Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Nature Communications | ||||
Verlag: | NATURE PUBLISHING GROUP | ||||
Ort der Veröffentlichung: | LONDON | ||||
Band: | 10 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 1 | ||||
Datum: | 2019 | ||||
Institutionen: | Medizin > Abteilung für Nephrologie Medizin > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medizin > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | GLOMERULAR-FILTRATION-RATE; LD SCORE REGRESSION; KIDNEY-DISEASE; CARDIOVASCULAR EVENTS; COLLABORATIVE METAANALYSIS; BLOOD-PRESSURE; EXCRETION RATE; TRANS-EQTLS; HERITABILITY; RISK; | ||||
Dewey-Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 48260 |
Zusammenfassung
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 ...
Zusammenfassung
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.
Metadaten zuletzt geändert: 03 Sep 2021 09:45