Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits
| Autor: | Teumer, Alexander, Qi, Qibin, Nethander, Maria, Aschard, Hugues, Bandinelli, Stefania, Beekman, Marian, Berndt, Sonja, Bidlingmaier, Martin, Broer, Linda, Cappola, Anne, Ceda, Gian Paolo, Chanock, Stephen, Chen, Ming-Huei, Chen, Tai, Chen, Yii-Der Ida, Chung, Jonathan, Del Greco Miglianico, Fabiola, Eriksson, Joel, Ferrucci, Luigi, Friedrich, Nele, Gnewuch, Carsten, Goodarzi, Mark, Grarup, Niels, Guo, Tingwei, Hammer, Elke, Hayes, Richard, Hicks, Andrew, Hofman, Albert, Houwing-Duistermaat, Jeanine, Hu, Frank, Hunter, David, Husemoen, Lise, Isaacs, Aaron, Jacobs, Kevin, Janssen, Joop, Jansson, John-Olov, Jehmlich, Nico, Johnson, Simon, Juul, Anders, Karlsson, Magnus, Kilpelainen, Tuomas, Kovacs, Peter, Kraft, Peter, Li, Chao, Linneberg, Allan, Liu, Yongmei, Loos, Ruth, Lorentzon, Mattias, Lu, Yingchang, Maggio, Marcello, Magi, Reedik, Meigs, James, Mellström, Dan, Nauck, Matthias, Newman, Anne, Pollak, Michael, Pramstaller, Peter, Prokopenko, Inga, Psaty, Bruce, Reincke, Martin, Rimm, Eric, Rotter, Jerome, Saint Pierre, Aude, Schurmann, Claudia, Seshadri, Sudha, Sjögren, Klara, Slagboom, P Eline, Strickler, Howard, Stumvoll, Michael, Suh, Yousin, Sun, Qi, Zhang, Cuilin, Svensson, Johan, Tanaka, Toshiko, Tare, Archana, Tönjes, Anke, Uh, Hae-Won, Van Duijn, Cornelia, van Heemst, Diana, Vandenput, Liesbeth, Vasan, Ramachandran, Völker, Uwe, Willems, Sara, Ohlsson, Claes, Wallaschofski, Henri, Kaplan, Robert, Chen, Ming‐Huei, Chen, Yii‐Der Ida, Houwing‐Duistermaat, Jeanine, Jansson, John‐Olov, Slagboom, P. Eline, Uh, Hae‐Won, Heemst, Diana |
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| Přispěvatelé: | King‘s College London, Harvard School of Public Health, Azienda Sanitaria Firenze, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Munich, Germany, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, RS: FHML MaCSBio, Biochemie, Internal Medicine, Epidemiology |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Aging MESH: Insulin-Like Growth Factor I IGFBP3 Genome-wide association study Regulatory Sequences Nucleic Acid Cardiovascular Medical and Health Sciences MESH: Quantitative Trait Heritable 2.1 Biological and endogenous factors MESH: Aging Insulin-Like Growth Factor I Aetiology Genetics [STAT.AP]Statistics [stat]/Applications [stat.AP] MESH: Insulin-Like Growth Factor Binding Protein 3 11 Medical And Health Sciences Biological Sciences growth hormone axis MESH: Gene Expression Regulation IGF-I Metabolome Female Erratum [STAT.ME]Statistics [stat]/Methodology [stat.ME] MESH: Metabolome CHARGE Longevity Working Group Adult Quantitative Trait Loci Single-nucleotide polymorphism Locus (genetics) Body Composition Genetics Consortium Quantitative trait locus Biology 03 medical and health sciences Quantitative Trait Quantitative Trait Heritable longevity Clinical Research SNP MESH: Regulatory Sequences Nucleic Acid Humans Allele Heritable Metabolic and endocrine genomewide association study MESH: Humans Nucleic Acid aging MESH: Adult IGFBP-3 Cell Biology 06 Biological Sciences MESH: Quantitative Trait Loci MESH: Male 030104 developmental biology Insulin-Like Growth Factor Binding Protein 3 [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Gene Expression Regulation Expression quantitative trait loci MESH: Genome-Wide Association Study [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] MESH: Female Regulatory Sequences Genome-Wide Association Study Developmental Biology |
| Zdroj: | Aging Cell Aging Cell, 15(5), 811-824 Aging cell, vol 15, iss 5 Aging Cell, Wiley Open Access, 2016, 15 (5), pp.811-824. ⟨10.1111/acel.12490⟩ Aging Cell, 15(5), 811-824. Wiley-Blackwell Aging Cell, 15(5), 811-824. Wiley-Blackwell Publishing Ltd |
| ISSN: | 1474-9718 1474-9726 |
| DOI: | 10.1111/acel.12490 |
| Popis: | 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. ? 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. |
| Databáze: | OpenAIRE |
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