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

TitleGenetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
Publication TypeJournal Article
Year of Publication2016
AuthorsPattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, MA, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AKarina, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, A, Hofman, A, Smith, AVernon, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tönjes, A, Lupo, A, Robino, A, Johansson, Å, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Krämer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Müller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, G, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Völzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, I Leach, M, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, IB, Heid, IM, Kolcic, I, Persico, I, J Jukema, W, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJin, Ding, J, Hirschhorn, J, Attia, JR, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikäinen, L-P, Yengo, L, Franke, LL, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, M, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kähönen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, OT, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, J, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Mägi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, S, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimäki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Völker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, März, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Böger, CA, Goessling, W, Chasman, DI, Köttgen, A, Kao, WHLinda, Fox, CS
Corporate AuthorsICBP Consortium, AGEN Consortium, CARDIOGRAM, CHARGe-Heart Failure Group, ECHOGen Consortium
JournalNat Commun
Volume7
Pagination10023
Date Published2016 Jan 21
ISSN Number2041-1723
KeywordsChronic disease, Genome-Wide Association Study, Genotype, Humans
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.

DOI10.1038/ncomms10023
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/26831199?dopt=Abstract

Alternate JournalNat Commun
Citation Key8879
PubMed ID26831199
PubMed Central IDPMC4735748
Grant ListR01 MD009055 / MD / NIMHD NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
K12 RR023250 / RR / NCRR NIH HHS / United States
R01DK090311 / DK / NIDDK NIH HHS / United States
R24 OD017870 / OD / NIH HHS / United States
DP3 DK108220 / DK / NIDDK NIH HHS / United States
R01 HL087660 / HL / NHLBI NIH HHS / United States
P30 DK079637 / DK / NIDDK NIH HHS / United States
T32 HL007024 / HL / NHLBI NIH HHS / United States
P30 DK079626 / DK / NIDDK NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
U01 HL084756 / HL / NHLBI NIH HHS / United States
R01 DK084350 / DK / NIDDK NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
Z01 HG200362-01 / / Intramural NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
MC_PC_U127561128 / / Medical Research Council / United Kingdom
U01 HL072515 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
MR/K006584/1 / / Medical Research Council / United Kingdom
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 DK066574 / DK / NIDDK NIH HHS / United States
R01 DK090311 / DK / NIDDK NIH HHS / United States
F31 AG044879 / AG / NIA NIH HHS / United States
R01 AG018728 / AG / NIA NIH HHS / United States
U01 HG004399 / HG / NHGRI NIH HHS / United States
U01 GM074518 / GM / NIGMS NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
R24OD017870 / OD / NIH HHS / United States