Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_6FEAD881CC52
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.
Journal
Nature communications
Author(s)
Teumer A., Li Y., Ghasemi S., Prins B.P., Wuttke M., Hermle T., Giri A., Sieber K.B., Qiu C., Kirsten H., Tin A., Chu A.Y., Bansal N., Feitosa M.F., Wang L., Chai J.F., Cocca M., Fuchsberger C., Gorski M., Hoppmann A., Horn K., Li M., Marten J., Noce D., Nutile T., Sedaghat S., Sveinbjornsson G., Tayo B.O., van der Most P.J., Xu Y., Yu Z., Gerstner L., Ärnlöv J., Bakker SJL, Baptista D., Biggs M.L., Boerwinkle E., Brenner H., Burkhardt R., Carroll R.J., Chee M.L., Chee M.L., Chen M., Cheng C.Y., Cook J.P., Coresh J., Corre T., Danesh J., de Borst M.H., De Grandi A., de Mutsert R., de Vries APJ, Degenhardt F., Dittrich K., Divers J., Eckardt K.U., Ehret G., Endlich K., Felix J.F., Franco O.H., Franke A., Freedman B.I., Freitag-Wolf S., Gansevoort R.T., Giedraitis V., Gögele M., Grundner-Culemann F., Gudbjartsson D.F., Gudnason V., Hamet P., Harris T.B., Hicks A.A., Holm H., Foo VHX, Hwang S.J., Ikram M.A., Ingelsson E., Jaddoe VWV, Jakobsdottir J., Josyula N.S., Jung B., Kähönen M., Khor C.C., Kiess W., Koenig W., Körner A., Kovacs P., Kramer H., Krämer B.K., Kronenberg F., Lange L.A., Langefeld C.D., Lee J.J., Lehtimäki T., Lieb W., Lim S.C., Lind L., Lindgren C.M., Liu J., Loeffler M., Lyytikäinen L.P., Mahajan A., Maranville J.C., Mascalzoni D., McMullen B., Meisinger C., Meitinger T., Miliku K., Mook-Kanamori D.O., Müller-Nurasyid M., Mychaleckyj J.C., Nauck M., Nikus K., Ning B., Noordam R., Connell J.O., Olafsson I., Palmer N.D., Peters A., Podgornaia A.I., Ponte B., Poulain T., Pramstaller P.P., Rabelink T.J., Raffield L.M., Reilly D.F., Rettig R., Rheinberger M., Rice K.M., Rivadeneira F., Runz H., Ryan K.A., Sabanayagam C., Saum K.U., Schöttker B., Shaffer C.M., Shi Y., Smith A.V., Strauch K., Stumvoll M., Sun B.B., Szymczak S., Tai E.S., Tan NYQ, Taylor K.D., Teren A., Tham Y.C., Thiery J., Thio CHL, Thomsen H., Thorsteinsdottir U., Tönjes A., Tremblay J., Uitterlinden A.G., van der Harst P., Verweij N., Vogelezang S., Völker U., Waldenberger M., Wang C., Wilson O.D., Wong C., Wong T.Y., Yang Q., Yasuda M., Akilesh S., Bochud M., Böger C.A., Devuyst O., Edwards T.L., Ho K., Morris A.P., Parsa A., Pendergrass S.A., Psaty B.M., Rotter J.I., Stefansson K., Wilson J.G., Susztak K., Snieder H., Heid I.M., Scholz M., Butterworth A.S., Hung A.M., Pattaro C., Köttgen A.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
11/09/2019
Peer-reviewed
Oui
Volume
10
Number
1
Pages
4130
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2019 16:51
Last modification date
30/04/2021 6:36
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