title: Identification and MS-assisted interpretation of genetically influenced NMR signals in human plasma.
abstract: Nuclear magnetic resonance spectroscopy (NMR) provides robust readouts of many metabolic parameters in one experiment. However, identification of clinically relevant markers in (1)H NMR spectra is a major challenge. Association of NMR-derived quantities with genetic variants can uncover biologically relevant metabolic traits. Using NMR data of plasma samples from 1,757 individuals from the KORA study together with 655,658 genetic variants, we show that ratios between NMR intensities at two chemical shift positions can provide informative and robust biomarkers. We report seven loci of genetic association with NMR-derived traits (APOA1, CETP, CPS1, GCKR, FADS1, LIPC, PYROXD2) and characterize these traits biochemically using mass spectrometry. These ratios may now be used in clinical studies.
authors: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany ; Faculty of Biology, Ludwig-Maximilians-Universität, Großhaderner Straße 2, 82152 Planegg-Martinsried, Germany.
authors: Johannes
authors: J
authors: Raffler
authors: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Werner
authors: W
authors: Römisch-Margl
authors: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Ann-Kristin
authors: AK
authors: Petersen
authors: numares GmbH, Josef-Engert-Str. 9, 93053 Regensburg, Germany.
authors: Philipp
authors: P
authors: Pagel
authors: numares GmbH, Josef-Engert-Str. 9, 93053 Regensburg, Germany.
authors: Florian
authors: F
authors: Blöchl
authors: Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Germany.
authors: Christian
authors: C
authors: Hengstenberg
authors: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany ; Hannover Unified Biobank, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
authors: Thomas
authors: T
authors: Illig
authors: Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Christa
authors: C
authors: Meisinger
authors: Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Germany ; Department of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Germany.
authors: Klaus
authors: K
authors: Stark
authors: Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: H-Erich
authors: HE
authors: Wichmann
authors: Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Jerzy
authors: J
authors: Adamski
authors: Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Christian
authors: C
authors: Gieger
authors: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany.
authors: Gabi
authors: G
authors: Kastenmüller
authors: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany ; Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, P.O. BOX 24144, Doha, Qatar.
authors: Karsten
authors: K
authors: Suhre