Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes (Articolo in rivista)

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  • Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Alternative label
  • Garagnani, P. and Giuliani, C. and Pirazzini, C. and Olivieri, F. and Bacalini, M. G. and Ostan, R. and Mari, D. and Passarino, G. and Monti, D. and Bonfigli, A. R. and Boemi, M. and Ceriello, A. and Genovese, S. and Sevini, F. and Luiselli, D. and Tieri, P. and Capri, M. and Salvioli, S. and Vijg, J. and Suh, Y. and Delledonne, M. and Testa, R. and Franceschi, C. (2013)
    Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes
    in Aging (Albany, N.Y. Online)
    (literal)
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  • Garagnani, P. and Giuliani, C. and Pirazzini, C. and Olivieri, F. and Bacalini, M. G. and Ostan, R. and Mari, D. and Passarino, G. and Monti, D. and Bonfigli, A. R. and Boemi, M. and Ceriello, A. and Genovese, S. and Sevini, F. and Luiselli, D. and Tieri, P. and Capri, M. and Salvioli, S. and Vijg, J. and Suh, Y. and Delledonne, M. and Testa, R. and Franceschi, C. (literal)
Pagina inizio
  • 373 (literal)
Pagina fine
  • 85 (literal)
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  • 1945-4589 Garagnani, Paolo Giuliani, Cristina Pirazzini, Chiara Olivieri, Fabiola Bacalini, Maria Giulia Ostan, Rita Mari, Daniela Passarino, Giuseppe Monti, Daniela Bonfigli, Anna Rita Boemi, Massimo Ceriello, Antonio Genovese, Stefano Sevini, Federica Luiselli, Donata Tieri, Paolo Capri, Miriam Salvioli, Stefano Vijg, Jan Suh, Yousin Delledonne, Massimo Testa, Roberto Franceschi, Claudio Journal Article Research Support, Non-U.S. Gov't United States Aging (Albany NY). 2013 May;5(5):373-85. (literal)
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  • 5 (literal)
Rivista
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  • 5 (literal)
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  • 1 DIMES - Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, 40126 Italy 2 C.I.G. Interdepartmental Center \"L. Galvani\", University of Bologna, Bologna, Italy 3 CRBA - Applied Biomedical Research Center, S. Orsola-Malpighi Polyclinic, Bologna, 40138 Italy 4 Department of Biological, Geological and Environmental Sciences, Laboratory of Molecular Anthropology & Centre for Genome Biology, University of Bologna, Bologna 40126, Italy 5 Department of Clinical and Molecular Sciences, Universita? Politecnica delle Marche, Ancona, Italy 6 Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging INRCA-IRCCS, Ancona, Italy 7 Geriatric Unit IRCCS Ca' Granda Foundation Maggiore Policlinico Hospital and Department of Clinical Sciences and Community Health, University of Milano, Italy 8 Department of Cell Biology, University of Calabria, Rende, Italy 9 Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy 10 Metabolic Diseases and Diabetology Unit, IRCCS-INRCA, Ancona, Italy 11 Institut d'Investigacions Biome?diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain 12 Centro de Investigacio?n Biome?dica en Red de Diabetes y Enfermedades Metabo?licas Asociadas (CIBERDEM), Barcelona, Spain 13 Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica Sesto San Giovanni (MI), Italy 14 IAC-CNR Istituto per le Applicazioni del Calcolo, Consiglio Nazionale delle Ricerche, Rome, Italy 15 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA 16 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA 17 Institute for Aging Research, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA 18 Institute of Aging Research, Guangdong Medical College, Dongguan 523808, China 19 Personal Genomics SRL, Strada le Grazie 15, 37133 Verona - Italy 20 Functional Genomics Center, Dept. of Biotechnologies, University of Verona, Strada le Grazie 15, 37133 Verona - Italy 21 Experimental Models in Clinical Pathology, IRCCS-INRCA, Ancona, Italy (literal)
Titolo
  • Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: a proof of principle on type 2 diabetes (literal)
Abstract
  • Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10(-)(7)). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared. (literal)
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