Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
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Published:2022-06-13
Issue:1
Volume:5
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Winkler Thomas W.ORCID, Rasheed HumairaORCID, Teumer AlexanderORCID, Gorski Mathias, Rowan Bryce X., Stanzick Kira J., Thomas Laurent F., Tin AdrienneORCID, Hoppmann Anselm, Chu Audrey Y., Tayo Bamidele, Thio Chris H. L., Cusi Daniele, Chai Jin-Fang, Sieber Karsten B., Horn Katrin, Li Man, Scholz Markus, Cocca MassimilianoORCID, Wuttke Matthias, van der Most Peter J.ORCID, Yang QiongORCID, Ghasemi Sahar, Nutile Teresa, Li YongORCID, Pontali GiuliaORCID, Günther Felix, Dehghan AbbasORCID, Correa Adolfo, Parsa Afshin, Feresin Agnese, de Vries Aiko P. J., Zonderman Alan B., Smith Albert V.ORCID, Oldehinkel Albertine J., De Grandi Alessandro, Rosenkranz Alexander R., Franke AndreORCID, Teren Andrej, Metspalu AndresORCID, Hicks Andrew A.ORCID, Morris Andrew P., Tönjes Anke, Morgan Anna, Podgornaia Anna I., Peters Annette, Körner Antje, Mahajan Anubha, Campbell Archie, Freedman Barry I.ORCID, Spedicati BeatriceORCID, Ponte Belen, Schöttker Ben, Brumpton BenORCID, Banas Bernhard, Krämer Bernhard K., Jung Bettina, Åsvold Bjørn OlavORCID, Smith Blair H.ORCID, Ning Boting, Penninx Brenda W. J. H., Vanderwerff Brett R., Psaty Bruce M.ORCID, Kammerer Candace M., Langefeld Carl D.ORCID, Hayward CarolineORCID, Spracklen Cassandra N.ORCID, Robinson-Cohen Cassianne, Hartman Catharina A., Lindgren Cecilia M., Wang ChaolongORCID, Sabanayagam CharumathiORCID, Heng Chew-KiatORCID, Lanzani Chiara, Khor Chiea-ChuenORCID, Cheng Ching-YuORCID, Fuchsberger Christian, Gieger ChristianORCID, Shaffer Christian M., Schulz Christina-Alexandra, Willer Cristen J.ORCID, Chasman Daniel I., Gudbjartsson Daniel F., Ruggiero Daniela, Toniolo Daniela, Czamara DarinaORCID, Porteous David J.ORCID, Waterworth Dawn M., Mascalzoni DeborahORCID, Mook-Kanamori Dennis O., Reilly Dermot F., Daw E. Warwick, Hofer Edith, Boerwinkle Eric, Salvi Erika, Bottinger Erwin P., Tai E-ShyongORCID, Catamo Eulalia, Rizzi FedericaORCID, Guo Feng, Rivadeneira FernandoORCID, Guilianini Franco, Sveinbjornsson Gardar, Ehret Georg, Waeber Gerard, Biino Ginevra, Girotto Giorgia, Pistis Giorgio, Nadkarni Girish N., Delgado Graciela E., Montgomery Grant W.ORCID, Snieder HaroldORCID, Campbell Harry, White Harvey D., Gao He, Stringham Heather M.ORCID, Schmidt HelenaORCID, Li Hengtong, Brenner Hermann, Holm HilmaORCID, Kirsten Holgen, Kramer Holly, Rudan Igor, Nolte Ilja M., Tzoulaki Ioanna, Olafsson Isleifur, Martins JadeORCID, Cook James P., Wilson James F.ORCID, Halbritter Jan, Felix Janine F.ORCID, Divers Jasmin, Kooner Jaspal S.ORCID, Lee Jeannette Jen-Mai, O’Connell Jeffrey, Rotter Jerome I., Liu JianjunORCID, Xu Jie, Thiery Joachim, Ärnlöv Johan, Kuusisto Johanna, Jakobsdottir Johanna, Tremblay Johanne, Chambers John C., Whitfield John B., Gaziano John M., Marten Jonathan, Coresh JosefORCID, Jonas Jost B.ORCID, Mychaleckyj Josyf C.ORCID, Christensen KaareORCID, Eckardt Kai-Uwe, Mohlke Karen L.ORCID, Endlich Karlhans, Dittrich Katalin, Ryan Kathleen A.ORCID, Rice Kenneth M.ORCID, Taylor Kent D., Ho Kevin, Nikus Kjell, Matsuda Koichi, Strauch Konstantin, Miliku