Genome-wide association and functional follow-up reveals new loci for kidney function
journal contribution
posted on 2025-05-08, 15:37 authored by Cristian Pattaro, Anna Kottgen, Man Li, Andre G. Uitterlinden, Fernando Rivadeneira, Yurii S. Aulchenko, Ozren Polasek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Daniela Ruggiero, Sven Bergmann, Xiaoyi Gao, Mika Kahonen, Jorma Viikari, Tiit Nikopensius, Michael Province, Shamika Ketkar, Helen Colhoun, Alex Doney, Antonietta Robino, Franco Giulianini, Bernhard K. Kramer, Mathias Gorski, Laura Portas, Ian Ford, Brendan M. Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Marie Metzger, Paul Mitchell, Qiong Yang, Marina Ciullo, Stuart K. King, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J. Wouter Jukema, Nicole M. Probst-Hensch, Claudia Hundertmark, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R. Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, David S. Siscovick, Cornelia M. van Duijn, Ingrid Borecki, Meredith C. Foster, Sharon L. R. Kardia, Yongmei Liu, Gary C. Curhan, Igor Rudan, Ulf Gyllensten, James F. Wilson, Andre Franke, Peter P. Pramstaller, Rainer Retting, Inga Prokopenko, Conall M. O'Seaghdha, Jacqueline C. M. Witteman, Caroline Hayward, Paul Ridker, Afshin Parsa, Murielle Bochud, Iris M. Heid, Wolfram Goessling, Daniel I. Chasman, W. H. Linda Kao, Caroline S. Fox, Nicole Glazer, Aaron Isaacs, Ching-Ti Liu, Alexander Teumer, Albert V. Smith, Jeffrey R. O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Andrew D. Johnson, Hinco J. Gierman, Mary Feitosa, Shih-Jen Hwang, Elizabeth J. Atkinson, Maija Garnaas, Kurt Lohman, Marilyn C. Cornelis, Asa Johansson, Anke Tonjes, Abbas Dehghan, Vincent Chouraki, Elizabeth HollidayElizabeth Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimaki, Carsten A. Boger, Tonu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y. Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Christian Fuchsberger, Wellcome Trust Case Control Consortium 2 (WTCCC2), Tamara B. Harris, Lenore J. Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D. Mitchell, Eric Boerwinkle, Helena Schmidt, Matthias Olden, Margherita Cavalieri, Madhumathi Rao, Frank B. Hu, Ayse Demirkan, Ben A. Oostra, Mariza de Andrade, Stephen T. Turner, Jingzhong Ding, Jeanette S. Andrews, Barry I. Freedma, Ming-Huei Chen, Wolfgang Koenig, Thomas Illig, Angela Doring, H.-Erich Wichmann, Ivana Kolcic, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E. Wheeler, Wilmar Igl, Adrienne Tin, Ghazal Zaboli, Sarah H. Wild, Alan F. Wright, Harry Campbell, David Ellinghaus, Ute Nothlings, Gunnar Jacobs, Reiner Biffar, Karlhans Endlich, Florian Ernst, Daniel Taliun, Georg Homuth, Heyo K. Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Volker, Henry Volzke, Peter Kovacs, Michael Stumvoll, Reedik Magi, Albert HofmanChronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
History
Journal title
PLoS GeneticsVolume
8Issue
3Publisher
Public Library of ScienceLanguage
- en, English
