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dc.contributor.authorPietzner, Maiken
dc.contributor.authorStewart, Isobelen
dc.contributor.authorRaffler, Johannesen
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorMichelotti, Gregory Aen
dc.contributor.authorKastenmüller, Gabien
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorLangenberg, Claudiaen
dc.date.accessioned2020-11-14T00:30:38Z
dc.date.available2020-11-14T00:30:38Z
dc.date.issued2021-03-11en
dc.identifier.issn1078-8956
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/312895
dc.description.abstractMultimorbidity, 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.
dc.description.sponsorshipWe 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).
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherNature Research
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectPlasmaen
dc.subjectHumansen
dc.subjectCohort Studiesen
dc.subjectAgeden
dc.subjectMiddle Ageden
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectMetabolomeen
dc.subjectNoncommunicable Diseasesen
dc.subjectMultimorbidityen
dc.titlePlasma metabolites to profile pathways in noncommunicable disease multimorbidity.en
dc.typeArticle
prism.endingPage479
prism.issueIdentifier3en
prism.publicationDate2021en
prism.publicationNameNature medicineen
prism.startingPage471
prism.volume27en
dc.identifier.doi10.17863/CAM.59992
dcterms.dateAccepted2021-01-27en
rioxxterms.versionofrecord10.1038/s41591-021-01266-0en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-03-11en
dc.contributor.orcidRaffler, Johannes [0000-0003-2495-4020]
dc.contributor.orcidMichelotti, Gregory A [0000-0002-3936-4675]
dc.contributor.orcidKastenmüller, Gabi [0000-0002-2368-7322]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.identifier.eissn1546-170X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idMRC (MC_UU_00006/1)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
cam.orpheus.successMon Mar 22 07:32:12 GMT 2021 - Embargo updated*
cam.orpheus.counter19*
rioxxterms.freetoread.startdate2021-09-11


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