Kozeta, Hveem Kristian, Lind Lars, Wallentin Lars, Yerges-Armstrong Laura M.ORCID, Raffield Laura M.ORCID, Phillips Lawrence S., Launer Lenore J.ORCID, Lyytikäinen Leo-Pekka, Lange Leslie A., Citterio Lorena, Klaric Lucija, Ikram M. ArfanORCID, Ising Marcus, Kleber Marcus E., Francescatto Margherita, Concas Maria Pina, Ciullo Marina, Piratsu Mario, Orho-Melander Marju, Laakso MarkkuORCID, Loeffler Markus, Perola Markus, de Borst Martin H.ORCID, Gögele MartinORCID, Bianca Martina La, Lukas Mary Ann, Feitosa Mary F., Biggs Mary L., Wojczynski Mary K.ORCID, Kavousi Maryam, Kanai MasahiroORCID, Akiyama Masato, Yasuda Masayuki, Nauck Matthias, Waldenberger MelanieORCID, Chee Miao-Li, Chee Miao-Ling, Boehnke MichaelORCID, Preuss Michael H.ORCID, Stumvoll MichaelORCID, Province Michael A., Evans Michele K., O’Donoghue Michelle L., Kubo MichiakiORCID, Kähönen Mika, Kastarinen Mika, Nalls Mike A., Kuokkanen Mikko, Ghanbari MohsenORCID, Bochud Murielle, Josyula Navya ShilpaORCID, Martin Nicholas G.ORCID, Tan Nicholas Y. Q., Palmer Nicholette D., Pirastu NicolaORCID, Schupf Nicole, Verweij Niek, Hutri-Kähönen Nina, Mononen Nina, Bansal Nisha, Devuyst Olivier, Melander Olle, Raitakari Olli T., Polasek Ozren, Manunta Paolo, Gasparini Paolo, Mishra Pashupati P., Sulem PatrickORCID, Magnusson Patrik K. E., Elliott Paul, Ridker Paul M., Hamet Pavel, Svensson Per O., Joshi Peter K.ORCID, Kovacs PeterORCID, Pramstaller Peter P., Rossing PeterORCID, Vollenweider Peter, van der Harst Pim, Dorajoo RajkumarORCID, Sim Ralene Z. H., Burkhardt Ralph, Tao Ran, Noordam RaymondORCID, Mägi Reedik, Schmidt Reinhold, de Mutsert Renée, Rueedi Rico, van Dam Rob M., Carroll Robert J., Gansevoort Ron T., Loos Ruth J. F.ORCID, Felicita Sala Cinzia, Sedaghat Sanaz, Padmanabhan Sandosh, Freitag-Wolf Sandra, Pendergrass Sarah A., Graham Sarah E.ORCID, Gordon Scott D.ORCID, Hwang Shih-Jen, Kerr Shona M.ORCID, Vaccargiu Simona, Patil Snehal B., Hallan Stein, Bakker Stephan J. L., Lim Su-Chi, Lucae Susanne, Vogelezang Suzanne, Bergmann SvenORCID, Corre Tanguy, Ahluwalia Tarunveer S.ORCID, Lehtimäki TerhoORCID, Boutin Thibaud S.ORCID, Meitinger Thomas, Wong Tien-Yin, Bergler Tobias, Rabelink Ton J.ORCID, Esko Tõnu, Haller Toomas, Thorsteinsdottir Unnur, Völker UweORCID, Foo Valencia Hui Xian, Salomaa VeikkoORCID, Vitart VeroniqueORCID, Giedraitis Vilmantas, Gudnason VilmundurORCID, Jaddoe Vincent W. V.ORCID, Huang Wei, Zhang WeihuaORCID, Wei Wen Bin, Kiess Wieland, März Winfried, Koenig WolfgangORCID, Lieb WolfgangORCID, Gao Xin, Sim XuelingORCID, Wang Ya XingORCID, Friedlander Yechiel, Tham Yih-ChungORCID, Kamatani YoichiroORCID, Okada YukinoriORCID, Milaneschi Yuri, Yu ZhiORCID, Thio Chris H. L., van der Most Peter J., de Borst Martin H., Ho Kevin, Josyula Navya Shilpa, Pendergrass Sarah A., Rowan Bryce X., Robinson-Cohen Cassianne, Gaziano John M., Phillips Lawrence S., Tao Ran, Hung Adriana M., Stark Klaus J., Stefansson KariORCID, Böger Carsten A., Hung Adriana M., Kronenberg FlorianORCID, Köttgen AnnaORCID, Pattaro CristianORCID, Heid Iris M.ORCID, , ,
Abstract
AbstractReduced 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.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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