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Plasma metabolites to profile pathways in noncommunicable disease multimorbidity.

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Pietzner, Maik 
Stewart, Isobel D 
Khaw, Kay-Tee 
Michelotti, Gregory A  ORCID logo


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 readout of human physiology to characterize pathways associated with and across 27 incident noncommunicable diseases (NCDs) assessed using electronic health record hospitalization and cancer registry data from over 11,000 participants (219,415 person years). We identified 420 metabolites shared between at least 2 NCDs, representing 65.5% of all 640 significant metabolite-disease associations. We integrated baseline data on over 50 diverse clinical risk factors and characteristics to identify actionable shared pathways represented by those metabolites. Our study highlights liver and kidney function, lipid and glucose metabolism, low-grade inflammation, surrogates of gut microbial diversity and specific health-related behaviors 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.



Aged, Cohort Studies, Female, Humans, Male, Metabolome, Middle Aged, Multimorbidity, Noncommunicable Diseases, Plasma

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Nat Med

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Nature Research


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Medical Research Council (MC_UU_12015/1)
MRC (MC_UU_00006/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
MRC (unknown)
MRC (MC_PC_13048)
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 ( 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).