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

Authors:
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 Tayo, Michael 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 V 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 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, Guo Li, H-Erich Wichmann, Harry Campbell, Helena Schmidt, Henri Wallaschofski, Henry Völzke, Hermann Brenner, Heyo K Kroemer, Holly Kramer, Honghuang Lin, I Mateo Leach, Ian Ford, Idris Guessous, Igor Rudan, Inga Prokopenko, Ingrid 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 Probst-Hensch, Nicole Soranzo, Olivier Devuyst, Olli 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, - -, Peter Kovacs, Philipp S Wild, Philippe Froguel, Rainer Rettig, Reedik Mägi, Reiner Biffar, Reinhold Schmidt, Rita P S Middelberg, Robert J Carroll, Brenda W Penninx, Rodney J Scott, Ronit Katz, Sanaz Sedaghat, Sarah H Wild, Sharon L R Kardia, Sheila Ulivi, Shih-Jen Hwang, Stefan Enroth, Stefan Kloiber, Stella Trompet, Benedicte Stengel, Stephen J Hancock, Stephen T Turner, Sylvia E Rosas, Sylvia Stracke, Tamara B Harris, Tanja Zeller, Tatijana Zemunik, Terho Lehtimäki, Thomas Illig, Thor Aspelund, Tiit Nikopensius, Tonu Esko, Toshiko Tanaka, Ulf Gyllensten, Uwe Völker, Valur Emilsson, Veronique Vitart, Ville Aalto, Vilmundur Gudnason, Vincent Chouraki, Wei-Min Chen, Wilmar Igl, Winfried März, Wolfgang Koenig, Wolfgang Lieb, Ruth J F Loos, Yongmei Liu, Harold Snieder, Peter P Pramstaller, Afshin Parsa, Jeffrey R O'Connell, Katalin Susztak, Pavel Hamet, Johanne Tremblay, Ian H de Boer, Carsten A Böger, Wolfram Goessling, Daniel I Chasman, Anna Köttgen, W H Linda Kao, Caroline S Fox
Year of publication:
2016
Volume:
7
Issue:
-
Issn:
2041-1723
Journal title abbreviated:
NAT COMMUN
Journal title long:
Nature communications
Impact factor:
12.124
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.