Genomewide meta‐analysis identifies loci associated with IGF‐I and IGFBP‐3 levels with impact on age‐related traits

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Author
Teumer, Alexander
Qi, Qibin
Nethander, Maria
Bandinelli, Stefania
Beekman, Marian
Berndt, Sonja I.
Bidlingmaier, Martin
Broer, Linda
Cappola, Anne
Ceda, Gian Paolo
Chanock, Stephen
Chen, Ming‐Huei
Chen, Tai C.
Chen, Yii‐Der Ida
Chung, Jonathan
Del Greco Miglianico, Fabiola
Eriksson, Joel
Ferrucci, Luigi
Friedrich, Nele
Gnewuch, Carsten
Goodarzi, Mark O.
Grarup, Niels
Guo, Tingwei
Hammer, Elke
Hayes, Richard B.
Hicks, Andrew A.
Hofman, Albert
Houwing‐Duistermaat, Jeanine J.
Husemoen, Lise L.
Isaacs, Aaron
Jacobs, Kevin B.
Janssen, Joop A. M. J. L.
Jansson, John‐Olov
Jehmlich, Nico
Johnson, Simon
Juul, Anders
Karlsson, Magnus
Kilpelainen, Tuomas O.
Kovacs, Peter
Li, Chao
Linneberg, Allan
Liu, Yongmei
Loos, Ruth J. F.
Lorentzon, Mattias
Lu, Yingchang
Maggio, Marcello
Magi, Reedik
Mellström, Dan
Nauck, Matthias
Newman, Anne B.
Pollak, Michael N.
Pramstaller, Peter P.
Prokopenko, Inga
Psaty, Bruce M.
Reincke, Martin
Rotter, Jerome I.
Saint Pierre, Aude
Schurmann, Claudia
Seshadri, Sudha
Sjögren, Klara
Slagboom, P. Eline
Strickler, Howard D.
Stumvoll, Michael
Suh, Yousin
Zhang, Cuilin
Svensson, Johan
Tanaka, Toshiko
Tare, Archana
Tönjes, Anke
Uh, Hae‐Won
van Duijn, Cornelia M.
van Heemst, Diana
Vandenput, Liesbeth
Vasan, Ramachandran S.
Völker, Uwe
Willems, Sara M.
Ohlsson, Claes
Wallaschofski, Henri
Kaplan, Robert C.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1111/acel.12490Metadata
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Teumer, 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.Abstract
Summary 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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013013/pdf/Terms of Use
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