UNIGE document Scientific Article
previous document  unige:135505  next document
add to browser collection
Title

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Authors
Teumer, Alexander
Li, Yong
Ghasemi, Sahar
Prins, Bram P
Wuttke, Matthias
Hermle, Tobias
Giri, Ayush
Sieber, Karsten B
show hidden authors show all authors [1 - 186]
Published in Nature Communications. 2019, vol. 10, no. 1, p. 4130
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.
Identifiers
PMID: 31511532
Full text
Structures
Research group Traits génétiques complexes (901)
Citation
(ISO format)
TEUMER, Alexander et al. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria. In: Nature Communications, 2019, vol. 10, n° 1, p. 4130. doi: 10.1038/s41467-019-11576-0 https://archive-ouverte.unige.ch/unige:135505

130 hits

41 downloads

Update

Deposited on : 2020-05-02

Export document
Format :
Citation style :