dc.contributor |
Háskóli Íslands |
dc.contributor |
University of Iceland |
dc.contributor.author |
Teumer, Alexander |
dc.contributor.author |
Li, Yong |
dc.contributor.author |
Ghasemi, Sahar |
dc.contributor.author |
Prins, Bram P. |
dc.contributor.author |
Wuttke, Matthias |
dc.contributor.author |
Hermle, Tobias |
dc.contributor.author |
Giri, Ayush |
dc.contributor.author |
Sieber, Karsten B. |
dc.contributor.author |
Qiu, Chengxiang |
dc.contributor.author |
Kirsten, Holger |
dc.contributor.author |
Tin, Adrienne |
dc.contributor.author |
Chu, Audrey Y. |
dc.contributor.author |
Bansal, Nisha |
dc.contributor.author |
Feitosa, Mary F. |
dc.contributor.author |
Wang, Lihua |
dc.contributor.author |
Chai, Jin-Fang |
dc.contributor.author |
Cocca, Massimiliano |
dc.contributor.author |
Fuchsberger, Christian |
dc.contributor.author |
Gorski, Mathias |
dc.contributor.author |
Hoppmann, Anselm |
dc.contributor.author |
Horn, Katrin |
dc.contributor.author |
Li, Man |
dc.contributor.author |
Marten, Jonathan |
dc.contributor.author |
Noce, Damia |
dc.contributor.author |
Nutile, Teresa |
dc.contributor.author |
Sedaghat, Sanaz |
dc.contributor.author |
Sveinbjornsson, Gardar |
dc.contributor.author |
Tayo, Bamidele O. |
dc.contributor.author |
van der Most, Peter J. |
dc.contributor.author |
Xu, Yizhe |
dc.contributor.author |
Yu, Zhi |
dc.contributor.author |
Gerstner, Lea |
dc.contributor.author |
Ärnlöv, Johan |
dc.contributor.author |
Bakker, Stephan J. L. |
dc.contributor.author |
Baptista, Daniela |
dc.contributor.author |
Biggs, Mary L. |
dc.contributor.author |
Boerwinkle, Eric |
dc.contributor.author |
Brenner, Hermann |
dc.contributor.author |
Burkhardt, Ralph |
dc.contributor.author |
Carroll, Robert J. |
dc.contributor.author |
Chee, Miao-Li |
dc.contributor.author |
Chee, Miao-Ling |
dc.contributor.author |
Chen, Mengmeng |
dc.contributor.author |
Cheng, Ching-Yu |
dc.contributor.author |
Cook, James P. |
dc.contributor.author |
Coresh, Josef |
dc.contributor.author |
Corre, Tanguy |
dc.contributor.author |
Danesh, John |
dc.contributor.author |
de Borst, Martin H. |
dc.contributor.author |
De Grandi, Alessandro |
dc.contributor.author |
de Mutsert, Renée |
dc.contributor.author |
de Vries, Aiko P. J. |
dc.contributor.author |
Degenhardt, Frauke |
dc.contributor.author |
Dittrich, Katalin |
dc.contributor.author |
Divers, Jasmin |
dc.contributor.author |
Eckardt, Kai-Uwe |
dc.contributor.author |
Ehret, Georg |
dc.contributor.author |
Endlich, Karlhans |
dc.contributor.author |
Felix, Janine F. |
dc.contributor.author |
Franco, Oscar H. |
dc.contributor.author |
Franke, Andre |
dc.contributor.author |
Freedman, Barry I. |
dc.contributor.author |
Freitag-Wolf, Sandra |
dc.contributor.author |
Gansevoort, Ron T. |
dc.contributor.author |
Giedraitis, Vilmantas |
dc.contributor.author |
Gögele, Martin |
dc.contributor.author |
Grundner-Culemann, Franziska |
dc.contributor.author |
Gudbjartsson, Daniel |
dc.contributor.author |
Gudnason, Vilmundur |
dc.contributor.author |
Hamet, Pavel |
dc.contributor.author |
Harris, Tamara B. |
dc.contributor.author |
Hicks, Andrew A. |
dc.contributor.author |
Holm, Hilma |
dc.contributor.author |
Foo, Valencia Hui Xian |
