Genome-wide characterization of 54 urinary metabolites reveals molecular impact of kidney function

Erkka Valo, Anne Richmond, Stefan Mutter, Emma H. Dahlström, Archie Campbell, David J. Porteus, James F. Wilson, Per-Henrik Groop, Caroline Hayward, Niina Sandholm

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

Dissecting the genetic mechanisms underlying urinary metabolite concentrations can provide molecular insights into kidney function and open possibilities for causal assessment of urinary metabolites with risk factors and disease outcomes. Proton nuclear magnetic resonance metabolomics provides a high-throughput means for urinary metabolite profiling, as widely applied for blood biomarker studies. Here we report a genome-wide association study meta-analysed for 3 European cohorts comprising 8,011 individuals, covering both people with type 1 diabetes and general population settings. We identify 54 associations (p < 9.3 x 10(-10)) for 19 of 54 studied metabolite concentrations. Out of these, 33 were not reported previously for relevant urinary or blood metabolite traits. Subsequent two-sample Mendelian randomization analysis suggests that estimated glomerular filtration rate causally affects 13 urinary metabolite concentrations whereas urinary ethanolamine, an initial precursor for phosphatidylcholine and phosphatidylethanolamine, was associated with higher eGFR lending support for a potential protective role. Our study provides a catalogue of genetic associations for 53 metabolites, enabling further investigation on how urinary metabolites are linked to human health.
Alkuperäiskielienglanti
Artikkeli325
LehtiNature Communications
Vuosikerta16
Numero1
Sivumäärä16
ISSN2041-1723
DOI - pysyväislinkit
TilaJulkaistu - 2 tammik. 2025
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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