Title | Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | 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, K-U, Oefner, PJ, Sekula, P, Li, Y, Köttgen, A |
Corporate Authors | GCKD Investigators |
Journal | Nat Genet |
Volume | 55 |
Issue | 6 |
Pagination | 995-1008 |
Date Published | 2023 Jun |
ISSN | 1546-1718 |
Keywords | Kidney, Metabolome, Metabolomics |
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. |
DOI | 10.1038/s41588-023-01409-8 |
Alternate Journal | Nat Genet |
PubMed ID | 37277652 |
PubMed Central ID | PMC10260405 |
Grant List | R01 DK124399 / DK / NIDDK NIH HHS / United States 75N92022D00001 / HL / NHLBI NIH HHS / United States 75N92022D00002 / HL / NHLBI NIH HHS / United States 75N92022D00003 / HL / NHLBI NIH HHS / United States 75N92022D00004 / HL / NHLBI NIH HHS / United States 75N92022D00005 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States R01 HL141824 / HL / NHLBI NIH HHS / United States |
Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.
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