Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/28122
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dc.contributor.authorTimmons, James Aen_UK
dc.contributor.authorKnudsen, Steenen_UK
dc.contributor.authorRankinen, Tuomoen_UK
dc.contributor.authorKoch, Lauren Gen_UK
dc.contributor.authorSarzynski, Mark Aen_UK
dc.contributor.authorJensen, Thomasen_UK
dc.contributor.authorKeller, Pernilleen_UK
dc.contributor.authorScheele, Camillaen_UK
dc.contributor.authorVollaard, Nielsen_UK
dc.contributor.authorNielsen, Sørenen_UK
dc.contributor.authorAkerström, Thorbjörnen_UK
dc.contributor.authorMacDougald, Ormond Aen_UK
dc.contributor.authorJansson, Evaen_UK
dc.contributor.authorGreenhaff, Paul Len_UK
dc.contributor.authorTarnopolsky, Mark Aen_UK
dc.date.accessioned2018-11-08T15:37:44Z-
dc.date.available2018-11-08T15:37:44Z-
dc.date.issued2010-06-30en_UK
dc.identifier.urihttp://hdl.handle.net/1893/28122-
dc.description.abstractA low maximal oxygen consumption (Vo2max is a strong risk factor for premature mortality. Supervised endurance exercise training increases Vo2max with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression, profiling to produce a molecular classifier that predicts Vo2max training response. We then, hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous Vo2max response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA. expression signature that predicted change in Vo2max ("predictor" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted V̇o2max training response on a continuous scale; these genes contained ∼6 new single-nucleotide polymorphisms associated with gains in Vo2max in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., "reciprocal" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in Vo2max, corresponding to ∼50% of the estimated genetic variance for Vo2max. In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. Vo2max responses to endurance training can be predicted by measuring a ∼30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans. en_UK
dc.language.isoenen_UK
dc.publisherAmerican Physiological Societyen_UK
dc.relationTimmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski MA, Jensen T, Keller P, Scheele C, Vollaard N, Nielsen S, Akerström T, MacDougald OA, Jansson E, Greenhaff PL & Tarnopolsky MA (2010) Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. Journal of Applied Physiology, 108 (6), pp. 1487-1496. https://doi.org/10.1152/japplphysiol.01295.2009en_UK
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.en_UK
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_UK
dc.subjectendurance trainingen_UK
dc.subjectgenotypeen_UK
dc.subjectpersonalized medicineen_UK
dc.titleUsing molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humansen_UK
dc.typeJournal Articleen_UK
dc.rights.embargodate2999-12-31en_UK
dc.rights.embargoreason[Vollaard_Journal_of_Applied_Physiology_2010.pdf] The publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.en_UK
dc.identifier.doi10.1152/japplphysiol.01295.2009en_UK
dc.identifier.pmid20133430en_UK
dc.citation.jtitleJournal of Applied Physiologyen_UK
dc.citation.issn1522-1601en_UK
dc.citation.issn8750-7587en_UK
dc.citation.volume108en_UK
dc.citation.issue6en_UK
dc.citation.spage1487en_UK
dc.citation.epage1496en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.funderThe Wellcome Trusten_UK
dc.author.emailn.vollaard@stir.ac.uken_UK
dc.description.notesAdditional Co-Authors: Luc J C van Loon, Bente K Pedersen, Carl Johan Sundberg, Claes Wahlestedt, Steven L Britton, and Claude Boucharden_UK
dc.contributor.affiliationUniversity of Copenhagenen_UK
dc.contributor.affiliationMedical Prognosis Institute A/Sen_UK
dc.contributor.affiliationPennington Biomedical Research Centeren_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationPennington Biomedical Research Centeren_UK
dc.contributor.affiliationMedical Prognosis Institute A/Sen_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationStockholm Universityen_UK
dc.contributor.affiliationUniversity of Maastrichten_UK
dc.contributor.affiliationUniversity of Copenhagenen_UK
dc.contributor.affiliationUniversity of Copenhagenen_UK
dc.contributor.affiliationUniversity of Michiganen_UK
dc.contributor.affiliationKarolinska University Hospitalen_UK
dc.contributor.affiliationUniversity of Nottinghamen_UK
dc.contributor.affiliationMcMaster Universityen_UK
dc.identifier.isiWOS:000279280100010en_UK
dc.identifier.scopusid2-s2.0-77953164300en_UK
dc.identifier.wtid546369en_UK
dc.contributor.orcid0000-0002-4576-8879en_UK
dc.date.accepted2010-01-14en_UK
dcterms.dateAccepted2010-01-14en_UK
dc.date.filedepositdate2018-11-06en_UK
rioxxterms.apcnot requireden_UK
rioxxterms.typeJournal Article/Reviewen_UK
rioxxterms.versionVoRen_UK
local.rioxx.authorTimmons, James A|en_UK
local.rioxx.authorKnudsen, Steen|en_UK
local.rioxx.authorRankinen, Tuomo|en_UK
local.rioxx.authorKoch, Lauren G|en_UK
local.rioxx.authorSarzynski, Mark A|en_UK
local.rioxx.authorJensen, Thomas|en_UK
local.rioxx.authorKeller, Pernille|en_UK
local.rioxx.authorScheele, Camilla|en_UK
local.rioxx.authorVollaard, Niels|0000-0002-4576-8879en_UK
local.rioxx.authorNielsen, Søren|en_UK
local.rioxx.authorAkerström, Thorbjörn|en_UK
local.rioxx.authorMacDougald, Ormond A|en_UK
local.rioxx.authorJansson, Eva|en_UK
local.rioxx.authorGreenhaff, Paul L|en_UK
local.rioxx.authorTarnopolsky, Mark A|en_UK
local.rioxx.projectProject ID unknown|The Wellcome Trust|en_UK
local.rioxx.freetoreaddate2260-05-31en_UK
local.rioxx.licencehttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved||en_UK
local.rioxx.filenameVollaard_Journal_of_Applied_Physiology_2010.pdfen_UK
local.rioxx.filecount1en_UK
local.rioxx.source8750-7587en_UK
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