Publication Date
6-1-2023
Journal
Nature Genetics
DOI
10.1038/s41588-023-01409-8
PMID
37277652
PMCID
PMC10260405
PubMedCentral® Posted Date
6-5-2023
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Metabolome, Kidney, Metabolomics, Genome-wide association studies, Genomics, Epidemiology, Genetics research, Translational research
Abstract
The kidneys operate at the interface of plasma and urine by clearing molecular waste products while retaining valuable solutes. Genetic studies of paired plasma and urine metabolomes may identify underlying processes. We conducted genome-wide studies of 1,916 plasma and urine metabolites and detected 1,299 significant associations. Associations with 40% of implicated metabolites would have been missed by studying plasma alone. We detected urine-specific findings that provide information about metabolite reabsorption in the kidney, such as aquaporin (AQP)-7-mediated glycerol transport, and different metabolomic footprints of kidney-expressed proteins in plasma and urine that are consistent with their localization and function, including the transporters NaDC3 (SLC13A3) and ASBT (SLC10A2). Shared genetic determinants of 7,073 metabolite-disease combinations represent a resource to better understand metabolic diseases and revealed connections of dipeptidase 1 with circulating digestive enzymes and with hypertension. Extending genetic studies of the metabolome beyond plasma yields unique insights into processes at the interface of body compartments.
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Biochemical Phenomena, Metabolism, and Nutrition Commons, Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Epidemiology Commons, Medical Genetics Commons, Oncology Commons
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