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

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Authors: Pattaro, C; Teumer, A; Gorski, M; Chu, A. Y.; Li, M; Mijatovic, V; Garnaas, M.; Tin, A; Sorice, R; Li, Y; Taliun, D; Olden, M; Foster, M.; Yang, Q; Chen, M. H.; Pers, T. H.; Johnson, A. D.; Ko, Y. A.; Fuchsberger, C; Tayo, B; Nalls, M.; Feitosa, M. F.; Isaacs, A; Dehghan, A; d'Adamo, P.; Adeyemo, A; Dieffenbach, A. K.; Zonderman, A. B.; Nolte, I. M.; van der Most, P. J.; Wright, A. F.; Shuldiner, A. R.; Morrison, A. C.; Hofman, A; Smith, A. V.; Dreisbach, A. W.; Franke, A; Uitterlinden, A. G.; Metspalu, A; Tonjes, A.; Lupo, A.; Robino, A; Johansson, A; Demirkan, A; Kollerits, B; Freedman, B. I.; Ponte, B; Oostra, B. A.; Paulweber, B; Kramer, B. K.; Mitchell, B. D.; Buckley, B. M.; Peralta, C. A.; Hayward, C; Helmer, C; Rotimi, C. N.; Shaffer, C. M.; Muller, C.; Sala, C; van Duijn, C. M.; Saint-Pierre, A.; Ackermann, D.; Shriner, D.; Ruggiero, D; Toniolo, D; Lu, Y; Cusi, D; Czamara, D.; Ellinghaus, D; Siscovick, D. S.; Ruderfer, D; Gieger, C; Grallert, H; Rochtchina, E.; Atkinson, E. J.; Holliday, E. G.; Boerwinkle, E; Salvi, E; Bottinger, E. P.; Murgia, F; Rivadeneira, F; Ernst, F; Kronenberg, F; Hu, F. B.; Navis, G. J.; Curhan, G. C.; Ehret, G. B.; Homuth, G; Coassin, S; Thun, G. A.; Pistis, G; Gambaro, G.; Malerba, G.; Montgomery, G. W.; Eiriksdottir, G; Jacobs, G; Li, G; Wichmann, H. E.; Campbell, H; Schmidt, H; Wallaschofski, H.; Volzke, H.; Brenner, H; Kroemer, H. K.; Kramer, H; Lin, H; Mateo Leach, I.; Ford, I; Guessous, I.; Rudan, I; Prokopenko, I; Borecki, I; Heid, I. M.; Kolcic, I; Persico, I.; Jukema, J. W.; Wilson, J. F.; Felix, J. F.; Divers, J; Lambert, J. C.; Stafford, J. M.; Gaspoz, J. M.; Smith, J. A.; Faul, J. D.; Wang, J. J.; Ding, J; Hirschhorn, J. N.; Attia, J; Whitfield, J. B.; Chalmers, J; Viikari, J; Coresh, J; Denny, J. C.; Karjalainen, J.; Fernandes, J. K.; Endlich, K; Butterbach, K.; Keene, K. L.; Lohman, K; Portas, L; Launer, L. J.; Lyytikainen, L. P.; Yengo, L; Franke, L.; Ferrucci, L; Rose, L. M.; Kedenko, L.; Rao, M; Struchalin, M; Kleber, M. E.; Cavalieri, M.; Haun, M; Cornelis, M. C.; Ciullo, M; Pirastu, M; de Andrade, M; McEvoy, M. A.; Woodward, M; Adam, M; Cocca, M; Nauck, M; Imboden, M; Waldenberger, M; Pruijm, M.; Metzger, M; Stumvoll, M; Evans, M. K.; Sale, M. M.; Kahonen, M.; Boban, M; Bochud, M; Rheinberger, M; Verweij, N; Bouatia-Naji, N.; Martin, N. G.; Hastie, N; Probst-Hensch, N; Soranzo, N; Devuyst, O; Raitakari, O; Gottesman, O; Franco, O. H.; Polasek, O; Gasparini, P; Munroe, P. B.; Ridker, P. M.; Mitchell, P; Muntner, P; Meisinger, C; Smit, J. H.; ICBP Consortium; AGEN Consortium; CARDIOGRAM; CHARGe-Heart Failure Group; ECHOGen Consortium; Kovacs, P; Wild, P. S.; Froguel, P; Rettig, R; Magi, R.; Biffar, R; Schmidt, R; Middelberg, R. P.; Carroll, R. J.; Penninx, B. W.; Scott, R. J.; Katz, R; Sedaghat, S; Wild, S. H.; Kardia, S. L.; Ulivi, S; Hwang, S. J.; Enroth, S; Kloiber, S.; Trompet, S; Stengel, B; Hancock, S. J.; Turner, S. T.; Rosas, S. E.; Stracke, S; Harris, T. B.; Zeller, T.; Zemunik, T; Lehtimaki, T.; Illig, T; Aspelund, T; Nikopensius, T; Esko, T; Tanaka, T; Gyllensten, U; Volker, U.; Emilsson, V.; Vitart, V; Aalto, V.; Gudnason, V; Chouraki, V; Chen, W. M.; Igl, W; Marz, W.; Koenig, W; Lieb, W; Loos, R. J.; Liu, Y; Snieder, H; Pramstaller, P. P.; Parsa, A; O'Connell, J. R.; Susztak, K; Hamet, P; Tremblay, J; de Boer, I. H.; Boger, C. A.; Goessling, W.; Chasman, D. I.; Kottgen, A.; Kao, W. H.; Fox, C. S.
Article Title: Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
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.
Journal Title: Nature communications
Volume: 7
ISSN: 2041-1723; 2041-1723
Publisher: Unknown  
Journal Place: England
Date Published: 2016
Start Page: 10023
Language: eng
DOI/URL:

10.1038/ncomms10023
Notes: LR: 20160305; GR: HHSN268201100009C/HL/NHLBI NIH HHS/United States; GR: K12 RR023250/RR/NCRR NIH HHS/United States; GR: R01 AG018728/AG/NIA NIH HHS/United States; GR: R01 DK058845/DK/NIDDK NIH HHS/United States; GR: R01 DK066574/DK/NIDDK NIH HHS/United States; GR: R01 DK084350/DK/NIDDK NIH HHS/United States; GR: R01 HL087641/HL/NHLBI NIH HHS/United States; GR: R01 HL087660/HL/NHLBI NIH HHS/United States; GR: R01 HL088119/HL/NHLBI NIH HHS/United States; GR: T32 HL007024/HL/NHLBI NIH HHS/United States; GR: U01 GM074518/GM/NIGMS NIH HHS/United States; GR: U01 HG004399/HG/NHGRI NIH HHS/United States; GR: U01 HG004402/HG/NHGRI NIH HHS/United States; GR: U01 HL072515/HL/NHLBI NIH HHS/United States; GR: U01 HL084756/HL/NHLBI NIH HHS/United States; GR: Z01 HG200362-01/Intramural NIH HHS/United States; JID: 101528555; NIHMS733914; OID: NLM: NIHMS733914; OID: NLM: PMC4735748; 2015/03/12 [received]; 2015/10/27 [accepted]; epublish