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Harrer, P. ; Inderhees, J.* ; Zhao, C. ; Schormair, B. ; Tilch, E. ; Gieger, C. ; Peters, A. ; Jöhren, O.* ; Fleming, T.* ; Nawroth, P.P.* ; Berger, K.* ; Hermesdorf, M.* ; Winkelmann, J. ; Schwaninger, M.* ; Oexle, K.

Phenotypic and genome-wide studies on dicarbonyls: Major associations to glomerular filtration rate and gamma-glutamyltransferase activity.

EBioMedicine 101:105007 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: The dicarbonyl compounds methylglyoxal (MG), glyoxal (GO) and 3-deoxyglucosone (3-DG) have been linked to various diseases. However, disease-independent phenotypic and genotypic association studies with phenome-wide and genome-wide reach, respectively, have not been provided. METHODS: MG, GO and 3-DG were measured by LC-MS in 1304 serum samples of two populations (KORA, n = 482; BiDirect, n = 822) and assessed for associations with genome-wide SNPs (GWAS) and with phenome-wide traits. Redundancy analysis (RDA) was used to identify major independent trait associations. FINDINGS: Mutual correlations of dicarbonyls were highly significant, being stronger between MG and GO (ρ = 0.6) than between 3-DG and MG or GO (ρ = 0.4). Significant phenotypic results included associations of all dicarbonyls with sex, waist-to-hip ratio, glomerular filtration rate (GFR), gamma-glutamyltransferase (GGT), and hypertension, of MG and GO with age and C-reactive protein, of GO and 3-DG with glucose and antidiabetics, of MG with contraceptives, of GO with ferritin, and of 3-DG with smoking. RDA revealed GFR, GGT and, in case of 3-DG, glucose as major contributors to dicarbonyl variance. GWAS did not identify genome-wide significant loci. SNPs previously associated with glyoxalase activity did not reach nominal significance. When multiple testing was restricted to the lead SNPs of GWASs on the traits selected by RDA, 3-DG was found to be associated (p = 2.3 × 10-5) with rs1741177, an eQTL of NF-κB inhibitor NFKBIA. INTERPRETATION: This large-scale, population-based study has identified numerous associations, with GFR and GGT being of pivotal importance, providing unbiased perspectives on dicarbonyls beyond the current state. FUNDING: Deutsche Forschungsgemeinschaft, Helmholtz Munich, German Centre for Cardiovascular Research (DZHK), German Federal Ministry of Research and Education (BMBF).
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dicarbonyl Compounds ; Genome-wide Association Study ; Glucose ; Kidney Function ; Liver Enzymes ; Phenotypic Association Study; Genetic Association; Glyoxalase System; Methylglyoxal; Cell; Stress; Identification; Impairs; Stroke; Risk; G5pr
ISSN (print) / ISBN 2352-3964
e-ISSN 2352-3964
Zeitschrift EBioMedicine
Quellenangaben Band: 101, Heft: , Seiten: , Artikelnummer: 105007 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Institute of Epidemiology II (EPI2)
Förderungen German Federal Ministry of Research and Education (BMBF)
German Centre for Cardiovascular Research(DZHK)
Helmholtz Munich
Deutsche Forschungsgemeinschaft