A catalog of genetic loci associated with kidney function from analyses of a million individuals.
Wuttke M., Li Y., Li M., Sieber KB., Feitosa MF., Gorski M., Tin A., Wang L., Chu AY., Hoppmann A., Kirsten H., Giri A., Chai J-F., Sveinbjornsson G., Tayo BO., Nutile T., Fuchsberger C., Marten J., Cocca M., Ghasemi S., Xu Y., Horn K., Noce D., van der Most PJ., Sedaghat S., Yu Z., Akiyama M., Afaq S., Ahluwalia TS., Almgren P., Amin N., Ärnlöv J., Bakker SJL., Bansal N., Baptista D., Bergmann S., Biggs ML., Biino G., Boehnke M., Boerwinkle E., Boissel M., Bottinger EP., Boutin TS., Brenner H., Brumat M., Burkhardt R., Butterworth AS., Campana E., Campbell A., Campbell H., Canouil M., Carroll RJ., Catamo E., Chambers JC., Chee M-L., Chee M-L., Chen X., Cheng C-Y., Cheng Y., Christensen K., Cifkova R., Ciullo M., Concas MP., Cook JP., Coresh J., Corre T., Sala CF., Cusi D., Danesh J., Daw EW., de Borst MH., De Grandi A., de Mutsert R., de Vries APJ., Degenhardt F., Delgado G., Demirkan A., Di Angelantonio E., Dittrich K., Divers J., Dorajoo R., Eckardt K-U., Ehret G., Elliott P., Endlich K., Evans MK., Felix JF., Foo VHX., Franco OH., Franke A., Freedman BI., Freitag-Wolf S., Friedlander Y., Froguel P., Gansevoort RT., Gao H., Gasparini P., Gaziano JM., Giedraitis V., Gieger C., Girotto G., Giulianini F., Gögele M., Gordon SD., Gudbjartsson DF., Gudnason V., Haller T., Hamet P., Harris TB., Hartman CA., Hayward C., Hellwege JN., Heng C-K., Hicks AA., Hofer E., Huang W., Hutri-Kähönen N., Hwang S-J., Ikram MA., Indridason OS., Ingelsson E., Ising M., Jaddoe VWV., Jakobsdottir J., Jonas JB., Joshi PK., Josyula NS., Jung B., Kähönen M., Kamatani Y., Kammerer CM., Kanai M., Kastarinen M., Kerr SM., Khor C-C., Kiess W., Kleber ME., Koenig W., Kooner JS., Körner A., Kovacs P., Kraja AT., Krajcoviechova A., Kramer H., Krämer BK., Kronenberg F., Kubo M., Kühnel B., Kuokkanen M., Kuusisto J., La Bianca M., Laakso M., Lange LA., Langefeld CD., Lee JJ-M., Lehne B., Lehtimäki T., Lieb W., Lifelines Cohort Study None., Lim S-C., Lind L., Lindgren CM., Liu J., Liu J., Loeffler M., Loos RJF., Lucae S., Lukas MA., Lyytikäinen L-P., Mägi R., Magnusson PKE., Mahajan A., Martin NG., Martins J., März W., Mascalzoni D., Matsuda K., Meisinger C., Meitinger T., Melander O., Metspalu A., Mikaelsdottir EK., Milaneschi Y., Miliku K., Mishra PP., V. A. Million Veteran Program None., Mohlke KL., Mononen N., Montgomery GW., Mook-Kanamori DO., Mychaleckyj JC., Nadkarni GN., Nalls MA., Nauck M., Nikus K., Ning B., Nolte IM., Noordam R., O'Connell J., O'Donoghue ML., Olafsson I., Oldehinkel AJ., Orho-Melander M., Ouwehand WH., Padmanabhan S., Palmer ND., Palsson R., Penninx BWJH., Perls T., Perola M., Pirastu M., Pirastu N., Pistis G., Podgornaia AI., Polasek O., Ponte B., Porteous DJ., Poulain T., Pramstaller PP., Preuss MH., Prins BP., Province MA., Rabelink TJ., Raffield LM., Raitakari OT., Reilly DF., Rettig R., Rheinberger M., Rice KM., Ridker PM., Rivadeneira F., Rizzi F., Roberts DJ., Robino A., Rossing P., Rudan I., Rueedi R., Ruggiero D., Ryan KA., Saba Y., Sabanayagam C., Salomaa V., Salvi E., Saum K-U., Schmidt H., Schmidt R., Schöttker B., Schulz C-A., Schupf N., Shaffer CM., Shi Y., Smith AV., Smith BH., Soranzo N., Spracklen CN., Strauch K., Stringham HM., Stumvoll M., Svensson PO., Szymczak S., Tai E-S., Tajuddin SM., Tan NYQ., Taylor KD., Teren A., Tham Y-C., Thiery J., Thio CHL., Thomsen H., Thorleifsson G., Toniolo D., Tönjes A., Tremblay J., Tzoulaki I., Uitterlinden AG., Vaccargiu S., van Dam RM., van der Harst P., van Duijn CM., Velez Edward DR., Verweij N., Vogelezang S., Völker U., Vollenweider P., Waeber G., Waldenberger M., Wallentin L., Wang YX., Wang C., Waterworth DM., Bin Wei W., White H., Whitfield JB., Wild SH., Wilson JF., Wojczynski MK., Wong C., Wong T-Y., Xu L., Yang Q., Yasuda M., Yerges-Armstrong LM., Zhang W., Zonderman AB., Rotter JI., Bochud M., Psaty BM., Vitart V., Wilson JG., Dehghan A., Parsa A., Chasman DI., Ho K., Morris AP., Devuyst O., Akilesh S., Pendergrass SA., Sim X., Böger CA., Okada Y., Edwards TL., Snieder H., Stefansson K., Hung AM., Heid IM., Scholz M., Teumer A., Köttgen A., Pattaro C.
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.