Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Cristian Pattaro, Alexander Teumer, Mathias Gorski, Audrey Y. Chu, Man Li, Vladan Mijatovic, Maija Garnaas, Adrienne Tin, Rossella Sorice, Yong Li, Daniel Taliun, Matthias Olden, Meredith Foster, Qiong Yang, Ming Huei Chen, Tune H. Pers, Andrew D. Johnson, Yi An Ko, Christian Fuchsberger, Bamidele TayoMichael A. Nalls, Mary F. Feitosa, Aaron Isaacs, Abbas Dehghan, Pio D'Adamo, Adebowale Adeyemo, Aida Karina Dieffenbach, Alan B. Zonderman, Ilja M. Nolte, Peter J. Van Der Most, Alan F. Wright, Alan R. Shuldiner, Alanna C. Morrison, Albert Hofman, Albert Vernon Smith, Albert W. Dreisbach, Andre Franke, Andre G. Uitterlinden, Andres Metspalu, Anke Tonjes, Antonio Lupo, Antonietta Robino, Åsa Johansson, Ayse Demirkan, Barbara Kollerits, Barry I. Freedman, Belen Ponte, Ben A. Oostra, Bernhard Paulweber, Bernhard K. Krämer, Braxton D. Mitchell, Brendan M. Buckley, Carmen A. Peralta, Caroline Hayward, Catherine Helmer, Charles N. Rotimi, Christian M. Shaffer, Christian Müller, Cinzia Sala, Cornelia M. van Duijn, Aude Saint-Pierre, Daniel Ackermann, Daniel Shriner, Daniela Ruggiero, Daniela Toniolo, Yingchang Lu, Daniele Cusi, Darina Czamara, David Ellinghaus, David S. Siscovick, Douglas M. Ruderfer, Christian Gieger, Harald Grallert, Elena Rochtchina, Elizabeth J. Atkinson, Elizabeth G. Holliday, Eric Boerwinkle, Erika Salvi, Erwin P. Bottinger, Federico Murgia, Fernando Rivadeneira, Florian Ernst, Florian Kronenberg, Frank B. Hu, Gerjan J. Navis, Gary C. Curhan, George B. Ehret, Georg Homuth, Stefan Coassin, Gian Andri Thun, Giorgio Pistis, Giovanni Gambaro, Giovanni Malerba, Grant W. Montgomery, Gudny Eiriksdottir, Gunnar Jacobs, Bao Guo Li, Heinz Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K. Kroemer, Holly Kramer, Honghuang Lin, Irene Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid B. Borecki, Iris M. Heid, Ivana Kolcic, Ivana Persico, J. Wouter Jukema, James F. Wilson, Janine F. Felix, Jasmin Divers, Jean Charles Lambert, Jeanette M. Stafford, Jean Michel Gaspoz, Jennifer A. Smith, Jessica D. Faul, Jie Jin Wang, Jingzhong Ding, Joel N. Hirschhorn, John Attia, John B. Whitfield, John Chalmers, Jorma Viikari, Josef Coresh, Joshua C. Denny, Juha Karjalainen, Jyotika K. Fernandes, Karlhans Endlich, Katja Butterbach, Keith L. Keene, Kurt Lohman, Laura Portas, Lenore J. Launer, Leo Pekka Lyytikäinen, Loic Yengo, Lude Franke, Luigi Ferrucci, Lynda M. Rose, Lyudmyla Kedenko, Madhumathi Rao, Maksim Struchalin, Marcus E. Kleber, Margherita Cavalieri, Margot Haun, Marilyn C. Cornelis, Marina Ciullo, Mario Pirastu, Mariza De Andrade, Mark A. McEvoy, Mark Woodward, Martin Adam, Massimiliano Cocca, Matthias Nauck, Medea Imboden, Melanie Waldenberger, Menno Pruijm, Marie Metzger, Michael Stumvoll, Michele K. Evans, Michele M. Sale, Mika Kähönen, Mladen Boban, Murielle Bochud, Myriam Rheinberger, Niek Verweij, Nabila Bouatia-Naji, Nicholas G. Martin, Nick Hastie, Nicole M. Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli T. Raitakari, Omri Gottesman, Oscar H. Franco, Ozren Polasek, Paolo Gasparini, Patricia B. Munroe, Paul M. Ridker, Paul Mitchell, Paul Muntner, Christa Meisinger, Johannes H. Smit, Goncalo R. Abecasis, Linda S. Adair, Myriam Alexander, David Altshuler, Najaf Amin, Dan E. Arking, Pankaj Arora, Yurii Aulchenko, Stephan J L Bakker, Stefania Bandinelli, Ines Barroso, Jacques S. Beckmann, John P. Beilby, Richard N. Bergman, Sven Bergmann, Joshua C. Bis, Michael Boehnke, Lori L. Bonnycastle, Stefan R. Bornstein, Michiel L. Bots, Jennifer L. Bragg-Gresham, Stefan Martin Brand, Eva Brand, Peter S. Braund, Morris J. Brown, Paul R. Burton, Juan P. Casas, Mark J. Caulfield, Aravinda Chakravarti, John C. Chambers, Giriraj R. Chandak, Yen Pei C. Chang, Fadi J. Charchar, Nish Chaturvedi, Yoon Shin Cho, Robert B Clarke, Francis S. Collins, Rory Collins, John M. Connell, Jackie A. Cooper, Matthew N. Cooper, Richard S. Cooper, Anna Maria Corsi, Marcus Dörr, Santosh Dahgam, John Danesh, George Davey Smith, Ian N.M. Day, Panos Deloukas, Matthew Denniff, Anna F. Dominiczak, Yanbin Dong, Ayo Doumatey, Paul Elliott, Roberto Elosua, Jeanette Erdmann, Susana Eyheramendy, Martin Farrall, Robert W. Lawrence, Lyle J. Palmer, ICBP Consortium, AGEN Consortium, CARDIOGRAM, CHARGe-Heart Failure Group, ECHOGen Consortium

Research output: Contribution to journalArticlepeer-review

376 Citations (Scopus)

Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Original languageEnglish
Article number10023
Number of pages19
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 21 Jan 2016

Fingerprint

Dive into the research topics of 'Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function'. Together they form a unique fingerprint.

Cite this