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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 |
Appears in Collections: | Staff Publications Elements |
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