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dc.contributor.authorTeumer A
dc.contributor.authorQi Q
dc.contributor.authorNethander M
dc.contributor.authorAschard H
dc.contributor.authorBandinelli S
dc.contributor.authorBeekman M
dc.contributor.authorBerndt SI
dc.contributor.authorBidlingmaier M
dc.contributor.authorBroer L
dc.contributor.authorCHARGE Longevity Working Group
dc.contributor.authorCappola A
dc.contributor.authorCeda GP
dc.contributor.authorChanock S
dc.contributor.authorChen MH
dc.contributor.authorChen TC
dc.contributor.authorChen YD
dc.contributor.authorChung J
dc.contributor.authorDel Greco M F
dc.contributor.authorEriksson J
dc.contributor.authorFerrucci L
dc.contributor.authorFriedrich N
dc.contributor.authorGnewuch C
dc.contributor.authorGoodarzi MO
dc.contributor.authorGrarup N
dc.contributor.authorGuo T
dc.contributor.authorHammer E
dc.contributor.authorHayes RB
dc.contributor.authorHicks AA
dc.contributor.authorHofman A
dc.contributor.authorHouwing-Duistermaat JJ
dc.contributor.authorHu F
dc.contributor.authorHunter DJ
dc.contributor.authorHusemoen LL
dc.contributor.authorIsaacs A
dc.contributor.authorJacobs KB
dc.contributor.authorJanssen JA
dc.contributor.authorJansson JO
dc.contributor.authorJehmlich N
dc.contributor.authorJohnson S
dc.contributor.authorJuul A
dc.contributor.authorKarlsson M
dc.contributor.authorKilpelainen TO
dc.contributor.authorKovacs P
dc.contributor.authorKraft P
dc.contributor.authorLi C
dc.contributor.authorLinneberg A
dc.contributor.authorLiu Y
dc.contributor.authorLoos RJ
dc.contributor.authorBody Composition Genetics Consortium
dc.contributor.authorLorentzon M
dc.contributor.authorLu Y
dc.contributor.authorMaggio M
dc.contributor.authorMagi R
dc.contributor.authorMeigs J
dc.contributor.authorMellström D
dc.contributor.authorNauck M
dc.contributor.authorNewman AB
dc.contributor.authorPollak MN
dc.contributor.authorPramstaller PP
dc.contributor.authorProkopenko I
dc.contributor.authorPsaty BM
dc.contributor.authorReincke M
dc.contributor.authorRimm EB
dc.contributor.authorRotter JI
dc.contributor.authorSaint-Pierre A
dc.contributor.authorSchurmann C
dc.contributor.authorSeshadri S
dc.contributor.authorSjögren K
dc.contributor.authorSlagboom P
dc.contributor.authorStrickler HD
dc.contributor.authorStumvoll M
dc.contributor.authorSuh Y
dc.contributor.authorSun Q
dc.contributor.authorZhang C
dc.contributor.authorSvensson J
dc.contributor.authorTanaka T
dc.contributor.authorTare A
dc.contributor.authorTönjes A
dc.contributor.authorUh HW
dc.contributor.authorvan Duijn CM
dc.contributor.authorvan Heemst D
dc.contributor.authorVandenput L
dc.contributor.authorVasan RS
dc.contributor.authorVölker U
dc.contributor.authorWillems SM
dc.contributor.authorOhlsson C
dc.contributor.authorWallaschofski H
dc.contributor.authorKaplan RC
dc.date.accessioned2018-10-01T09:41:46Z
dc.date.available2018-10-01T09:41:46Z
dc.date.issued2017
dc.identifier.issn1474-9718
dc.identifier.urihttp://dx.doi.org/10.1111/acel.12612
dc.identifier.urihttp://hdl.handle.net/10863/6221
dc.description.abstractThe 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_US
dc.language.isoenen_US
dc.rights
dc.titleGenomewide meta-analysis identifies loci associated with IGF-I and IGEBP-3 levels with impact on age-related traits (vol 15, pg 811, 2016) [erratum]en_US
dc.typeArticleen_US
dc.date.updated2018-10-01T09:36:38Z
dc.language.isiEN-GB
dc.journal.titleAging Cell
dc.description.fulltextopenen_US


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