Stanzick, Kira J. and Li, Yong and Schlosser, Pascal and Gorski, Mathias and Wuttke, Matthias and Thomas, Laurent F. and Rasheed, Humaira and Rowan, Bryce X. and Graham, Sarah E. and Vanderweff, Brett R. and Patil, Snehal B. and Robinson-Cohen, Cassiane and Gaziano, John M. and O'Donnell, Christopher J. and Willer, Cristen J. and Hallan, Stein and Asvold, Bjorn Olav and Gessner, Andre and Hung, Adriana M. and Pattaro, Cristian and Koettgen, Anna and Stark, Klaus J. and Heid, Iris M. and Winkler, Thomas W. (2021) Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals. NATURE COMMUNICATIONS, 12 (1): 4350. ISSN , 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n=1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n=1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, <= 5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n=460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up. Identifying causal variants and genes in genome-wide association studies remains a challenge, an issue that is ameliorated with larger sample sizes. Here the authors meta-analyze kidney function genome-wide association studies to identify new loci and fine-map loci to home in on variants and genes involved in kidney function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; SERUM CYSTATIN-C; FALSE DISCOVERY; ESTIMATING GFR; RARE VARIANTS; ASSOCIATION; CREATININE; STATISTICS; MASS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Institut für Epidemiologie und Präventivmedizin > Medical Sociology |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 06:40 |
| Last Modified: | 21 Sep 2022 06:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47773 |
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