Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
Show others and affiliations
Number of Authors: 1862019 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 4130Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2019. Vol. 10, article id 4130
National Category
Medical Genetics
Research subject
Health and Welfare
Identifiers
URN: urn:nbn:se:du-30699DOI: 10.1038/s41467-019-11576-0ISI: 000485216900016PubMedID: 31511532Scopus ID: 2-s2.0-85072119437OAI: oai:DiVA.org:du-30699DiVA, id: diva2:1352054
Available from: 2019-09-17 Created: 2019-09-17 Last updated: 2019-09-27Bibliographically approved

Open Access in DiVA

fulltext(9218 kB)23 downloads
File information
File name FULLTEXT01.pdfFile size 9218 kBChecksum SHA-512
bebe0c2cfda49b0904f195d53a9caf18764242877ddd54dacf7fb6b16ee4f33a96ffb6df4569799c96762568b080bbf947b257cf8552de9491905c8d28c4831c
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Ärnlöv, Johan
By organisation
Medical Science
In the same journal
Nature Communications
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 23 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 58 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf