Gorski, Mathias and Tin, Adrienne and Garnaas, Maija and McMahon, Gearoid M. and Chu, Audrey Y. and Tayo, Bamidele O. and Pattaro, Cristian and Teumer, Alexander and Chasman, Daniel I. and Chalmers, John and Hamet, Pavel and Tremblay, Johanne and Woodward, Marc and Aspelund, Thor and Eiriksdottir, Gudny and Gudnason, Vilmundur and Harris, Tamara B. and Launer, Lenore J. and Smith, Albert V. and Mitchell, Braxton D. and O'Connell, Jeffrey R. and Shuldiner, Alan R. and Coresh, Josef and Li, Man and Freudenberger, Paul and Hofer, Edith and Schmidt, Helena and Schmidt, Reinhold and Holliday, Elizabeth G. and Mitchell, Paul and Wang, Jie Jin and de Boer, Ian H. and Li, Guo and Siscovick, David S. and Kutalik, Zoltan and Corre, Tanguy and Vollenweider, Peter and Waeber, Gerard and Gupta, Jayanta and Kanetsky, Peter A. and Hwang, Shih-Jen and Olden, Matthias and Yang, Qiong and de Andrade, Mariza and Atkinson, Elizabeth J. and Kardia, Sharon L. R. and Turner, Stephen T. and Stafford, Jeanette M. and Ding, Jingzhong and Liu, Yongmei and Barlassina, Cristina and Cusi, Daniele and Salvi, Erika and Staessen, Jan A. and Ridker, Paul M. and Grallert, Harald and Meisinger, Christa and Mueller-Nurasyid, Martina and Kraemer, Bernhard K. and Kramer, Holly and Rosas, Sylvia E. and Nolte, Ilja M. and Penninx, Brenda W. and Snieder, Harold and Del Greco, M. Fabiola and Franke, Andre and Noethlings, Ute and Lieb, Wolfgang and Bakker, Stephan J. L. and Gansevoort, Ron T. and van der Harst, Pim and Dehghan, Abbas and Franco, Oscar H. and Hofman, Albert and Rivadeneira, Fernando and Sedaghat, Sanaz and Uitterlinden, Andre G. and Coassin, Stefan and Haun, Margot and Kollerits, Barbara and Kronenberg, Florian and Paulweber, Bernhard and Aumann, Nicole and Endlich, Karlhans and Pietzner, Mike and Voelker, Uwe and Rettig, Rainer and Chouraki, Vincent and Helmer, Catherine and Lambert, Jean-Charles and Metzger, Marie and Stengel, Benedicte and Lehtimaki, Terho and Lyytikainen, Leo-Pekka and Raitakari, Olli and Johnson, Andrew and Parsa, Afshin and Bochud, Murielle and Heid, Iris M. and Goessling, Wolfram and Kottgen, Anna and Kao, W. H. Linda and Fox, Caroline S. and Boeger, Carsten A. (2015) Genome-wide association study of kidney function decline in individuals of European descent. KIDNEY INTERNATIONAL, 87 (5). pp. 1017-1029. ISSN 0085-2538, 1523-1755
Full text not available from this repository. (Request a copy)Abstract
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; SYNDROME TYPE 1D; HYPERTENSIVE NEPHROSCLEROSIS; DIABETIC-NEPHROPATHY; DEAFNESS DFNB12; MORTALITY RISK; MOUSE MODEL; GENE; PROGRESSION; chronic kidney disease; genome-wide association study; kidney function decline; kidney development; population genetics; single nucleotide polymorphism; zebrafish |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 Jul 2019 13:16 |
| Last Modified: | 19 Jul 2019 13:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5579 |
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