Wiegrebe, Simon and Gorski, Mathias and Herold, Janina M. and Stark, Klaus J. and Thorand, Barbara and Gieger, Christian and Boeger, Carsten A. and Schoedel, Johannes and Hartig, Florian and Chen, Han and Winkler, Thomas W. and Kuechenhoff, Helmut and Heid, Iris M. (2024) Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline. NATURE COMMUNICATIONS, 15 (1): 10061. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally. The authors use longitudinal data from the UK Biobank to search for genetic variants associated with kidney function decline. Using a linear mixed model, they identify 13 independent variants, incl. 6 novel, and link them to genetics of kidney aging.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; POPULATION; HEALTH; CREATININE; TRANSPORT; DISEASE; |
| Subjects: | 500 Science > 580 Botanical sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie Biology, Preclinical Medicine > Institut für Pflanzenwissenschaften > Group Theoretical Ecology (Prof. Dr. Florian Hartig) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Nov 2025 09:13 |
| Last Modified: | 18 Nov 2025 09:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64434 |
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