학술논문
Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin
Document Type
Article
Author
Joseph, Christina B.; Mariniello, Marta; Yoshifuji, Ayumi; Schiano, Guglielmo; Lake, Jennifer; Marten, Jonathan; Richmond, Anne; Huffman, Jennifer E.; Campbell, Archie; Harris, Sarah E.; Troyanov, Stephan; Cocca, Massimiliano; Robino, Antonietta; Th?riault, S?bastien; Eckardt, Kai-Uwe; Wuttke, Matthias; Cheng, Yurong; Corre, Tanguy; Kolcic, Ivana; Black, Corrinda; Bruat, Vanessa; Concas, Maria Pina; Sala, Cinzia; Aeschbacher, Stefanie; Schaefer, Franz; Bergmann, Sven; Campbell, Harry; Olden, Matthias; Polasek, Ozren; Porteous, David J.; Deary, Ian J.; Madore, Francois; Awadalla, Philip; Girotto, Giorgia; Ulivi, Sheila; Conen, David; Wuehl, Elke; Olinger, Eric; Wilson, James F.; Bochud, Murielle; K?ttgen, Anna; Hayward, Caroline; Devuyst, Olivier
Source
Journal of the American Society of Nephrology; March 2022, Vol. 33 Issue: 3 p511-529, 19p
Subject
Language
ISSN
10466673; 15333450
Abstract
The mechanisms regulating the urinary excretion of uromodulin remain mostly unknown. A meta-GWAS conducted in 29,315 individuals from 13 cohorts identified two novel, genome-wide significant loci, KRT40and WDR72, in addition to the previously known UMOD-PDILTlocus, to be associated with urinary uromodulin. KRT40 colocalizes with uromodulin in TAL cells and functional studies showed that its expression affects the processing and apical excretion of uromodulin. WDR72, which does not colocalize with uromodulin, has been associated with kidney function, urinary acidification, and kidney stones. These studies provide novel insights into the biology of uromodulin and keratins and into the influence of the UMOD-PDILTlocus on kidney function.