A catalog of genetic loci associated with kidney function from analyses of a million individuals

• Verfasst von: Wuttke, Matthias [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Delgado Gonzales de Kleber, Graciela [VerfasserIn]
• Verfasst von: Jonas, Jost B. [VerfasserIn]
• Verfasst von: Kleber, Marcus E. [VerfasserIn]
• Verfasst von: Krämer, Bernhard [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Verfasst von: Schöttker, Ben [VerfasserIn]
• Titel: A catalog of genetic loci associated with kidney function from analyses of a million individuals
• Verf.angabe: Matthias Wuttke, Hermann Brenner, Graciela Delgado, Jost B. Jonas, Marcus E. Kleber, Bernhard K. Krämer, Winfried März, Ben Schöttker [und 321 weitere]
• Jahr: 2019
• Umfang: 16 S.
• Fussnoten: Gesehen am 19.06.2019
• Titel Quelle: Enthalten in: Nature genetics
• Ort Quelle: London : Macmillan Publishers Limited, part of Springer Nature, 1992
• Jahr Quelle: 2019
• Band/Heft Quelle: 51(2019), 6, Seite 957-972
• ISSN Quelle: 1546-1718
• DOI: doi:10.1038/s41588-019-0407-x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 166765974X

Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.