Teumer, Alexander and Li, Yong and Ghasemi, Sahar and Prins, Bram P. and Wuttke, Matthias and Hermle, Tobias and Giri, Ayush and Sieber, Karsten B. and Qiu, Chengxiang and Kirsten, Holger and Tin, Adrienne and Chu, Audrey Y. and Bansal, Nisha and Feitosa, Mary F. and Wang, Lihua and Chai, Jin-Fang and Cocca, Massimiliano and Fuchsberger, Christian and Gorski, Mathias and Hoppmann, Anselm and Horn, Katrin and Li, Man and Marten, Jonathan and Noce, Damia and Nutile, Teresa and Sedaghat, Sanaz and Sveinbjornsson, Gardar and Tayo, Bamidele O. and Van der Most, Peter J. and Xu, Yizhe and Yu, Zhi and Gerstner, Lea and Arnlov, Johan and Bakker, Stephan J. L. and Baptista, Daniela and Biggs, Mary L. and Boerwinkle, Eric and Brenner, Hermann and Burkhardt, Ralph and Carroll, Robert J. and Chee, Miao-Li and Chee, Miao-Ling and Chen, Mengmeng and Cheng, Ching-Yu and Cook, James P. and Coresh, Josef and Corre, Tanguy and Danesh, John and de Borst, Martin H. and De Grandi, Alessandro and de Mutsert, Renee and de Vries, Aiko P. J. and Degenhardt, Frauke and Dittrich, Katalin and Divers, Jasmin and Eckardt, Kai-Uwe and Ehret, Georg and Endlich, Karlhans and Felix, Janine F. and Franco, Oscar H. and Franke, Andre and Freedman, Barry I. and Freitag-Wolf, Sandra and Gansevoort, Ron T. and Giedraitis, Vilmantas and Gogele, Martin and Grundner-Culemann, Franziska and Gudbjartsson, Daniel F. and Gudnason, Vilmundur and Hamet, Pavel and Harris, Tamara B. and Hicks, Andrew A. and Holm, Hilma and Foo, Valencia Hui Xian and Hwang, Shih-Jen and Ikram, M. Arfan and Ingelsson, Erik and Jaddoe, Vincent W. V. and Jakobsdottir, Johanna and Josyula, Navya Shilpa and Jung, Bettina and Kahonen, Mika and Khor, Chiea-Chuen and Kiess, Wieland and Koenig, Wolfgang and Koerner, Antje and Kovacs, Peter and Kramer, Holly and Kraemer, Bernhard K. and Kronenberg, Florian and Lange, Leslie A. and Langefeld, Carl D. and Lee, Jeannette Jen-Mai and Lehtimaki, Terho and Lieb, Wolfgang and Lim, Su-Chi and Lind, Lars and Lindgren, Cecilia M. and Liu, Jianjun and Loeffler, Markus and Lyytikainen, Leo-Pekka and Mahajan, Anubha and Maranville, Joseph C. and Mascalzoni, Deborah and McMullen, Barbara and Meisinger, Christa and Meitinger, Thomas and Miliku, Kozeta and Mook-Kanamori, Dennis O. and Mueller-Nurasyid, Martina and Mychaleckyj, Josyf C. and Nauck, Matthias and Nikus, Kjell and Ning, Boting and Noordam, Raymond and Connell, Jeffrey O' and Olafsson, Isleifur and Palmer, Nicholette D. and Peters, Annette and Podgornaia, Anna I. and Ponte, Belen and Poulain, Tanja and Pramstaller, Peter P. and Rabelink, Ton J. and Raffield, Laura M. and Reilly, Dermot F. and Rettig, Rainer and Rheinberger, Myriam and Rice, Kenneth M. and Rivadeneira, Fernando and Runz, Heiko and Ryan, Kathleen A. and Sabanayagam, Charumathi and Saum, Kai-Uwe and Schoettker, Ben and Shaffer, Christian M. and Shi, Yuan and Smith, Albert V. and Strauch, Konstantin and Stumvoll, Michael and Sun, Benjamin B. and Szymczak, Silke and Tai, E-Shyong and Tan, Nicholas Y. Q. and Taylor, Kent D. and Teren, Andrej and Tham, Yih-Chung and Thiery, Joachim and Thio, Chris H. L. and Thomsen, Hauke and Thorsteinsdottir, Unnur and Tonjes, Anke and Tremblay, Johanne and Uitterlinden, Andre G. and Van der Harst, Pim and Verweij, Niek and Vogelezang, Suzanne and Voelker, Uwe and Waldenberger, Melanie and Wang, Chaolong and Wilson, Otis D. and Wong, Charlene and Wong, Tien-Yin and Yang, Qiong and Yasuda, Masayuki and Akilesh, Shreeram and Bochud, Murielle and Boeger, Carsten A. and Devuyst, Olivier and Edwards, Todd L. and Ho, Kevin and Morris, Andrew P. and Parsa, Afshin and Pendergrass, Sarah A. and Psaty, Bruce M. and Rotter, Jerome I. and Stefansson, Kari and Wilson, James G. and Susztak, Katalin and Snieder, Harold and Heid, Iris M. and Scholz, Markus and Butterworth, Adam S. and Hung, Adriana M. and Pattaro, Cristian and Koettgen, Anna (2019) Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. NATURE COMMUNICATIONS, 10: 4130. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; LD SCORE REGRESSION; KIDNEY-DISEASE; CARDIOVASCULAR EVENTS; COLLABORATIVE METAANALYSIS; BLOOD-PRESSURE; EXCRETION RATE; TRANS-EQTLS; HERITABILITY; RISK; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Apr 2020 09:25 |
| Last Modified: | 06 Apr 2020 09:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26266 |
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