| License: Creative Commons Attribution Non-commercial No Derivatives 4.0 PDF - Published Version (2MB) |
- URN to cite this document:
- urn:nbn:de:bvb:355-epub-528094
- DOI to cite this document:
- 10.5283/epub.52809
; Thomas, Laurent F. ; Graham, Sarah E. ; Sveinbjornsson, Gardar ; Winkler, Thomas W. ; Günther, Felix ; Stark, Klaus J. ; Chai, Jin-Fang ; Tayo, Bamidele O. ; Wuttke, Matthias ; Li, Yong ; Tin, Adrienne ; Ahluwalia, Tarunveer S. ; Ärnlöv, Johan ; Åsvold, Bjørn Olav
; Bakker, Stephan J. L. ; Banas, Bernhard
; Bansal, Nisha ; Biggs, Mary L. ; Biino, Ginevra ; Böhnke, Michael ; Boerwinkle, Eric ; Bottinger, Erwin P. ; Brenner, Hermann
; Brumpton, Ben
; Carroll, Robert J. ; Chaker, Layal
; Chalmers, John
; Chee, Miao-Li ; Chee, Miao-Ling ; Cheng, Ching-Yu ; Chu, Audrey Y. ; Ciullo, Marina ; Cocca, Massimiliano ; Cook, James P. ; Coresh, Josef ; Cusi, Daniele
; de Borst, Martin H. ; Degenhardt, Frauke ; Eckardt, Kai-Uwe ; Endlich, Karlhans ; Evans, Michele K. ; Feitosa, Mary F. ; Franke, Andre ; Freitag-Wolf, Sandra ; Fuchsberger, Christian ; Gampawar, Piyush ; Gansevoort, Ron T. ; Ghanbari, Mohsen
; Ghasemi, Sahar ; Giedraitis, Vilmantas ; Gieger, Christian ; Gudbjartsson, Daniel F. ; Hallan, Stein ; Hamet, Pavel ; Hishida, Asahi
; Ho, Kevin ; Hofer, Edith ; Holleczek, Bernd ; Holm, Hilma ; Hoppmann, Anselm ; Horn, Katrin ; Hutri-Kähönen, Nina ; Hveem, Kristian ; Hwang, Shih-Jen
; Ikram, M. Arfan ; Josyula, Navya Shilpa ; Jung, Bettina ; Kähönen, Mika
; Karabegović, Irma ; Khor, Chiea-Chuen ; Koenig, Wolfgang ; Kramer, Holly ; Krämer, Bernhard K. ; Kühnel, Brigitte ; Kuusisto, Johanna ; Laakso, Markku ; Lange, Leslie A. ; Lehtimäki, Terho
; Li, Man ; Lieb, Wolfgang ; Lind, Lars ; Lindgren, Cecilia M. ; Loos, Ruth J. F.
; Lukas, Mary Ann ; Lyytikäinen, Leo-Pekka ; Mahajan, Anubha ; Matias-Garcia, Pamela R. ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Milaneschi, Yuri ; Mishra, Pashupati P.
; Mononen, Nina ; Morris, Andrew P. ; Mychaleckyj, Josyf C. ; Nadkarni, Girish N. ; Naito, Mariko ; Nakatochi, Masahiro
; Nalls, Mike A. ; Nauck, Matthias ; Nikus, Kjell ; Ning, Boting ; Nolte, Ilja M. ; Nutile, Teresa ; O’Donoghue, Michelle L. ; O'Connell, Jeffrey R. ; Olafsson, Isleifur ; Orho-Melander, Marju ; Parsa, Afshin ; Pendergrass, Sarah A. ; Penninx, Brenda W. J. H. ; Pirastu, Mario ; Preuss, Michael H. ; Psaty, Bruce M. ; Raffield, Laura M. ; Raitakari, Olli T. ; Rheinberger, Myriam ; Rice, Kenneth M. ; Rizzi, Federica
; Rosenkranz, Alexander R. ; Rossing, Peter ; Rotter, Jerome I. ; Ruggiero, Daniela ; Ryan, Kathleen A. ; Sabanayagam, Charumathi ; Salvi, Erika
; Schmidt, Helena ; Schmidt, Reinhold ; Scholz, Markus ; Schöttker, Ben ; Schulz, Christina-Alexandra ; Sedaghat, Sanaz
; Shaffer, Christian M. ; Sieber, Karsten B. ; Sim, Xueling ; Sims, Mario ; Snieder, Harold ; Stanzick, Kira J. ; Thorsteinsdottir, Unnur ; Stocker, Hannah ; Strauch, Konstantin ; Stringham, Heather M. ; Sulem, Patrick ; Szymczak, Silke
; Taylor, Kent D. ; Thio, Chris H. L. ; Tremblay, Johanne ; Vaccargiu, Simona ; van der Harst, Pim
; van der Most, Peter J. ; Verweij, Niek
; Völker, Uwe ; Wakai, Kenji ; Waldenberger, Melanie ; Wallentin, Lars ; Wallner, Stefan ; Wang, Judy ; Waterworth, Dawn M. ; White, Harvey D. ; Willer, Cristen J. ; Wong, Tien-Yin ; Woodward, Mark
; Yang, Qiong ; Yerges-Armstrong, Laura M. ; Zimmermann, Martina E.
; Zonderman, Alan B.
; Bergler, Tobias ; Stefansson, Kari ; Böger, Carsten A. ; Pattaro, Cristian
; Köttgen, Anna ; Kronenberg, Florian ; Heid, Iris M. | Item type: | Article | ||||
|---|---|---|---|---|---|
| Open Access Type: | Hybrid Open Acces | ||||
| Journal or Publication Title: | Kidney International | ||||
| Publisher: | Elsevier | ||||
| Place of Publication: | NEW YORK | ||||
| Volume: | 102 | ||||
| Number of Issue or Book Chapter: | 3 | ||||
| Page Range: | pp. 624-639 | ||||
| Date: | 16 June 2022 | ||||
| Institutions: | Medicine > Abteilung für Nephrologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
| Projects (Historical): | SFB 1350 project identifier 387509280 (subproject C6 to IMH) | ||||
| Identification Number: |
| ||||
| Keywords: | CLINICAL-PRACTICE; BASE-LINE; DISEASE; PROGRESSION; SHROOM3; ADJUSTMENT; VARIANTS; EXAMPLE; RISK; BIAS; acute kidney injury; chronic kidney disease; diabetes; gene expression | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Partially | ||||
| Item ID: | 52809 |
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 ...

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.
Metadata last modified: 11 Dec 2024 06:53
Download Statistics