Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine

Schlosser P, Scherer N, Grundner-Culemann F, Monteiro-Martins S, Haug S, Steinbrenner I, Uluvar B, Wuttke M, Cheng Y, Ekici AB, Gyimesi G, Karoly ED, Kotsis F, Mielke J, Gomez MF, Yu B, Grams ME, Coresh J, Boerwinkle E, Köttgen M, Kronenberg F, Meiselbach H, Mohney RP, Akilesh S, Schmidts M, Hediger MA, Schultheiss UT, Eckardt KU, Oefner PJ, Sekula P, Li Y, Köttgen A (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Genetics Nature Publishing Group

DOI: 10.1038/s41588-023-01409-8

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.

Authors with CRIS profile

Arif Bülent Ekici Lehrstuhl für Humangenetik Kai-Uwe Eckardt Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Universität Bern CH Switzerland (CH) Metabolon, Inc. US United States (USA) (US) Bayer AG DE Germany (DE) Lund University / Lunds universitet SE Sweden (SE) University of Texas Health Science Center at Houston (UTHealth) US United States (USA) (US) New York University (NYU) US United States (USA) (US) Johns Hopkins University (JHU) US United States (USA) (US) Medizinische Universität Innsbruck AT Austria (AT) University of Washington US United States (USA) (US) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Universität Regensburg DE Germany (DE)

How to cite

APA:

Schlosser, P., Scherer, N., Grundner-Culemann, F., Monteiro-Martins, S., Haug, S., Steinbrenner, I.,... Köttgen, A. (2023). Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. Nature Genetics. https://doi.org/10.1038/s41588-023-01409-8

MLA:

Schlosser, Pascal, et al. "Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine." Nature Genetics (2023).

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