Genome-wide association study of kidney function decline in individuals of European descent.

TitleGenome-wide association study of kidney function decline in individuals of European descent.
Publication TypeJournal Article
Year of Publication2015
AuthorsGorski, M, Tin, A, Garnaas, M, McMahon, GM, Chu, AY, Tayo, BO, Pattaro, C, Teumer, A, Chasman, DI, Chalmers, J, Hamet, P, Tremblay, J, Woodward, M, Aspelund, T, Eiriksdottir, G, Gudnason, V, Harris, TB, Launer, LJ, Smith, AV, Mitchell, BD, O'Connell, JR, Shuldiner, AR, Coresh, J, Li, M, Freudenberger, P, Hofer, E, Schmidt, H, Schmidt, R, Holliday, EG, Mitchell, P, Wang, JJ, de Boer, IH, Li, G, Siscovick, DS, Kutalik, Z, Corre, T, Vollenweider, P, Waeber, G, Gupta, J, Kanetsky, PA, Hwang, SJ, Olden, M, Yang, Q, de Andrade, M, Atkinson, EJ, Kardia, SL, Turner, ST, Stafford, JM, Ding, J, Liu, Y, Barlassina, C, Cusi, D, Salvi, E, Staessen, JA, Ridker, PM, Grallert, H, Meisinger, C, Müller-Nurasyid, M, Krämer, BK, Kramer, H, Rosas, SE, Nolte, IM, Penninx, BW, Snieder, H, M. Del Greco, F, Franke, A, Nöthlings, U, Lieb, W, Bakker, SJL, Gansevoort, RT, van der Harst, P, Dehghan, A, Franco, OH, Hofman, A, Rivadeneira, F, Sedaghat, S, Uitterlinden, AG, Coassin, S, Haun, M, Kollerits, B, Kronenberg, F, Paulweber, B, Aumann, N, Endlich, K, Pietzner, M, Völker, U, Rettig, R, Chouraki, V, Helmer, C, Lambert, JC, Metzger, M, Stengel, B, Lehtimäki, T, Lyytikäinen, LP, Raitakari, O, Johnson, A, Parsa, A, Bochud, M, Heid, IM, Goessling, W, Köttgen, A, Kao, WH, Fox, CS, Böger, CA
JournalKidney International
Date Published05/2015

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 1.73 m(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.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361.



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Alternate JournalKidney Int.
Citation Key / SERVAL IDserval:BIB_536FB4F7B8E1
Peer reviewRefereed
PubMed ID25493955
PubMed Central IDPMC4425568
Grant ListR01 AG018728 / AG / NIA NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States


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