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

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Authors
Teumer, Alexander
Li, Yong
Ghasemi, Sahar
Prins, Bram P
Wuttke, Matthias
Hermle, Tobias
Giri, Ayush
Sieber, Karsten B
Qiu, Chengxiang
Kirsten, Holger
Tin, Adrienne
Chu, Audrey Y
Bansal, Nisha
Feitosa, Mary F
Wang, Lihua
Chai, Jin-Fang
Cocca, Massimiliano
Fuchsberger, Christian
Gorski, Mathias
Hoppmann, Anselm
Horn, Katrin
Li, Man
Marten, Jonathan
Noce, Damia
Nutile, Teresa
Sedaghat, Sanaz
Sveinbjornsson, Gardar
Tayo, Bamidele O
van der Most, Peter J
Xu, Yizhe
Yu, Zhi
Gerstner, Lea
Ärnlöv, Johan
Bakker, Stephan J L
Baptista, Daniela
Biggs, Mary L
Boerwinkle, Eric
Brenner, Hermann
Burkhardt, Ralph
Carroll, Robert J
Chee, Miao-Li
Chee, Miao-Ling
Chen, Mengmeng
Cheng, Ching-Yu
Cook, James P
Coresh, Josef
Corre, Tanguy
Danesh, John
de Borst, Martin H
De Grandi, Alessandro
de Mutsert, Renée
de Vries, Aiko P J
Degenhardt, Frauke
Dittrich, Katalin
Divers, Jasmin
Eckardt, Kai-Uwe
Ehret, Georg
Endlich, Karlhans
Felix, Janine F
Franco, Oscar H
Franke, Andre
Freedman, Barry I
Freitag-Wolf, Sandra
Gansevoort, Ron T
Giedraitis, Vilmantas
Gögele, Martin
Grundner-Culemann, Franziska
Gudbjartsson, Daniel F
Gudnason, Vilmundur
Hamet, Pavel
Harris, Tamara B
Hicks, Andrew A
Holm, Hilma
Foo, Valencia Hui Xian
Hwang, Shih-Jen
Ikram, M Arfan
Ingelsson, Erik
Jaddoe, Vincent W V
Jakobsdottir, Johanna
Josyula, Navya Shilpa
Jung, Bettina
Kähönen, Mika
Khor, Chiea-Chuen
Kiess, Wieland
Koenig, Wolfgang
Körner, Antje
Kovacs, Peter
Kramer, Holly
Krämer, Bernhard K
Kronenberg, Florian
Lange, Leslie A
Langefeld, Carl D
Lee, Jeannette Jen-Mai
Lehtimäki, Terho
Lieb, Wolfgang
Lim, Su-Chi
Lind, Lars
Lindgren, Cecilia M
Liu, Jianjun
Loeffler, Markus
Lyytikäinen, Leo-Pekka
Mahajan, Anubha
Maranville, Joseph C
Mascalzoni, Deborah
McMullen, Barbara
Meisinger, Christa
Meitinger, Thomas
Miliku, Kozeta
Mook-Kanamori, Dennis O
Müller-Nurasyid, Martina
Mychaleckyj, Josyf C
Nauck, Matthias
Nikus, Kjell
Ning, Boting
Noordam, Raymond
Connell, Jeffrey O'
Olafsson, Isleifur
Palmer, Nicholette D
Peters, Annette
Podgornaia, Anna I
Ponte, Belen
Poulain, Tanja
Pramstaller, Peter P
Rabelink, Ton J
Raffield, Laura M
Reilly, Dermot F
Rettig, Rainer
Rheinberger, Myriam
Rice, Kenneth M
Rivadeneira, Fernando
Runz, Heiko
Ryan, Kathleen A
Sabanayagam, Charumathi
Saum, Kai-Uwe
Schöttker, Ben
Shaffer, Christian M
Shi, Yuan
Smith, Albert V
Strauch, Konstantin
Stumvoll, Michael
Sun, Benjamin B
Szymczak, Silke
Tai, E-Shyong
Tan, Nicholas Y Q
Taylor, Kent D
Teren, Andrej
Tham, Yih-Chung
Thiery, Joachim
Thio, Chris H L
Thomsen, Hauke
Thorsteinsdottir, Unnur
Tönjes, Anke
Tremblay, Johanne
Uitterlinden, André G
van der Harst, Pim
Verweij, Niek
Vogelezang, Suzanne
Völker, Uwe
Waldenberger, Melanie
Wang, Chaolong
Wilson, Otis D
Wong, Charlene
Wong, Tien-Yin
Yang, Qiong
Yasuda, Masayuki
Akilesh, Shreeram
Bochud, Murielle
Böger, Carsten A
Devuyst, Olivier
Edwards, Todd L
Ho, Kevin
Morris, Andrew P
Parsa, Afshin
Pendergrass, Sarah A
Psaty, Bruce M
Rotter, Jerome I
Stefansson, Kari
Wilson, James G
Susztak, Katalin
Snieder, Harold
Heid, Iris M
Scholz, Markus
Butterworth, Adam S
Hung, Adriana M
Pattaro, Cristian
Köttgen, Anna
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Útgáfudagur
2019-09-11

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Citation
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. 2019, 10(1):4130 Nat Commun
Útdráttur
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.
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To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download
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https://www.nature.com/articles/s41467-019-11576-0
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739370/
ae974a485f413a2113503eed53cd6c53
10.1038/s41467-019-11576-0
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