Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.
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Pietzner, M., Stewart, I., Raffler, J., Khaw, K., Michelotti, G. A., Kastenmüller, G., Wareham, N., & et al. (2021). Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.. Nature medicine, 27 (3), 471-479. https://doi.org/10.1038/s41591-021-01266-0
Multimorbidity, the simultaneous presence of multiple chronic conditions, is an increasing global health problem and research into its determinants is of high priority. We used baseline untargeted plasma metabolomics profiling covering >1,000 metabolites as a comprehensive read out of human physiology to characterise pathways associated across 27 incident non-communicable diseases (NCDs) assessed using electronic health record hospitalisation and cancer registry data from over 11,000 participants (219,415 person-years). We identified two-thirds of the pathways to be shared among the diseases. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways and highlight the importance of liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity, and specific health-related behaviours as antecedents of common NCD multimorbidity with potential for early prevention. We integrated results into an open-access webserver to facilitate future research and meta-analyses.
Plasma, Humans, Cohort Studies, Aged, Middle Aged, Female, Male, Metabolome, Noncommunicable Diseases, Multimorbidity
We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. The EPIC-Norfolk study (https://doi.org/10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK (C864/A14136). Metabolite measurements in the EPIC-Norfolk study were supported by the MRC Cambridge Initiative in Metabolic Science (MR/L00002/1) and the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement no. 115372. MP was supported by a fellowship of the German Research Foundation (DFG 1446/2-1). JR is supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (grant no. 01ZX1912D).
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
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External DOI: https://doi.org/10.1038/s41591-021-01266-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/312895
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