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

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.

doi:10.1038/s41467-019-11576-0

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

Details

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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

UNIL/CHUV

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

Number

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.

OAI-PMH

oai:serval.unil.ch:BIB_6FEAD881CC52

DOI

10.1038/s41467-019-11576-0

Pubmed

31511532

Web of science

000485216900016

Open Access

Yes

Create date

01/11/2019 16:51