jonathan
AU - Abeygunaratne, Thilini
AU - Kalra, Philip A
AU - Gale, Daniel P
AU - Panzer, Ulf
AU - Rauen, Thomas
AU - Floege, Jürgen
AU - Schlosser, Pascal
AU - Ekici, Arif B
AU - Eckardt, Kai-Uwe
AU - Chen, Nan
AU - Xie, Jingyuan
AU - Lifton, Richard P
AU - Loos, Ruth J F
AU - Kenny, Eimear E
AU - Ionita-Laza, Iuliana
AU - Köttgen, Anna
AU - Julian, Bruce A
AU - Novak, Jan
AU - Scolari, Francesco
AU - Zhang, Hong
AU - Gharavi, Ali G
N1 - © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
KW - Animals
KW - Mice
KW - Glomerulonephritis, IGA/drug therapy
KW - Genome-Wide Association Study
KW - Immunoglobulin A/genetics
U2 - 10.1038/s41588-023-01422-x
DO - 10.1038/s41588-023-01422-x
M3 - SCORING: Journal article
C2 - 37337107
VL - 55
SP - 1091
EP - 1105
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 7
ER -