Teumer, Alexander and Qi, Qibin and Nethander, Maria and Aschard, Hugues and Bandinelli, Stefania and Beekman, Marian and Berndt, Sonja I. and Bidlingmaier, Martin and Broer, Linda and Cappola, Anne and Ceda, Gian Paolo and Chanock, Stephen and Chen, Ming-Huei and Chen, Tai C. and Chen, Yii-Der Ida and Chung, Jonathan and Miglianico, Fabiola Del Greco and Eriksson, Joel and Ferrucci, Luigi and Friedrich, Nele and Gnewuch, Carsten and Goodarzi, Mark O. and Grarup, Niels and Guo, Tingwei and Hammer, Elke and Hayes, Richard B. and Hicks, Andrew A. and Hofman, Albert and Houwing-Duistermaat, Jeanine J. and Hu, Frank and Hunter, David J. and Husemoen, Lise L. and Isaacs, Aaron and Jacobs, Kevin B. and Janssen, Joop A. M. J. L. and Jansson, John-Olov and Jehmlich, Nico and Johnson, Simon and Juul, Anders and Karlsson, Magnus and Kilpelainen, Tuomas O. and Kovacs, Peter and Kraft, Peter and Li, Chao and Linneberg, Allan and Liu, Yongmei and Loos, Ruth J. F. and Lorentzon, Mattias and Lu, Yingchang and Maggio, Marcello and Magi, Reedik and Meigs, James and Mellstrom, Dan and Nauck, Matthias and Newman, Anne B. and Pollak, Michael N. and Pramstaller, Peter P. and Prokopenko, Inga and Psaty, Bruce M. and Reincke, Martin and Rimm, Eric B. and Rotter, Jerome I. and Saint Pierre, Aude and Schurmann, Claudia and Seshadri, Sudha and Sjogren, Klara and Slagboom, P. Eline and Strickler, Howard D. and Stumvoll, Michael and Suh, Yousin and Sun, Qi and Zhang, Cuilin and Svensson, Johan and Tanaka, Toshiko and Tare, Archana and Toenjes, Anke and Uh, Hae-Won and van Duijn, Cornelia M. and van Heemst, Diana and Vandenput, Liesbeth and Vasan, Ramachandran S. and Voelker, Uwe and Willems, Sara M. and Ohlsson, Claes and Wallaschofski, Henri and Kaplan, Robert C. (2016) Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits. AGING CELL, 15 (5). pp. 811-824. ISSN 1474-9718, 1474-9726
Full text not available from this repository. (Request a copy)Abstract
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 30884 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 90years. 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; CIRCULATING LEVELS; GENETIC-VARIATION; FACTOR (IGF)-I; CANCER-RISK; INSULIN; DISEASE; aging; genomewide association study; growth hormone axis; IGF-I; IGFBP-3; longevity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Apr 2019 11:30 |
| Last Modified: | 05 Apr 2019 11:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4161 |
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