Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Abstract: 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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Nature communications. - 10 (2019) , 4130, ISSN: 2041-1723
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2019
- Creator
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Teumer, Alexander
Li, Yong
Ghasemi, Sahar
Prins, Bram P.
Wuttke, Matthias
Hermle, Tobias Franz
Hoppmann, Anselm
Gerstner, Lea
Chen, Mengmeng
Grundner-Culemann, Franziska
Butterworth, Adam S.
Hung, Adriana M.
Pattaro, Cristian
Köttgen, Anna
- DOI
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10.1038/s41467-019-11576-0
- URN
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urn:nbn:de:bsz:25-freidok-1509959
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:34 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Teumer, Alexander
- Li, Yong
- Ghasemi, Sahar
- Prins, Bram P.
- Wuttke, Matthias
- Hermle, Tobias Franz
- Hoppmann, Anselm
- Gerstner, Lea
- Chen, Mengmeng
- Grundner-Culemann, Franziska
- Butterworth, Adam S.
- Hung, Adriana M.
- Pattaro, Cristian
- Köttgen, Anna
- Universität
Time of origin
- 2019
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Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
Meta-analyses identify DNA methylation associated with kidney function and damage
Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts
Regional variation in hemoglobin distribution among individuals with CKD: the ISN international network of CKD cohorts
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Zirkulierende Angiopoietin-2- und Tie-2-Konzentrationen in Assoziation zur Nierenfunktion in einer populationsbasierten Studie
Modulation of genetic associations with serum urate levels by body-mass-index in humans
Ammoniakkonzentration in der Ausatemluft bei Patienten vor und nach der Dialyse
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Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
Meta-analyses identify DNA methylation associated with kidney function and damage
Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts
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