Genome-wide association study of kidney function decline in individuals of European descent
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Author
Gorski, Mathias
Tin, Adrienne
McMahon, Gearoid M.
Chu, Audrey Y.
Tayo, Bamidele O.
Pattaro, Cristian
Teumer, Alexander
Chasman, Daniel I.
Chalmers, John
Hamet, Pavel
Tremblay, Johanne
Woodward, Marc
Aspelund, Thor
Eiriksdottir, Gudny
Gudnason, Vilmundur
Harris, Tammara B.
Launer, Lenore J.
Smith, Albert V.
Mitchell, Braxton D.
O'Connell, Jeffrey R.
Shuldiner, Alan R.
Coresh, Josef
Li, Man
Freudenberger, Paul
Hofer, Edith
Schmidt, Helena
Schmidt, Reinhold
Holliday, Elizabeth G.
Mitchell, Paul
Wang, Jie Jin
de Boer, Ian H.
Li, Guo
Siscovick, David S.
Kutalik, Zoltan
Corre, Tanguy
Vollenweider, Peter
Waeber, Gérard
Gupta, Jayanta
Kanetsky, Peter A.
Hwang, Shih-Jen
Olden, Matthias
Yang, Qiong
de Andrade, Mariza
Atkinson, Elizabeth J.
Kardia, Sharon L.R.
Turner, Stephen T.
Stafford, Jeanette M.
Ding, Jingzhong
Liu, Yongmei
Barlassina, Cristina
Cusi, Daniele
Salvi, Erika
Staessen, Jan A
Ridker, Paul M
Grallert, Harald
Meisinger, Christa
Müller-Nurasyid, Martina
Krämer, Bernhard K.
Kramer, Holly
Nolte, Ilja M.
Penninx, Brenda W.
Snieder, Harold
Del Greco, Fabiola
Franke, Andre
Nöthlings, Ute
Lieb, Wolfgang
Bakker, Stephan J.L.
Gansevoort, Ron T.
van der Harst, Pim
Dehghan, Abbas
Franco, Oscar H.
Hofman, Albert
Rivadeneira, Fernando
Sedaghat, Sanaz
Uitterlinden, André G.
Coassin, Stefan
Haun, Margot
Kollerits, Barbara
Kronenberg, Florian
Paulweber, Bernhard
Aumann, Nicole
Endlich, Karlhans
Pietzner, Mike
Völker, Uwe
Rettig, Rainer
Chouraki, Vincent
Helmer, Catherine
Lambert, Jean-Charles
Metzger, Marie
Stengel, Benedicte
Lehtimäki, Terho
Lyytikäinen, Leo-Pekka
Raitakari, Olli
Johnson, Andrew
Parsa, Afshin
Bochud, Murielle
Heid, Iris M.
Köttgen, Anna
Kao, H. Linda
Fox, Caroline S.
Böger, Carsten A.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ki.2014.361Metadata
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Gorski, M., A. Tin, M. Garnaas, G. M. McMahon, A. Y. Chu, B. O. Tayo, C. Pattaro, et al. 2014. “Genome-wide association study of kidney function decline in individuals of European descent.” Kidney international 87 (5): 1017-1029. doi:10.1038/ki.2014.361. http://dx.doi.org/10.1038/ki.2014.361.Abstract
Genome wide association studies (GWAS) 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, 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 eGFRdecline of 3ml/min/1.73m2 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 hours after gentamicin treatment compared to 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425568/pdf/Terms of Use
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