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

Nat Commun 2016 Jan 21;7:10023. Epub 2016 Jan 21.

NHLBI's Framingham Heart Study and the Center for Population Studies, 73 Mt Wayte Avenue, Suite 2, Framingham, Massachusetts 01702, USA.

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.

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http://dx.doi.org/10.1038/ncomms10023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735748PMC

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January 2016
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