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dc.contributor.authorTeumer, Alexanderen_US
dc.contributor.authorQi, Qibinen_US
dc.contributor.authorNethander, Mariaen_US
dc.contributor.authorAschard, Huguesen_US
dc.contributor.authorBandinelli, Stefaniaen_US
dc.contributor.authorBeekman, Marianen_US
dc.contributor.authorBerndt, Sonja I.en_US
dc.contributor.authorBidlingmaier, Martinen_US
dc.contributor.authorBroer, Lindaen_US
dc.contributor.authorCappola, Anneen_US
dc.contributor.authorCeda, Gian Paoloen_US
dc.contributor.authorChanock, Stephenen_US
dc.contributor.authorChen, Ming‐Hueien_US
dc.contributor.authorChen, Tai C.en_US
dc.contributor.authorChen, Yii‐Der Idaen_US
dc.contributor.authorChung, Jonathanen_US
dc.contributor.authorDel Greco Miglianico, Fabiolaen_US
dc.contributor.authorEriksson, Joelen_US
dc.contributor.authorFerrucci, Luigien_US
dc.contributor.authorFriedrich, Neleen_US
dc.contributor.authorGnewuch, Carstenen_US
dc.contributor.authorGoodarzi, Mark O.en_US
dc.contributor.authorGrarup, Nielsen_US
dc.contributor.authorGuo, Tingweien_US
dc.contributor.authorHammer, Elkeen_US
dc.contributor.authorHayes, Richard B.en_US
dc.contributor.authorHicks, Andrew A.en_US
dc.contributor.authorHofman, Alberten_US
dc.contributor.authorHouwing‐Duistermaat, Jeanine J.en_US
dc.contributor.authorHu, Franken_US
dc.contributor.authorHunter, David J.en_US
dc.contributor.authorHusemoen, Lise L.en_US
dc.contributor.authorIsaacs, Aaronen_US
dc.contributor.authorJacobs, Kevin B.en_US
dc.contributor.authorJanssen, Joop A. M. J. L.en_US
dc.contributor.authorJansson, John‐Oloven_US
dc.contributor.authorJehmlich, Nicoen_US
dc.contributor.authorJohnson, Simonen_US
dc.contributor.authorJuul, Andersen_US
dc.contributor.authorKarlsson, Magnusen_US
dc.contributor.authorKilpelainen, Tuomas O.en_US
dc.contributor.authorKovacs, Peteren_US
dc.contributor.authorKraft, Peteren_US
dc.contributor.authorLi, Chaoen_US
dc.contributor.authorLinneberg, Allanen_US
dc.contributor.authorLiu, Yongmeien_US
dc.contributor.authorLoos, Ruth J. F.en_US
dc.contributor.authorLorentzon, Mattiasen_US
dc.contributor.authorLu, Yingchangen_US
dc.contributor.authorMaggio, Marcelloen_US
dc.contributor.authorMagi, Reediken_US
dc.contributor.authorMeigs, Jamesen_US
dc.contributor.authorMellström, Danen_US
dc.contributor.authorNauck, Matthiasen_US
dc.contributor.authorNewman, Anne B.en_US
dc.contributor.authorPollak, Michael N.en_US
dc.contributor.authorPramstaller, Peter P.en_US
dc.contributor.authorProkopenko, Ingaen_US
dc.contributor.authorPsaty, Bruce M.en_US
dc.contributor.authorReincke, Martinen_US
dc.contributor.authorRimm, Eric B.en_US
dc.contributor.authorRotter, Jerome I.en_US
dc.contributor.authorSaint Pierre, Audeen_US
dc.contributor.authorSchurmann, Claudiaen_US
dc.contributor.authorSeshadri, Sudhaen_US
dc.contributor.authorSjögren, Klaraen_US
dc.contributor.authorSlagboom, P. Elineen_US
dc.contributor.authorStrickler, Howard D.en_US
dc.contributor.authorStumvoll, Michaelen_US
dc.contributor.authorSuh, Yousinen_US
dc.contributor.authorSun, Qien_US
dc.contributor.authorZhang, Cuilinen_US
dc.contributor.authorSvensson, Johanen_US
dc.contributor.authorTanaka, Toshikoen_US
dc.contributor.authorTare, Archanaen_US
dc.contributor.authorTönjes, Ankeen_US
dc.contributor.authorUh, Hae‐Wonen_US
dc.contributor.authorvan Duijn, Cornelia M.en_US
dc.contributor.authorvan Heemst, Dianaen_US
dc.contributor.authorVandenput, Liesbethen_US
dc.contributor.authorVasan, Ramachandran S.en_US
dc.contributor.authorVölker, Uween_US
dc.contributor.authorWillems, Sara M.en_US
dc.contributor.authorOhlsson, Claesen_US
dc.contributor.authorWallaschofski, Henrien_US
dc.contributor.authorKaplan, Robert C.en_US
dc.date.accessioned2016-11-18T20:48:43Z
dc.date.issued2016en_US
dc.identifier.citationTeumer, A., Q. Qi, M. Nethander, H. Aschard, S. Bandinelli, M. Beekman, S. I. Berndt, et al. 2016. “Genomewide meta‐analysis identifies loci associated with IGF‐I and IGFBP‐3 levels with impact on age‐related traits.” Aging Cell 15 (5): 811-824. doi:10.1111/acel.12490. http://dx.doi.org/10.1111/acel.12490.en
dc.identifier.issn1474-9718en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29408427
dc.description.abstractSummary The growth hormone/insulin‐like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF‐related proteins including IGF‐I and IGF‐binding protein‐3 (IGFBP‐3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30 884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF‐I and IGFBP‐3 concentrations (IGF1, IGFBP3,GCKR,TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype–phenotype associations between men and women, were found only for associations of IGFBP‐3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF‐I and IGFBP‐3 concentrations. The IGF‐I‐decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90 years. The known longevity‐associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF‐I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF‐I‐ and IGFBP‐3‐associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF‐I and IGFBP‐3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity‐associated loci.en
dc.language.isoen_USen
dc.publisherJohn Wiley and Sons Inc.en
dc.relation.isversionofdoi:10.1111/acel.12490en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013013/pdf/en
dash.licenseLAAen_US
dc.subjectOriginal Articleen
dc.subjectagingen
dc.subjectgenomewide association studyen
dc.subjectgrowth hormone axisen
dc.subjectlongevityen
dc.titleGenomewide meta‐analysis identifies loci associated with IGF‐I and IGFBP‐3 levels with impact on age‐related traitsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalAging Cellen
dash.depositing.authorAschard, Huguesen_US
dc.date.available2016-11-18T20:48:43Z
dc.identifier.doi10.1111/acel.12490*
dash.authorsorderedfalse
dash.contributor.affiliatedHu, Frank
dash.contributor.affiliatedKraft, Phillip
dash.contributor.affiliatedHunter, David
dash.contributor.affiliatedAschard, Hugues
dash.contributor.affiliatedSun, Qi
dash.contributor.affiliatedRimm, Eric
dash.contributor.affiliatedMeigs, James


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