Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.kint.2020.09.030
Title: Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
Authors: 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
Xian Foo, V.H.
Hutri-Kähönen, N.
Hwang, Shih-Jen
Ikram, M. Arfan
Josyula, Navya Shilpa
Kähönen, M.
Khor, Chiea-Chuen
Koenig, Wolfgang
Kramer, Holly
Krämer, B.K.
Kühnel, B.
Lange, Leslie A.
Lehtimäki, T.
Lieb, Wolfgang
Alizadeh, B.Z.
Boezen, H.M.
Franke, L.
van der Harst, Pim
Navis, G.
Rots, M.
Snieder, Harold
Swertz, M.
Wolffenbuttel, B.H.R.
Wijmenga, C.
Abecasis, G.
Baras, A.
Cantor, M.
Coppola, G.
Economides, A.
Lotta, L.A.
Overton, J.D.
Reid, J.G.
Shuldiner, A.
Beechert, C.
Forsythe, C.
Fuller, E.D.
Gu, Z.
Lattari, M.
Lopez, A.
Schleicher, T.D.
Padilla, M.S.
Toledo, K.
Widom, L.
Wolf, S.E.
Pradhan, M.
Manoochehri, K.
Ulloa, R.H.
Bai, X.
Balasubramanian, S.
Barnard, L.
Blumenfeld, A.
Eom, G.
Habegger, L.
Hawes, A.
Khalid, S.
Maxwell, E.K.
Salerno, W.
Staples, J.C.
Jones, M.B.
Mitnaul, L.J.
Loos, Ruth J. F.
Lukas, Mary Ann
Lyytikäinen, L.-P.
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
Schöttker, B.
Schulz, Christina-Alexandra
Sedaghat, Sanaz
Shaffer, Christian M.
Strauch, Konstantin
Szymczak, Silke
Taylor, Kent D.
Tremblay, Johanne
Chaker, Layal
van der Most, Peter J.
Verweij, Niek
Völker, U.
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
Wanner, Christoph
Böger, C.A.
Köttgen, A.
Kronenberg, Florian
Pattaro, Cristian
Heid, Iris M.
Lifelines Cohort Study.
Regeneron Genetics Center.
Keywords: acute kidney injury
end-stage kidney disease
genome-wide association study
rapid eGFRcrea decline
Issue Date: 1-Apr-2021
Publisher: Elsevier B.V.
Citation: 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, Xian Foo, V.H., Hutri-Kähönen, N., Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, M., Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, B.K., Kühnel, B., Lange, Leslie A., Lehtimäki, T., Lieb, Wolfgang, Alizadeh, B.Z., Boezen, H.M., Franke, L., van der Harst, Pim, Navis, G., Rots, M., Snieder, Harold, Swertz, M., Wolffenbuttel, B.H.R., Wijmenga, C., Abecasis, G., Baras, A., Cantor, M., Coppola, G., Economides, A., Lotta, L.A., Overton, J.D., Reid, J.G., Shuldiner, A., Beechert, C., Forsythe, C., Fuller, E.D., Gu, Z., Lattari, M., Lopez, A., Schleicher, T.D., Padilla, M.S., Toledo, K., Widom, L., Wolf, S.E., Pradhan, M., Manoochehri, K., Ulloa, R.H., Bai, X., Balasubramanian, S., Barnard, L., Blumenfeld, A., Eom, G., Habegger, L., Hawes, A., Khalid, S., Maxwell, E.K., Salerno, W., Staples, J.C., Jones, M.B., Mitnaul, L.J., Loos, Ruth J. F., Lukas, Mary Ann, Lyytikäinen, L.-P., 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, Schöttker, B., Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Most, Peter J., Verweij, Niek, Völker, U., 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, Wanner, Christoph, Böger, C.A., Köttgen, A., Kronenberg, Florian, Pattaro, Cristian, Heid, Iris M., Lifelines Cohort Study., Regeneron Genetics Center. (2021-04-01). Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline. Kidney International 99 (4) : 926-939. ScholarBank@NUS Repository. https://doi.org/10.1016/j.kint.2020.09.030
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 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. © 2020 International Society of Nephrology
Source Title: Kidney International
URI: https://scholarbank.nus.edu.sg/handle/10635/233321
ISSN: 0085-2538
DOI: 10.1016/j.kint.2020.09.030
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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