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

Gorski, M.; Tin, A.; Garnaas, M.; McMahon, G.M.; Chu, A.Y.; Tayo, B.O.; Pattaro, C.; Teumer, A.; Chasman, D.I.; Chalmers, J.; Hamet, P.; Tremblay, J.; Woodward, M.; Aspelund, T.; Eiriksdottir, G.; Gudnason, V.; Harris, T.B.; Launer, L.J.; Smith, A.V.; Mitchell, B.D.; O'Connell, J.R.; Shuldiner, A.R.; Coresh, J.; Li, M.; Freudenberger, P.; Hofer, E.; Schmidt, H.; Schmidt, R.; Holliday, E.G.; Mitchell, P.; Wang, J.J.; de Boer, I.H.; Li, G.; Siscovick, D.S.; Kutalik, Z.; Corre, T.; Vollenweider, P.; Waeber, G.; Gupta, J.; Kanetsky, P.A.; Hwang, S.J.; Olden, M.; Yang, Q.; de Andrade, M.; Atkinson, E.J.; Kardia, S.L.; Turner, S.T.; Stafford, J.M.; Ding, J.; Liu, Y.; Barlassina, C.; Cusi, D.; Salvi, E.; Staessen, J.A.; Ridker, P.M.; Grallert, H.; Meisinger, C.; Müller-Nurasyid, M.; Krämer, B.K.; Kramer, H.; Rosas, S.E.; Nolte, I.M.; Penninx, B.W.; Snieder, H.; Fabiola Del Greco, M.; Franke, A.; Nöthlings, U.; Lieb, W.; Bakker, S.J.; Gansevoort, R.T.; van der Harst, P.; Dehghan, A.; Franco, O.H.; Hofman, A.; Rivadeneira, F.; Sedaghat, S.; Uitterlinden, A.G.; 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, J.C.; Metzger, M.; Stengel, B.; Lehtimäki, T.; Lyytikäinen, L.P.; Raitakari, O.; Johnson, A.; Parsa, A.; Bochud, M.; Heid, I.M.; Goessling, W.; Köttgen, A.; Kao, W.H.; Fox, C.S.; Böger, C.A.

doi:10.1038/ki.2014.361

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

Details

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Serval ID

serval:BIB_536FB4F7B8E1

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Kidney International

Author(s)

Gorski M., Tin A., Garnaas M., McMahon G.M., Chu A.Y., Tayo B.O., Pattaro C., Teumer A., Chasman D.I., Chalmers J., Hamet P., Tremblay J., Woodward M., Aspelund T., Eiriksdottir G., Gudnason V., Harris T.B., Launer L.J., Smith A.V., Mitchell B.D., O'Connell J.R., Shuldiner A.R., Coresh J., Li M., Freudenberger P., Hofer E., Schmidt H., Schmidt R., Holliday E.G., Mitchell P., Wang J.J., de Boer I.H., Li G., Siscovick D.S., Kutalik Z., Corre T., Vollenweider P., Waeber G., Gupta J., Kanetsky P.A., Hwang S.J., Olden M., Yang Q., de Andrade M., Atkinson E.J., Kardia S.L., Turner S.T., Stafford J.M., Ding J., Liu Y., Barlassina C., Cusi D., Salvi E., Staessen J.A., Ridker P.M., Grallert H., Meisinger C., Müller-Nurasyid M., Krämer B.K., Kramer H., Rosas S.E., Nolte I.M., Penninx B.W., Snieder H., Fabiola Del Greco M., Franke A., Nöthlings U., Lieb W., Bakker S.J., Gansevoort R.T., van der Harst P., Dehghan A., Franco O.H., Hofman A., Rivadeneira F., Sedaghat S., Uitterlinden A.G., 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 J.C., Metzger M., Stengel B., Lehtimäki T., Lyytikäinen L.P., Raitakari O., Johnson A., Parsa A., Bochud M., Heid I.M., Goessling W., Köttgen A., Kao W.H., Fox C.S., Böger C.A.

ISSN

1523-1755 (Electronic)

ISSN-L

0085-2538

Publication state

Published

Issued date

05/2015

Peer-reviewed

Oui

Volume

Number

Pages

1017-1029

Language

english

Notes

IUMSP2015/05

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 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.

URN

urn:nbn:ch:serval-BIB_536FB4F7B8E17

OAI-PMH

oai:serval.unil.ch:BIB_536FB4F7B8E1

DOI

10.1038/ki.2014.361

Pubmed

25493955

Web of science

000354066900019

Create date

15/12/2014 13:11