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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.
Afiliação
  • Kiryluk K; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA. kk473@columbia.edu.
  • Sanchez-Rodriguez E; Institute for Genomic Medicine, Columbia University, New York City, NY, USA. kk473@columbia.edu.
  • Zhou XJ; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Zanoni F; Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
  • Liu L; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Mladkova N; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Khan A; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Marasa M; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Zhang JY; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Balderes O; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Sanna-Cherchi S; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Bomback AS; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Canetta PA; Institute for Genomic Medicine, Columbia University, New York City, NY, USA.
  • Appel GB; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Radhakrishnan J; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Trimarchi H; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Sprangers B; Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
  • Cattran DC; Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.
  • Reich H; Department of Microbiology and Immunology, Laboratory of Molecular Immunology, KU Leuven, Leuven, Belgium.
  • Pei Y; Division of Nephrology, University Hospitals Leuven, Leuven, Belgium.
  • Ravani P; Department of Nephrology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
  • Galesic K; Department of Nephrology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
  • Maixnerova D; Department of Nephrology, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada.
  • Tesar V; Division of Nephrology, Department of Internal Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Stengel B; Zagreb Medical School, Zagreb, Croatia.
  • Metzger M; 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
  • Canaud G; 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
  • Maillard N; Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Versailles Saint Quentin University, INSERM Clinical Epidemiology Team, Villejuif, France.
  • Berthoux F; Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Versailles Saint Quentin University, INSERM Clinical Epidemiology Team, Villejuif, France.
  • Berthelot L; Université de Paris, Hôpital Necker-Enfants Malades, Paris, France.
  • Pillebout E; Nephrology, Dialysis, and Renal Transplantation Department, University North Hospital, Saint Etienne, France.
  • Monteiro R; Nephrology, Dialysis, and Renal Transplantation Department, University North Hospital, Saint Etienne, France.
  • Nelson R; CRTI, Nantes University, Nantes, France.
  • Wyatt RJ; Center for Research on Inflammation, University of Paris, INSERM and CNRS, Paris, France.
  • Smoyer W; Center for Research on Inflammation, University of Paris, INSERM and CNRS, Paris, France.
  • Mahan J; Division of Pediatric Nephrology, Department of Pediatrics, University of Utah, Salt Lake City, UT, USA.
  • Samhar AA; Division of Pediatric Nephrology, University of Tennessee Health Sciences Center, Memphis, TN, USA.
  • Hidalgo G; Children's Foundation Research Center, Le Bonheur Children's Hospital, Memphis, TN, USA.
  • Quiroga A; Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, OH, USA.
  • Weng P; Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, OH, USA.
  • Sreedharan R; Division of Pediatric Nephrology, Driscoll Children's Hospital, Corpus Christi, TX, USA.
  • Selewski D; Division of Pediatric Nephrology, Department of Pediatrics, HMH Hackensack University Medical Center, Hackensack, NJ, USA.
  • Davis K; Division of Pediatric Nephrology, Helen DeVos Children's Hospital, Grand Rapids, MI, USA.
  • Kallash M; Division of Pediatric Nephrology, Mattel Children's Hospital, Los Angeles, CA, USA.
  • Vasylyeva TL; Division of Pediatric Nephrology, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Rheault M; Division of Pediatric Nephrology, Mott Children's Hospital, Ann Arbor, MI, USA.
  • Chishti A; Division of Pediatric Nephrology, Department of Pediatrics, The Medical University of South Carolina (MUSC), Charleston, SC, USA.
  • Ranch D; Division of Pediatric Nephrology, SUNY Buffalo, Buffalo, NY, USA.
  • Wenderfer SE; Division of Pediatric Nephrology, Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, USA.
  • Samsonov D; Division of Pediatric Nephrology, University of Minnesota, Minneapolis, MN, USA.
Nat Genet ; 55(7): 1091-1105, 2023 07.
Article em En | MEDLINE | ID: mdl-37337107
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glomerulonefrite por IGA Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glomerulonefrite por IGA Tipo de estudo: Diagnostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos