Metabolomic profiles predict individual multidisease outcomes
Nature Medicine, vol. 28, pp. 2309–2320
Abstract
Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously.
Authors 32
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Cardiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
Department of Cardiology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
University of Cambridge · Wellcome/MRC Institute of Metabolic Science · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · MRC Epidemiology Unit
Affiliation as printed
Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Computational Medicine, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Leiden University Medical Center
Affiliation as printed
Leiden Computational Biology Center, LUMC, Leiden, The Netherlands
Molecular Epidemiology, LUMC, Leiden, the Netherlands
-
Leiden University Medical Center · Erasmus MC
Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
Center for Digital Health, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Berlin, Germany
-
Affiliation as printed
Institute of Cardiovascular Sciences, University College London, London, UK
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Cardiovascular Research, Charité - Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
Department of Endocrinology & Metabolism, Charité - Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
Department of Endocrinology & Metabolism, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
-
Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Neurology, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany
School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany
-
Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, TU Delft, Delft, the Netherlands
Leiden Computational Biology Center, LUMC, Leiden, The Netherlands
Molecular Epidemiology, LUMC, Leiden, the Netherlands
-
Stella Trompet Aachen Department of Cardiology, Leiden University Medical Center Department of Internal Medicine Division of Gerontology and Geriatrics
Leiden University Medical Center
Affiliation as printed
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Department of Internal Medicine, Division of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
-
Leiden University Medical Center
Affiliation as printed
Department of Internal Medicine, Division of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
-
Affiliation as printed
Institute of Cardiovascular and Medical Sciences, Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
-
Leiden University Medical Center · Netherlands Heart Institute
Affiliation as printed
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
Netherlands Heart Institute, Utrecht, the Netherlands
-
Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Department of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands
-
Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
-
Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
-
Affiliation as printed
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands
-
Leiden University Medical Center · Max Planck Institute for Biology of Ageing
Affiliation as printed
Max Planck Institute for the Biology of Ageing, Cologne, Germany
Molecular Epidemiology, LUMC, Leiden, the Netherlands
-
University of Helsinki · University College London
Affiliation as printed
Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland
Department of Epidemiology and Public Health, University College London, London, UK
-
University of Cambridge · Wellcome/MRC Institute of Metabolic Science · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · MRC Epidemiology Unit
Affiliation as printed
Computational Medicine, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK
-
Affiliation as printed
Institute of Cardiovascular Sciences, University College London, London, UK
-
Roland Eils corresponding
University Hospital Heidelberg · Berlin Institute of Health at Charité - Universitätsmedizin Berlin
Affiliation as printed
Center for Digital Health, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany. roland.eils@bih-charite.de
Health Data Science Unit, Heidelberg University Hospital and BioQuant, Heidelberg, Germany. roland.eils@bih-charite.de
Health Data Science Unit, Heidelberg University Hospital and BioQuant, Heidelberg, Germany
-
Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Cardiology, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
Department of Cardiology, Campus Benjamin Franklin, Charité – Universitätsmedizin Berlin and Berlin Institute of Health, Berlin, Germany
Cited by 392 stored of 399
Cited by patents worldwide 2 (Lens.org)
-
METABOLIC FINGERPRINTING OF SALIVA SAMPLES USING NMRWO2025133394A1 2025-06-26 Pending
-
METHODS FOR PREDICTING COGNITIVE DECLINE IN A SUBJECTWO2025040574A1 2025-02-27 Pending