Plasma metabolites to profile pathways in noncommunicable disease multimorbidity

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 physio...

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Veröffentlicht in:Nature medicine Jg. 27; H. 3; S. 471 - 479
Hauptverfasser: Pietzner, Maik, Stewart, Isobel D., Raffler, Johannes, Khaw, Kay-Tee, Michelotti, Gregory A., Kastenmüller, Gabi, Wareham, Nicholas J., Langenberg, Claudia
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.03.2021
Nature Publishing Group
Schlagworte:
631/114/2164
631/114/2401
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Aged
Biomedical and Life Sciences
Biomedicine
Cancer Research
Chronic conditions
Chronic diseases
Chronic illnesses
Cohort Studies
Comorbidity
Development and progression
Electronic health records
Electronic medical records
Female
Global health
Glucose metabolism
Health aspects
Humans
Identification and classification
Infectious Diseases
Inflammation
Lipid metabolism
Lipids
Male
Metabolic Diseases
Metabolites
Metabolome
Metabolomics
Microorganisms
Middle Aged
Molecular Medicine
Multimorbidity
Neurosciences
Noncommunicable Diseases
Physiological aspects
Plasma - metabolism
Public health
Risk analysis
Risk factors
United Kingdom
ISSN:1078-8956, 1546-170X, 1546-170X
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung: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 ( https://omicscience.org/apps/mwasdisease/ ) to facilitate future research and meta-analyses. Untargeted metabolomics profiling coupled with analysis of electronic health records in over 11,000 participants in the EPIC-Norfolk cohort reveals shared pathways that contribute to multimorbidity of noncommunicable diseases.
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Author contributions
M.P. and C.L. designed the analysis and drafted the manuscript. M.P. and I.D.S. analyzed the data. J.R. and G.K. designed and implemented the web server. K.-T.K. and N.J.W. are principal investigators of the EPIC-Norfolk cohort. G.A.M. advised on metabolite mapping across batches and provided annotations for retired unknown compounds. All authors contributed to the interpretation of the results and critically reviewed the manuscript.
ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/s41591-021-01266-0