Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Creators: name: Teumer, Alexander
name: Li, Yong
name: Ghasemi, Sahar
name: Prins, Bram P.
name: Wuttke, Matthias
name: Hermle, Tobias
name: Giri, Ayush
name: Sieber, Karsten B.
name: Qiu, Chengxiang
name: Kirsten, Holger
name: Tin, Adrienne
name: Chu, Audrey Y.
name: Bansal, Nisha
name: Feitosa, Mary F.
name: Wang, Lihua
name: Chai, Jin-Fang
name: Cocca, Massimiliano
name: Fuchsberger, Christian
name: Gorski, Mathias
name: Hoppmann, Anselm
name: Horn, Katrin
name: Li, Man
name: Marten, Jonathan
name: Noce, Damia
name: Nutile, Teresa
name: Sedaghat, Sanaz
name: Sveinbjornsson, Gardar
name: Tayo, Bamidele O.
name: Van Der Most, Peter J.
name: Xu, Yizhe
name: Yu, Zhi
name: Gerstner, Lea
name: Ärnlöv, Johan
name: Bakker, Stephan J. L.
name: Baptista, Daniela
name: Biggs, Mary L.
name: Boerwinkle, Eric
name: Brenner, Hermann
name: Burkhardt, Ralph
name: Carroll, Robert J.
name: Chee, Miao-Li
name: Chee, Miao-Ling
name: Chen, Mengmeng
name: Cheng, Ching-Yu
name: Cook, James P.
name: Coresh, Josef
name: Corre, Tanguy
name: Danesh, John
name: De Borst, Martin H.
name: De Grandi, Alessandro
name: De Mutsert, Renée
name: De Vries, Aiko P. J.
name: Degenhardt, Frauke
name: Dittrich, Katalin
name: Divers, Jasmin
name: Eckardt, Kai-Uwe
name: Ehret, Georg
name: Endlich, Karlhans
name: Felix, Janine F.
name: Franco, Oscar H.
name: Franke, Andre
name: Freedman, Barry I.
name: Freitag-Wolf, Sandra
name: Gansevoort, Ron T.
name: Giedraitis, Vilmantas
name: Gögele, Martin
name: Grundner-Culemann, Franziska
name: Gudbjartsson, Daniel F.
name: Gudnason, Vilmundur
name: Hamet, Pavel
name: Harris, Tamara B.
name: Hicks, Andrew A.
name: Holm, Hilma
name: Foo, Valencia Hui Xian
name: Hwang, Shih-Jen
name: Ikram, M. Arfan
name: Ingelsson, Erik
name: Jaddoe, Vincent W. V.
name: Jakobsdottir, Johanna
name: Josyula, Navya Shilpa
name: Jung, Bettina
name: Kähönen, Mika
name: Khor, Chiea-Chuen
name: Kiess, Wieland
name: Koenig, Wolfgang
name: Körner, Antje
name: Kovacs, Peter
name: Kramer, Holly
name: Krämer, Bernhard K.
name: Kronenberg, Florian
name: Lange, Leslie A.
name: Langefeld, Carl D.
name: Lee, Jeannette Jen-Mai
name: Lehtimäki, Terho
name: Lieb, Wolfgang
name: Lim, Su-Chi
name: Lind, Lars
name: Lindgren, Cecilia M.
name: Liu, Jianjun
name: Loeffler, Markus
name: Lyytikäinen, Leo-Pekka
name: Mahajan, Anubha
name: Maranville, Joseph C.
name: Mascalzoni, Deborah
name: McMullen, Barbara
name: Meisinger, Christa
name: Meitinger, Thomas
name: Miliku, Kozeta
name: Mook-Kanamori, Dennis O.
name: Müller-Nurasyid, Martina
name: Mychaleckyj, Josyf C.
name: Nauck, Matthias
name: Nikus, Kjell
name: Ning, Boting
name: Noordam, Raymond
name: Connell, Jeffrey O’
name: Olafsson, Isleifur
name: Palmer, Nicholette D.
name: Peters, Annette
name: Podgornaia, Anna I.
name: Ponte, Belen
name: Poulain, Tanja
name: Pramstaller, Peter P.
name: Rabelink, Ton J.
name: Raffield, Laura M.
name: Reilly, Dermot F.
name: Rettig, Rainer
name: Rheinberger, Myriam
name: Rice, Kenneth M.
name: Rivadeneira, Fernando
name: Runz, Heiko
name: Ryan, Kathleen A.
name: Sabanayagam, Charumathi
name: Saum, Kai-Uwe
name: Schöttker, Ben
name: Shaffer, Christian M.
name: Shi, Yuan
name: Smith, Albert V.
name: Strauch, Konstantin
name: Stumvoll, Michael
name: Sun, Benjamin B.
name: Szymczak, Silke
name: Tai, E-Shyong
name: Tan, Nicholas Y. Q.
name: Taylor, Kent D.
name: Teren, Andrej
name: Tham, Yih-Chung
name: Thiery, Joachim
name: Thio, Chris H. L.
name: Thomsen, Hauke
name: Thorsteinsdottir, Unnur
name: Tönjes, Anke
name: Tremblay, Johanne
name: Uitterlinden, André G.
name: Van Der Harst, Pim
name: Verweij, Niek
name: Vogelezang, Suzanne
name: Völker, Uwe
name: Waldenberger, Melanie
name: Wang, Chaolong
name: Wilson, Otis D.
name: Wong, Charlene
name: Wong, Tien-Yin
name: Yang, Qiong
name: Yasuda, Masayuki
name: Akilesh, Shreeram
name: Bochud, Murielle
name: Böger, Carsten A.
name: Devuyst, Olivier
name: Edwards, Todd L.
name: Ho, Kevin
name: Morris, Andrew P.
name: Parsa, Afshin
name: Pendergrass, Sarah A.
name: Psaty, Bruce M.
name: Rotter, Jerome I.
name: Stefansson, Kari
name: Wilson, James G.
name: Susztak, Katalin
name: Snieder, Harold
name: Heid, Iris M.
name: Scholz, Markus
name: Butterworth, Adam S.
name: Hung, Adriana M.
name: Pattaro, Cristian
name: Köttgen, Anna
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: Article
/631/208/205/2138
/692/4022/1585
/45/43
article

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.