Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals.
Winkler TW., Rasheed H., Teumer A., Gorski M., Rowan BX., Stanzick KJ., Thomas LF., Tin A., Hoppmann A., Chu AY., Tayo B., Thio CHL., Cusi D., Chai J-F., Sieber KB., Horn K., Li M., Scholz M., Cocca M., Wuttke M., van der Most PJ., Yang Q., Ghasemi S., Nutile T., Li Y., Pontali G., Günther F., Dehghan A., Correa A., Parsa A., Feresin A., de Vries APJ., Zonderman AB., Smith AV., Oldehinkel AJ., De Grandi A., Rosenkranz AR., Franke A., Teren A., Metspalu A., Hicks AA., Morris AP., Tönjes A., Morgan A., Podgornaia AI., Peters A., Körner A., Mahajan A., Campbell A., Freedman BI., Spedicati B., Ponte B., Schöttker B., Brumpton B., Banas B., Krämer BK., Jung B., Åsvold BO., Smith BH., Ning B., Penninx BWJH., Vanderwerff BR., Psaty BM., Kammerer CM., Langefeld CD., Hayward C., Spracklen CN., Robinson-Cohen C., Hartman CA., Lindgren CM., Wang C., Sabanayagam C., Heng C-K., Lanzani C., Khor C-C., Cheng C-Y., Fuchsberger C., Gieger C., Shaffer CM., Schulz C-A., Willer CJ., Chasman DI., Gudbjartsson DF., Ruggiero D., Toniolo D., Czamara D., Porteous DJ., Waterworth DM., Mascalzoni D., Mook-Kanamori DO., Reilly DF., Daw EW., Hofer E., Boerwinkle E., Salvi E., Bottinger EP., Tai E-S., Catamo E., Rizzi F., Guo F., Rivadeneira F., Guilianini F., Sveinbjornsson G., Ehret G., Waeber G., Biino G., Girotto G., Pistis G., Nadkarni GN., Delgado GE., Montgomery GW., Snieder H., Campbell H., White HD., Gao H., Stringham HM., Schmidt H., Li H., Brenner H., Holm H., Kirsten H., Kramer H., Rudan I., Nolte IM., Tzoulaki I., Olafsson I., Martins J., Cook JP., Wilson JF., Halbritter J., Felix JF., Divers J., Kooner JS., Lee JJ-M., O'Connell J., Rotter JI., Liu J., Xu J., Thiery J., Ärnlöv J., Kuusisto J., Jakobsdottir J., Tremblay J., Chambers JC., Whitfield JB., Gaziano JM., Marten J., Coresh J., Jonas JB., Mychaleckyj JC., Christensen K., Eckardt K-U., Mohlke KL., Endlich K., Dittrich K., Ryan KA., Rice KM., Taylor KD., Ho K., Nikus K., Matsuda K., Strauch K., Miliku K., Hveem K., Lind L., Wallentin L., Yerges-Armstrong LM., Raffield LM., Phillips LS., Launer LJ., Lyytikäinen L-P., Lange LA., Citterio L., Klaric L., Ikram MA., Ising M., Kleber ME., Francescatto M., Concas MP., Ciullo M., Piratsu M., Orho-Melander M., Laakso M., Loeffler M., Perola M., de Borst MH., Gögele M., Bianca ML., Lukas MA., Feitosa MF., Biggs ML., Wojczynski MK., Kavousi M., Kanai M., Akiyama M., Yasuda M., Nauck M., Waldenberger M., Chee M-L., Chee M-L., Boehnke M., Preuss MH., Stumvoll M., Province MA., Evans MK., O'Donoghue ML., Kubo M., Kähönen M., Kastarinen M., Nalls MA., Kuokkanen M., Ghanbari M., Bochud M., Josyula NS., Martin NG., Tan NYQ., Palmer ND., Pirastu N., Schupf N., Verweij N., Hutri-Kähönen N., Mononen N., Bansal N., Devuyst O., Melander O., Raitakari OT., Polasek O., Manunta P., Gasparini P., Mishra PP., Sulem P., Magnusson PKE., Elliott P., Ridker PM., Hamet P., Svensson PO., Joshi PK., Kovacs P., Pramstaller PP., Rossing P., Vollenweider P., van der Harst P., Dorajoo R., Sim RZH., Burkhardt R., Tao R., Noordam R., Mägi R., Schmidt R., de Mutsert R., Rueedi R., van Dam RM., Carroll RJ., Gansevoort RT., Loos RJF., Felicita SC., Sedaghat S., Padmanabhan S., Freitag-Wolf S., Pendergrass SA., Graham SE., Gordon SD., Hwang S-J., Kerr SM., Vaccargiu S., Patil SB., Hallan S., Bakker SJL., Lim S-C., Lucae S., Vogelezang S., Bergmann S., Corre T., Ahluwalia TS., Lehtimäki T., Boutin TS., Meitinger T., Wong T-Y., Bergler T., Rabelink TJ., Esko T., Haller T., Thorsteinsdottir U., Völker U., Foo VHX., Salomaa V., Vitart V., Giedraitis V., Gudnason V., Jaddoe VWV., Huang W., Zhang W., Wei WB., Kiess W., März W., Koenig W., Lieb W., Gao X., Sim X., Wang YX., Friedlander Y., Tham Y-C., Kamatani Y., Okada Y., Milaneschi Y., Yu Z., Lifelines cohort study None., DiscovEHR/MyCode study None., VA Million Veteran Program None., Stark KJ., Stefansson K., Böger CA., Hung AM., Kronenberg F., Köttgen A., Pattaro C., Heid IM.
Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.