Gorski, Mathias and Rasheed, Humaira and Teumer, Alexander and Thomas, Laurent F. and Graham, Sarah E. and Sveinbjornsson, Gardar and Winkler, Thomas W. and Guenther, Felix and Stark, Klaus J. and Chai, Jin-Fang and Tayo, Bamidele O. and Wuttke, Matthias and Li, Yong and Tin, Adrienne and Ahluwalia, Tarunveer S. and Arnlov, Johan and Asvold, Bjorn Olav and Bakker, Stephan J. L. and Banas, Bernhard and Bansal, Nisha and Biggs, Mary L. and Biino, Ginevra and Bohnke, Michael and Boerwinkle, Eric and Bottinger, Erwin P. and Brenner, Hermann and Brumpton, Ben and Carroll, Robert J. and Chaker, Layal and Chalmers, John and Chee, Miao-Li and Chee, Miao-Ling and Cheng, Ching-Yu and Chu, Audrey Y. and Ciullo, Marina and Cocca, Massimiliano and Cook, James P. and Coresh, Josef and Cusi, Daniele and de Borst, Martin H. and Degenhardt, Frauke and Eckardt, Kai-Uwe and Endlich, Karlhans and Evans, Michele K. and Feitosa, Mary F. and Franke, Andre and Freitag-Wolf, Sandra and Fuchsberger, Christian and Gampawar, Piyush and Gansevoort, Ron T. and Ghanbari, Mohsen and Ghasemi, Sahar and Giedraitis, Vilmantas and Gieger, Christian and Gudbjartsson, Daniel F. and Hallan, Stein and Hamet, Pavel and Hishida, Asahi and Ho, Kevin and Hofer, Edith and Holleczek, Bernd and Holm, Hilma and Hoppmann, Anselm and Horn, Katrin and Hutri-Kahonen, Nina and Hveem, Kristian and Hwang, Shih-Jen and Ikram, M. Arfan and Josyula, Navya Shilpa and Jung, Bettina and Kahonen, Mika and Karabegovic, Irma and Khor, Chiea-Chuen and Koenig, Wolfgang and Kramer, Holly and Kramer, Bernhard K. and Kuehnel, Brigitte and Kuusisto, Johanna and Laakso, Markku and Lange, Leslie A. and Lehtimaki, Terho and Li, Man and Lieb, Wolfgang and Lind, Lars and Lindgren, Cecilia M. and Loos, Ruth J. F. and Lukas, Mary Ann and Lyytikainen, Leo-Pekka and Mahajan, Anubha and Matias-Garcia, Pamela R. and Meisinger, Christa and Meitinger, Thomas and Melander, Olle and Milaneschi, Yuri and Mishra, Pashupati P. and Mononen, Nina and Morris, Andrew P. and Mychaleckyj, Josyf C. and Nadkarni, Girish N. and Naito, Mariko and Nakatochi, Masahiro and Nalls, Mike A. and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Nolte, Ilja M. and Nutile, Teresa and O'Donoghue, Michelle L. and O'Connell, Jeffrey and Olafsson, Isleifur and Orho-Melander, Marju and Parsa, Afshin and Pendergrass, Sarah A. and Penninx, Brenda W. J. H. and Pirastu, Mario and Preuss, Michael H. and Psaty, Bruce M. and Raffield, Laura M. and Raitakari, Olli T. and Rheinberger, Myriam and Rice, Kenneth M. and Rizzi, Federica and Rosenkranz, Alexander R. and Rossing, Peter and Rotter, Jerome I. and Ruggiero, Daniela and Ryan, Kathleen A. and Sabanayagam, Charumathi and Salvi, Erika and Schmidt, Helena and Schmidt, Reinhold and Scholz, Markus and Schoettker, Ben and Schulz, Christina-Alexandra and Sedaghat, Sanaz and Shaffer, Christian M. and Sieber, Karsten B. and Sim, Xueling and Sims, Mario and Snieder, Harold and Stanzick, Kira J. and Thorsteinsdottir, Unnur and Stocker, Hannah and Strauch, Konstantin and Stringham, Heather M. and Sulem, Patrick and Szymczak, Silke and Taylor, Kent D. and Thio, Chris H. L. and Tremblay, Johanne and Vaccargiu, Simona and van der Harst, Pim and van der Most, Peter J. and Verweij, Niek and Volker, Uwe and Wakai, Kenji and Waldenberger, Melanie and Wallentin, Lars and Wallner, Stefan and Wang, Judy and Waterworth, Dawn M. and White, Harvey D. and Willer, Cristen J. and Wong, Tien-Yin and Woodward, Mark and Yang, Qiong and Yerges-Armstrong, Laura M. and Zimmermann, Martina and Zonderman, Alan B. and Bergler, Tobias and Stefansson, Kari and Boger, Carsten A. and Pattaro, Cristian and Koettgen, Anna and Kronenberg, Florian and Heid, Iris M. (2022) Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies. KIDNEY INTERNATIONAL, 102 (3). pp. 624-639. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics. Copyright (C) 2022, International Society of Nephrology. Published by Elsevier Inc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLINICAL-PRACTICE; BASE-LINE; DISEASE; PROGRESSION; SHROOM3; ADJUSTMENT; VARIANTS; EXAMPLE; RISK; BIAS; acute kidney injury; chronic kidney disease; diabetes; gene expression |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Sep 2023 12:54 |
| Last Modified: | 19 Sep 2023 12:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58812 |
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