@article {8879, title = {Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.}, journal = {Nat Commun}, volume = {7}, year = {2016}, month = {2016 Jan 21}, pages = {10023}, 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.

}, keywords = {Chronic disease, Genome-Wide Association Study, Genotype, Humans}, issn = {2041-1723}, doi = {10.1038/ncomms10023}, author = {Pattaro, Cristian and Teumer, Alexander and Gorski, Mathias and Chu, Audrey Y and Li, Man and Mijatovic, Vladan and Garnaas, Maija and Tin, Adrienne and Sorice, Rossella and Yong Li and Taliun, Daniel and Olden, Matthias and Foster, Meredith and Qiong Yang and Chen, Ming-Huei and Pers, Tune H and Andrew D Johnson and Ko, Yi-An and Fuchsberger, Christian and Bamidele O Tayo and Michael A Nalls and Feitosa, Mary F and Isaacs, Aaron and Dehghan, Abbas and d{\textquoteright}Adamo, Pio and Adebawole Adeyemo and Dieffenbach, Aida Karina and Alan B Zonderman and Ilja M Nolte and van der Most, Peter J and Alan F Wright and Alan R Shuldiner and Alanna C Morrison and Hofman, Albert and Albert Vernon Smith and Dreisbach, Albert W and Franke, Andre and Andr{\'e} G Uitterlinden and Andres Metspalu and T{\"o}njes, Anke and Lupo, Antonio and Robino, Antonietta and Johansson, {\r A}sa and Demirkan, Ayse and Kollerits, Barbara and Freedman, Barry I and Ponte, Belen and Ben A Oostra and Paulweber, Bernhard and Kr{\"a}mer, Bernhard K and Mitchell, Braxton D and Buckley, Brendan M and Peralta, Carmen A and Caroline Hayward and Helmer, Catherine and Charles N Rotimi and Shaffer, Christian M and M{\"u}ller, Christian and Cinzia Felicita Sala and Cornelia M van Duijn and Saint-Pierre, Aude and Daniel Ackermann and Daniel Shriner and Ruggiero, Daniela and Toniolo, Daniela and Lu, Yingchang and Cusi, Daniele and Czamara, Darina and Ellinghaus, David and David S Siscovick and Ruderfer, Douglas and Gieger, Christian and Grallert, Harald and Rochtchina, Elena and Atkinson, Elizabeth J and Holliday, Elizabeth G and Boerwinkle, Eric and Salvi, Erika and Erwin P Bottinger and Murgia, Federico and Fernando Rivadeneira and Ernst, Florian and Kronenberg, Florian and Hu, Frank B and Navis, Gerjan J and Curhan, Gary C and Georg B Ehret and Homuth, Georg and Coassin, Stefan and Thun, Gian-Andri and Pistis, Giorgio and Gambaro, Giovanni and Malerba, Giovanni and Grant W Montgomery and Gu{\dh}ny Eir{\'\i}ksd{\'o}ttir and Jacobs, Gunnar and Guo Li and Wichmann, H-Erich and Campbell, Harry and Schmidt, Helena and Wallaschofski, Henri and V{\"o}lzke, Henry and Brenner, Hermann and Kroemer, Heyo K and Kramer, Holly and Lin, Honghuang and Irene Mateo Leach and Ford, Ian and Guessous, Idris and Rudan, Igor and Prokopenko, Inga and Ingrid B Borecki and Iris M Heid and Kolcic, Ivana and Persico, Ivana and Jukema, J Wouter and James F Wilson and Felix, Janine F and Divers, Jasmin and Lambert, Jean-Charles and Stafford, Jeanette M and Gaspoz, Jean-Michel and Jennifer A Smith and Jessica Faul and Wang, Jie Jin and Ding, Jingzhong and Joel N Hirschhron and John R. Attia and Whitfield, John B and Chalmers, John and Viikari, Jorma and Coresh, Josef and Denny, Joshua C and Karjalainen, Juha and Fernandes, Jyotika K and Endlich, Karlhans and Butterbach, Katja and Keene, Keith L and Kurt Lohman and Portas, Laura and Lenore J Launer and Lyytik{\"a}inen, Leo-Pekka and Yengo, Loic and Lude L Franke and Luigi Ferrucci and Rose, Lynda M and Kedenko, Lyudmyla and Rao, Madhumathi and Struchalin, Maksim and Kleber, Marcus E and Cavalieri, Margherita and Haun, Margot and Marilyn C Cornelis and Ciullo, Marina and Pirastu, Mario and de Andrade, Mariza and McEvoy, Mark A and Woodward, Mark and Adam, Martin and Cocca, Massimiliano and Nauck, Matthias and Imboden, Medea and Waldenberger, Melanie and Pruijm, Menno and Metzger, Marie and Stumvoll, Michael and Michele K Evans and Sale, Michele M and K{\"a}h{\"o}nen, Mika and Boban, Mladen and Bochud, Murielle and Rheinberger, Myriam and Verweij, Niek and Bouatia-Naji, Nabila and Nicholas G Martin and Nicholas D Hastie and Nicole M Probst-Hensch and Soranzo, Nicole and Devuyst, Olivier and Olli T Raitakari and Gottesman, Omri and Franco, Oscar H and Polasek, Ozren and Paolo P. Gasparini and Munroe, Patricia B and Ridker, Paul M and Mitchell, Paul and Muntner, Paul and Meisinger, Christa and Johannes H Smit and Kovacs, Peter and Wild, Philipp S and Froguel, Philippe and Rettig, Rainer and M{\"a}gi, Reedik and Biffar, Reiner and Schmidt, Reinhold and Middelberg, Rita P S and Carroll, Robert J and Brenda W J H Penninx and Rodney J Scott and Katz, Ronit and Sedaghat, Sanaz and Sarah Wild and Sharon L R Kardia and Ulivi, Sheila and Hwang, Shih-Jen and Enroth, Stefan and Kloiber, Stefan and Trompet, Stella and Stengel, Benedicte and Hancock, Stephen J and Stephen T Turner and Rosas, Sylvia E and Stracke, Sylvia and Tamara B Harris and Zeller, Tanja and Zemunik, Tatijana and Lehtim{\"a}ki, Terho and Illig, Thomas and Aspelund, Thor and Nikopensius, Tiit and T{\~o}nu Esko and Toshiko Tanaka and Gyllensten, Ulf and V{\"o}lker, Uwe and Emilsson, Valur and Vitart, Veronique and Aalto, Ville and Gudnason, Vilmundur and Chouraki, Vincent and Chen, Wei-Min and Igl, Wilmar and M{\"a}rz, Winfried and Koenig, Wolfgang and Lieb, Wolfgang and Ruth J F Loos and Yongmei Liu and Snieder, Harold and Pramstaller, Peter P and Parsa, Afshin and Jeff O{\textquoteright}Connell and Susztak, Katalin and Hamet, Pavel and Tremblay, Johanne and de Boer, Ian H and B{\"o}ger, Carsten A and Goessling, Wolfram and Daniel I Chasman and K{\"o}ttgen, Anna and Kao, W H Linda and Caroline S Fox} }