An intermediate-effect size variant in UMOD confers risk for chronic kidney disease

Abstract: The genetic architecture of chronic kidney disease (CKD) remains incompletely understood. Variants in the kidney-specific gene UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD) and are associated with kidney function and the risk of CKD in the general population. We identified an intermediate-effect variant, p.Thr62Pro, detected in ∼1/1,000 individuals of European ancestry that showed a high genetic load in familial clusters of CKD and was associated with an odds ratio (OR) of approximately four for kidney failure in the 100,000 Genomes Project and the UK Biobank. Compared with canonical ADTKD mutations, p.Thr62Pro carriers displayed reduced disease severity and an intermediate trafficking defect. These findings complete the spectrum of UMOD-associated kidney diseases and provide a paradigm for the genetic contribution to CKD

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Proceedings of the National Academy of Sciences of the United States of America. - 119, 33 (2022) , e2114734119, ISSN: 1091-6490

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Olinger, Eric ; Schaeffer, Céline ; Cheng, Yurong ; Köttgen, Anna ; Rampoldi, Luca ; Devuyst, Olivier

Further information

• DOI: 10.1073/pnas.2114734119
• URN: urn:nbn:de:bsz:25-freidok-2290877
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:48 PM CET