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dc.contributor.authorGomez-Cabrero, David
dc.contributor.authoron behalf of the FRAILOMIC initiative
dc.contributor.authorWalter, Stefan
dc.contributor.authorAbugessaisa, Imad
dc.contributor.authorMiñambres-Herraiz, Rebeca
dc.contributor.authorPalomares, Lucia Bernad
dc.contributor.authorButcher, Lee
dc.contributor.authorErusalimsky, Jorge D.
dc.contributor.authorGarcia-Garcia, Francisco Jose
dc.contributor.authorCarnicero, José
dc.contributor.authorHardman, Timothy C.
dc.contributor.authorMischak, Harald
dc.contributor.authorZürbig, Petra
dc.contributor.authorHackl, Matthias
dc.contributor.authorGrillari, Johannes
dc.contributor.authorFiorillo, Edoardo
dc.contributor.authorCucca, Francesco
dc.contributor.authorCesari, Matteo
dc.contributor.authorCarrie, Isabelle
dc.contributor.authorColpo, Marco
dc.contributor.authorBandinelli, Stefania
dc.contributor.authorFeart, Catherine
dc.contributor.authorPeres, Karine
dc.contributor.authorDartigues, Jean-François
dc.contributor.authorHelmer, Catherine
dc.contributor.authorViña, José
dc.contributor.authorOlaso, Gloria
dc.contributor.authorGarcía-Palmero, Irene
dc.contributor.authorMartínez, Jorge García
dc.contributor.authorJansen-Dürr, Pidder
dc.contributor.authorGrune, Tilman
dc.contributor.authorWeber, Daniela
dc.contributor.authorLippi, Giuseppe
dc.contributor.authorBonaguri, Chiara
dc.contributor.authorSinclair, Alan J
dc.contributor.authorTegner, Jesper
dc.contributor.authorRodriguez-Mañas, Leocadio
dc.date.accessioned2021-02-21T11:11:07Z
dc.date.available2021-02-21T11:11:07Z
dc.date.issued2021-02-18
dc.date.submitted2020-10-06
dc.identifier.citationGomez-Cabrero, D., Walter, S., Abugessaisa, I., Miñambres-Herraiz, R., Palomares, L. B., … Rodriguez-Mañas, L. (2021). A robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts. GeroScience. doi:10.1007/s11357-021-00334-0
dc.identifier.issn2509-2715
dc.identifier.issn2509-2723
dc.identifier.pmid33599920
dc.identifier.doi10.1007/s11357-021-00334-0
dc.identifier.urihttp://hdl.handle.net/10754/667522
dc.description.abstractPhenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68-0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70-0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56-0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23-1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81-0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27-1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21-1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01-1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability.
dc.description.sponsorshipThis work was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013) FRAILOMIC Project (grant number 305483). The Three-City Study was conducted under a partnership agreement between the Institut National de la Santé et de la Recherche Médicale, Victor Segalen – Bordeaux2 University and the Sanofi-Synthélabo company. The Fondation pour la Recherche Médicale funded the preparation and beginning of the study. The 3C-Study was also sponsored by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, Ministry of Research-INSERM Program Cohortes et collections de données biologiques, the Fondation Plan Alzheimer (FCS 2009-2012), and the Caisse Nationale pour la Solidarité et l’Autonomie. The InCHIANTI study baseline (1998–2000) was supported as a ‘targeted project’ (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336) and by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland.Data AvailabilityData will be made freely available
dc.publisherSpringer Nature
dc.relation.urlhttp://link.springer.com/10.1007/s11357-021-00334-0
dc.rightsArchived with thanks to GeroScience
dc.titleA robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalGeroScience
dc.rights.embargodate2022-02-18
dc.eprint.versionPost-print
kaust.personTegner, Jesper
dc.date.accepted2021-02-02


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