Metabolomic profiles predict individual multidisease outcomes
Top Cited Papers
Open Access
- 22 September 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 28 (11), 2309-2320
- https://doi.org/10.1038/s41591-022-01980-3
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.Keywords
Funding Information
- Bundesministerium für Bildung und Forschung (01ZZ1802A - 01ZZ1802Z)
- Wellcome Trust (221854/Z/20/Z)
- RCUK | Medical Research Council (MR/R024227/1)
This publication has 64 references indexed in Scilit:
- Prognosis Research Strategy (PROGRESS) 3: Prognostic Model ResearchPLoS Medicine, 2013
- MissForest—non-parametric missing value imputation for mixed-type dataBioinformatics, 2011
- Association of Blood Pressure and Hypertension With the Risk of Parkinson DiseaseHypertension, 2011
- Screening for Albuminuria Identifies Individuals at Increased Renal RiskJournal of the American Society of Nephrology, 2009
- Decision Curve Analysis: A Novel Method for Evaluating Prediction ModelsMedical Decision Making, 2006
- Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity StudyEuropean Journal of Human Genetics, 2005
- Cohort Profile: The Whitehall II studyInternational Journal of Epidemiology, 2005
- Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control studyThe Lancet, 2004
- The design of a prospective study of pravastatin in the elderly at risk (PROSPER)The American Journal of Cardiology, 1999
- Serum Creatinine Concentration and Risk of Cardiovascular DiseaseStroke, 1997