dc.contributor.author |
Hwang, Shih-Jen |
dc.contributor.author |
Ikram, M. Arfan |
dc.contributor.author |
Ingelsson, Erik |
dc.contributor.author |
Jaddoe, Vincent W. V. |
dc.contributor.author |
Jakobsdottir, Johanna |
dc.contributor.author |
Josyula, Navya Shilpa |
dc.contributor.author |
Jung, Bettina |
dc.contributor.author |
Kähönen, Mika |
dc.contributor.author |
Khor, Chiea-Chuen |
dc.contributor.author |
Kiess, Wieland |
dc.contributor.author |
Koenig, Wolfgang |
dc.contributor.author |
Körner, Antje |
dc.contributor.author |
Kovacs, Peter |
dc.contributor.author |
Kramer, Holly |
dc.contributor.author |
Krämer, Bernhard K. |
dc.contributor.author |
Kronenberg, Florian |
dc.contributor.author |
Lange, Leslie A. |
dc.contributor.author |
Langefeld, Carl D. |
dc.contributor.author |
Lee, Jeannette Jen-Mai |
dc.contributor.author |
Lehtimäki, Terho |
dc.contributor.author |
Lieb, Wolfgang |
dc.contributor.author |
Lim, Su-Chi |
dc.contributor.author |
Lind, Lars |
dc.contributor.author |
Lindgren, Cecilia M. |
dc.contributor.author |
Liu, Jianjun |
dc.contributor.author |
Loeffler, Markus |
dc.contributor.author |
Lyytikäinen, Leo-Pekka |
dc.contributor.author |
Mahajan, Anubha |
dc.contributor.author |
Maranville, Joseph C. |
dc.contributor.author |
Mascalzoni, Deborah |
dc.contributor.author |
McMullen, Barbara |
dc.contributor.author |
Meisinger, Christa |
dc.contributor.author |
Meitinger, Thomas |
dc.contributor.author |
Miliku, Kozeta |
dc.contributor.author |
Mook-Kanamori, Dennis O. |
dc.contributor.author |
Müller-Nurasyid, Martina |
dc.contributor.author |
Mychaleckyj, Josyf C. |
dc.contributor.author |
Nauck, Matthias |
dc.contributor.author |
Nikus, Kjell |
dc.contributor.author |
Ning, Boting |
dc.contributor.author |
Noordam, Raymond |
dc.contributor.author |
Connell, Jeffrey O’ |
dc.contributor.author |
Olafsson, Isleifur |
dc.contributor.author |
Palmer, Nicholette D. |
dc.contributor.author |
Peters, Annette |
dc.contributor.author |
Podgornaia, Anna I. |
dc.contributor.author |
Ponte, Belen |
dc.contributor.author |
Poulain, Tanja |
dc.contributor.author |
Pramstaller, Peter P. |
dc.contributor.author |
Rabelink, Ton J. |
dc.contributor.author |
Raffield, Laura M. |
dc.contributor.author |
Reilly, Dermot F. |
dc.contributor.author |
Rettig, Rainer |
dc.contributor.author |
Rheinberger, Myriam |
dc.contributor.author |
Rice, Kenneth M. |
dc.contributor.author |
Rivadeneira, Fernando |
dc.contributor.author |
Runz, Heiko |
dc.contributor.author |
Ryan, Kathleen A. |
dc.contributor.author |
Sabanayagam, Charumathi |
dc.contributor.author |
Saum, Kai-Uwe |
dc.contributor.author |
Schöttker, Ben |
dc.contributor.author |
Shaffer, Christian M. |
dc.contributor.author |
Shi, Yuan |
dc.contributor.author |
Smith, Albert Vernon |
dc.contributor.author |
Strauch, Konstantin |
dc.contributor.author |
Stumvoll, Michael |
dc.contributor.author |
Sun, Benjamin B. |
dc.contributor.author |
Szymczak, Silke |
dc.contributor.author |
Tai, E-Shyong |
dc.contributor.author |
Tan, Nicholas Y. Q. |
dc.contributor.author |
Taylor, Kent D. |
dc.contributor.author |
Teren, Andrej |
dc.contributor.author |
Tham, Yih-Chung |
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Thiery, Joachim |
