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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Vydáno v:	Nature medicine Ročník 27; číslo 3; s. 471 - 479
Hlavní autoři:	Pietzner, Maik, Stewart, Isobel D., Raffler, Johannes, Khaw, Kay-Tee, Michelotti, Gregory A., Kastenmüller, Gabi, Wareham, Nicholas J., Langenberg, Claudia
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.03.2021 Nature Publishing Group
Témata:	631/114/2164 631/114/2401 631/67 692/499 692/53 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
On-line přístup:	Získat plný text
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 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