Schlosser, Pascal and Li, Yong and Sekula, Peggy and Raffler, Johannes and Grundner-Culemann, Franziska and Pietzner, Maik and Cheng, Yurong and Wuttke, Matthias and Steinbrenner, Inga and Schultheiss, Ulla T. and Kotsis, Fruzsina and Kacprowski, Tim and Forer, Lukas and Hausknecht, Birgit and Ekici, Arif B. and Nauck, Matthias and Voelker, Uwe and Walz, Gerd and Oefner, Peter J. and Kronenberg, Florian and Mohney, Robert P. and Koettgen, Michael and Suhre, Karsten and Eckardt, Kai-Uwe and Kastenmueller, Gabi and Koettgen, Anna (2020) Genetic studies of urinary metabolites illuminate mechanisms of detoxification and excretion in humans. NATURE GENETICS, 52 (2). 167-+. ISSN 1061-4036, 1546-1718
Full text not available from this repository. (Request a copy)Abstract
The kidneys integrate information from continuous systemic processes related to the absorption, distribution, metabolism and excretion (ADME) of metabolites. To identify underlying molecular mechanisms, we performed genome-wide association studies of the urinary concentrations of 1,172 metabolites among 1,627 patients with reduced kidney function. The 240 unique metabolite-locus associations (metabolite quantitative trait loci, mQTLs) that were identified and replicated highlight novel candidate substrates for transport proteins. The identified genes are enriched in ADME-relevant tissues and cell types, and they reveal novel candidates for biotransformation and detoxification reactions. Fine mapping of mQTLs and integration with single-cell gene expression permitted the prioritization of causal genes, functional variants and target cell types. The combination of mQTLs with genetic and health information from 450,000 UK Biobank participants illuminated metabolic mediators, and hence, novel urinary biomarkers of disease risk. This comprehensive resource of genetic targets and their substrates is informative for ADME processes in humans and is relevant to basic science, clinical medicine and pharmaceutical research. Genome-wide association analysis of 1,172 urinary metabolites identifies 240 metabolite-locus associations that when combined with UK Biobank data suggest novel metabolic mediators of disease and markers of disease risk.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; KIDNEY-DISEASE GCKD; UREMIC TOXINS; PACKAGE; METAANALYSIS; TRANSPORTER; EXPRESSION; INSIGHTS; DATASETS; PROFILE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2021 08:12 |
| Last Modified: | 09 Apr 2021 08:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45336 |
Actions (login required)
 |
View Item |
