Dokumentenart: | Artikel | ||||
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Titel eines Journals oder einer Zeitschrift: | Nature Genetics | ||||
Verlag: | Nature | ||||
Ort der Veröffentlichung: | NEW YORK | ||||
Band: | 51 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 6 | ||||
Seitenbereich: | S. 957-972 | ||||
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: | GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RENAL-FUNCTION; TRANS-EQTLS; DISEASE; METAANALYSIS; TRANSPORTER; CLASSIFICATION; HERITABILITY; INTEGRATION; | ||||
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: | 48625 |
Zusammenfassung
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry 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 ...
Zusammenfassung
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry 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.
Metadaten zuletzt geändert: 03 Sep 2021 10:01