title: Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
Creators: name: Gorski, Mathias
name: Jung, Bettina
name: Li, Yong
name: Matias-Garcia, Pamela R.
name: Wuttke, Matthias
name: Coassin, Stefan
name: Thio, Chris H. L.
name: Kleber, Marcus E.
name: Winkler, Thomas W.
name: Wanner, Veronika
name: Chai, Jin-Fang
name: Chu, Audrey Y.
name: Cocca, Massimiliano
name: Feitosa, Mary F.
name: Ghasemi, Sahar
name: Hoppmann, Anselm
name: Horn, Katrin
name: Li, Man
name: Nutile, Teresa
name: Scholz, Markus
name: Sieber, Karsten B.
name: Teumer, Alexander
name: Tin, Adrienne
name: Wang, Judy
name: Tayo, Bamidele O.
name: Ahluwalia, Tarunveer S.
name: Almgren, Peter
name: Bakker, Stephan J. L.
name: Banas, Bernhard
name: Bansal, Nisha
name: Biggs, Mary L.
name: Boerwinkle, Eric
name: Böttinger, Erwin Paul
name: Brenner, Hermann
name: Carroll, Robert J.
name: Chalmers, John
name: Chee, Miao-Li
name: Chee, Miao-Ling
name: Cheng, Ching-Yu
name: Coresh, Josef
name: de Borst, Martin H.
name: Degenhardt, Frauke
name: Eckardt, Kai-Uwe
name: Endlich, Karlhans
name: Franke, Andre
name: Freitag-Wolf, Sandra
name: Gampawar, Piyush
name: Gansevoort, Ron T.
name: Ghanbari, Mohsen
name: Gieger, Christian
name: Hamet, Pavel
name: Ho, Kevin
name: Hofer, Edith
name: Holleczek, Bernd
name: Foo, Valencia Hui Xian
name: Hutri-Kahonen, Nina
name: Hwang, Shih-Jen
name: Ikram, M. Arfan
name: Josyula, Navya Shilpa
name: Kahonen, Mika
name: Khor, Chiea-Chuen
name: Koenig, Wolfgang
name: Kramer, Holly
name: Kraemer, Bernhard K.
name: Kuehnel, Brigitte
name: Lange, Leslie A.
name: Lehtimaki, Terho
name: Lieb, Wolfgang
name: Loos, Ruth J. F.
name: Lukas, Mary Ann
name: Lyytikainen, Leo-Pekka
name: Meisinger, Christa
name: Meitinger, Thomas
name: Melander, Olle
name: Milaneschi, Yuri
name: Mishra, Pashupati P.
name: Mononen, Nina
name: Mychaleckyj, Josyf C.
name: Nadkarni, Girish N.
name: Nauck, Matthias
name: Nikus, Kjell
name: Ning, Boting
name: Nolte, Ilja M.
name: O'Donoghue, Michelle L.
name: Orho-Melander, Marju
name: Pendergrass, Sarah A.
name: Penninx, Brenda W. J. H.
name: Preuss, Michael H.
name: Psaty, Bruce M.
name: Raffield, Laura M.
name: Raitakari, Olli T.
name: Rettig, Rainer
name: Rheinberger, Myriam
name: Rice, Kenneth M.
name: Rosenkranz, Alexander R.
name: Rossing, Peter
name: Rotter, Jerome
name: Sabanayagam, Charumathi
name: Schmidt, Helena
name: Schmidt, Reinhold
name: Schoettker, Ben
name: Schulz, Christina-Alexandra
name: Sedaghat, Sanaz
name: Shaffer, Christian M.
name: Strauch, Konstantin
name: Szymczak, Silke
name: Taylor, Kent D.
name: Tremblay, Johanne
name: Chaker, Layal
name: van der Harst, Pim
name: van der Most, Peter J.
name: Verweij, Niek
name: Voelker, Uwe
name: Waldenberger, Melanie
name: Wallentin, Lars
name: Waterworth, Dawn M.
name: White, Harvey D.
name: Wilson, James G.
name: Wong, Tien-Yin
name: Woodward, Mark
name: Yang, Qiong
name: Yasuda, Masayuki
name: Yerges-Armstrong, Laura M.
name: Zhang, Yan
name: Snieder, Harold
name: Wanner, Christoph
name: Boger, Carsten A.
name: Kottgen, Anna
name: Kronenberg, Florian
name: Pattaro, Cristian
name: Heid, Iris M.
Publisher: name: Universität Potsdam
Year: 2023
Subjects: subject: 610 Medizin und Gesundheit

description: 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.
description: Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät; 19