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Thio, Chris H. L. |
dc.contributor.author |
Thomsen, Hauke |
dc.contributor.author |
Thorsteinsdottir, Unnur |
dc.contributor.author |
Tönjes, Anke |
dc.contributor.author |
Tremblay, Johanne |
dc.contributor.author |
Uitterlinden, André G. |
dc.contributor.author |
van der Harst, Pim |
dc.contributor.author |
Verweij, Niek |
dc.contributor.author |
Vogelezang, Suzanne |
dc.contributor.author |
Völker, Uwe |
dc.contributor.author |
Waldenberger, Melanie |
dc.contributor.author |
Wang, Chaolong |
dc.contributor.author |
Wilson, Otis D. |
dc.contributor.author |
Wong, Charlene |
dc.contributor.author |
Wong, Tien-Yin |
dc.contributor.author |
Yang, Qiong |
dc.contributor.author |
Yasuda, Masayuki |
dc.contributor.author |
Akilesh, Shreeram |
dc.contributor.author |
Bochud, Murielle |
dc.contributor.author |
Böger, Carsten A. |
dc.contributor.author |
Devuyst, Olivier |
dc.contributor.author |
Edwards, Todd L. |
dc.contributor.author |
Ho, Kevin |
dc.contributor.author |
Morris, Andrew P. |
dc.contributor.author |
Parsa, Afshin |
dc.contributor.author |
Pendergrass, Sarah A. |
dc.contributor.author |
Psaty, Bruce M. |
dc.contributor.author |
Rotter, Jerome I. |
dc.contributor.author |
Stefansson, Kari |
dc.contributor.author |
Wilson, James G. |
dc.contributor.author |
Susztak, Katalin |
dc.contributor.author |
Snieder, Harold |
dc.contributor.author |
Heid, Iris M. |
dc.contributor.author |
Scholz, Markus |
dc.contributor.author |
Butterworth, Adam S. |
dc.contributor.author |
Hung, Adriana M. |
dc.contributor.author |
Pattaro, Cristian |
dc.contributor.author |
Köttgen, Anna |
dc.date.accessioned |
2020-02-17T13:07:24Z |
dc.date.available |
2020-02-17T13:07:24Z |
dc.date.issued |
2019-09-11 |
dc.identifier.citation |
Teumer, A., Li, Y., Ghasemi, S. et al. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. Nature Communications 10, 4130 (2019). https://doi.org/10.1038/s41467-019-11576-0 |
dc.identifier.issn |
2041-1723 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/1537 |
dc.description |
Publisher's version (útgefin grein). |
dc.description.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. |
dc.description.sponsorship |
Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests. |
dc.format.extent |
4130 |
dc.language.iso |
en |
dc.publisher |
Springer Science and Business Media LLC |
dc.relation.ispartofseries |
Nature Communications;10(1) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Albuminuria |
dc.subject |
Kidney disease |
dc.subject |
Genome-wide association studies |
dc.subject |
Nýrnasjúkdómar |
dc.subject |
Erfðarannsóknir |
dc.title |
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria |
dc.type |
info:eu-repo/semantics/article |
dcterms.license |
Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
dc.description.version |
Peer Reviewed |
dc.identifier.journal |
Nature Communications |
dc.identifier.doi |
10.1038/s41467-019-11576-0 |
dc.contributor.department |
Læknadeild (HÍ) |
dc.contributor.department |
Faculty of Medicine (UI) |
dc.contributor.school |
School of Health Sciences (UI) |
dc.contributor.school |
Heilbrigðisvísindasvið (HÍ) |