@article{21241, author = {Yang Q. and Wang J. and Chasman D. and Hofman A. and Gudnason V. and Harris T. and Ridker P. and Salvi E. and Kutalik Z. and Bochud M. and Barlassina C. and Staessen J. and Cusi D. and Kao W. and Uitterlinden A. and Kronenberg F. and Stengel B. and Johnson A. and Woodward Mark and Fox C. and Li M. and Lehtimaki T. and Eiriksdottir G. and Gansevoort R. and Hamet P. and Coresh J. and Gorski M. and Tin A. and Garnaas M. and McMahon G. and Chu A. and Tayo B. and Pattaro C. and Teumer A. and Tremblay J. and Aspelund T. and Launer L. and Smith A. and Mitchell B. and O'Connell J. and Shuldiner A. and Freudenberger P. and Hofer E. and Schmidt H. and Schmidt R. and Holliday E. and Mitchell P. and de Boer I. and Li G. and Siscovick D. and Corre T. and Vollenweider P. and Waeber G. and Gupta J. and Kanetsky P. and Hwang S. and Olden M. and de Andrade M. and Atkinson E. and Kardia S. and Turner S. and Stafford J. and Ding J. and Liu Y. and Grallert H. and Meisinger C. and Muller-Nurasyid M. and Kramer B. and Kramer H. and Rosas S. and Nolte I. and Penninx B. and Snieder H. and M. Del Greco Fabiola and Franke A. and Nothlings U. and Lieb W. and Bakker S. and van der Harst P. and Dehghan A. and Franco O. and Rivadeneira F. and Sedaghat S. and Coassin S. and Haun M. and Kollerits B. and Paulweber B. and Aumann N. and Endlich K. and Pietzner M. and Volker U. and Rettig R. and Chouraki V. and Helmer C. and Lambert J. and Metzger M. and Lyytikainen L. and Raitakari O. and Parsa A. and Heid I. and Goessling W. and Kottgen A. and Boger C. and Chalmers J.}, title = {Genome-wide association study of kidney function decline in individuals of European descent: the CKDGen Consortium.}, 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 1.73 m2 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.
}, year = {2015}, journal = {Kidney International}, volume = {87}, edition = {2014/12/11}, pages = {1017-29}, month = {-45793107251}, isbn = {1523-1755 (Electronic)