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

ICBP Consortium, 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 FuchsbergerBamidele 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, Caroline Hayward, Harry Campbell, Igor Rudan, James F Wilson, Nicholas G Martin, Nick Hastie, Ozren Polasek, Paul Mitchell, Sarah H Wild, Veronique Vitart

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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
JournalNature Communications
Publication statusPublished - 21 Jan 2016


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