Gorski, Mathias; Jung, Bettina; Li, Yong; Matias-Garcia, Pamela R.; Wuttke, Matthias; Coassin, Stefan; Thio, Chris H. L.; Kleber, Marcus E.; Winkler, Thomas W.; Wanner, Veronika; Chai, Jin-Fang; Chu, Audrey Y.; Cocca, Massimiliano; Feitosa, Mary F.; Ghasemi, Sahar; Hoppmann, Anselm; Horn, Katrin; Li, Man; Nutile, Teresa; Scholz, Markus; Sieber, Karsten B.; Teumer, Alexander; Tin, Adrienne; Wang, Judy; Tayo, Bamidele O.; Ahluwalia, Tarunveer S.; Almgren, Peter; Bakker, Stephan J. L.; Banas, Bernhard; Bansal, Nisha; Biggs, Mary L.; Boerwinkle, Eric; Bottinger, Erwin P.; Brenner, Hermann; Carroll, Robert J.; Chalmers, John; Chee, Miao-Li; Chee, Miao-Ling; Cheng, Ching-Yu; Coresh, Josef; de Borst, Martin H.; Degenhardt, Frauke; Eckardt, Kai-Uwe; Endlich, Karlhans; Franke, Andre; Freitag-Wolf, Sandra; Gampawar, Piyush; Gansevoort, Ron T.; Ghanbari, Mohsen; Gieger, Christian; Hamet, Pavel; Ho, Kevin; Hofer, Edith; Holleczek, Bernd; Foo, Valencia Hui Xian; Hutri-Kahonen, Nina; Hwang, Shih-Jen; Ikram, M. Arfan; Josyula, Navya Shilpa; Kahonen, Mika; Khor, Chiea-Chuen; Koenig, Wolfgang; Kramer, Holly; Kraemer, Bernhard K.; Kuehnel, Brigitte; Lange, Leslie A.; Lehtimaki, Terho; Lieb, Wolfgang; Loos, Ruth J. F.; Lukas, Mary Ann; Lyytikainen, Leo-Pekka; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Milaneschi, Yuri; Mishra, Pashupati P.; Mononen, Nina; Mychaleckyj, Josyf C.; Nadkarni, Girish N.; Nauck, Matthias; Nikus, Kjell; Ning, Boting; Nolte, Ilja M.; O'Donoghue, Michelle L.; Orho-Melander, Marju; Pendergrass, Sarah A.; Penninx, Brenda W. J. H.; Preuss, Michael H.; Psaty, Bruce M.; Raffield, Laura M.; Raitakari, Olli T.; Rettig, Rainer; Rheinberger, Myriam; Rice, Kenneth M.; Rosenkranz, Alexander R.; Rossing, Peter; Rotter, Jerome I.; Sabanayagam, Charumathi; Schmidt, Helena; Schmidt, Reinhold; Schoettker, Ben; Schulz, Christina-Alexandra; Sedaghat, Sanaz; Shaffer, Christian M.; Strauch, Konstantin; Szymczak, Silke; Taylor, Kent D.; Tremblay, Johanne; Chaker, Layal; Harst, Pim van der; Most, Peter J. van der; Verweij, Niek; Voelker, Uwe; Waldenberger, Melanie; Wallentin, Lars; Waterworth, Dawn M.; White, Harvey D.; Wilson, James G.; Wong, Tien-Yin; Woodward, Mark; Yang, Qiong; Yasuda, Masayuki; Yerges-Armstrong, Laura M.; Zhang, Yan; Snieder, Harold; Wanner, Christoph; Boger, Carsten A.; Kottgen, Anna; Kronenberg, Florian; Pattaro, Cristian und Heid, Iris M.
(2021):
Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.
In: Kidney International, Bd. 99, Nr. 4: S. 926-939
Volltext auf 'Open Access LMU' nicht verfügbar.
Abstract
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more (Rapid3;encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline (CKDi25;encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
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