Blood RNA expression profiles undergo major changes during the seventh decade
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Marius Gheorghe1, Claudia Schurmann3,6 Marjolein J. Peters2, André G. Uitterlinden2,5, Albert Hofman2,5, Reiner Biffar7, Georg Homuth3, Uwe Völker3, Joyce BJ van Meurs2, Vered Raz4
1Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
2Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
3Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, 17475 DE, Germany
4Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, 2300 RC, The Netherlands
5Department of Epidemiology, Erasmus University Medical Center, Rotterdam, 3000 CA, The Netherlands
6The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America
7Department of Prosthodontics, Gerodontology and Biomaterials, University Medicine Greifswald, Greifswald, 17475 DE, Germany
Vered Raz, email: [email protected]
Keywords: blood aging, population based studies, RNA expression profiles, sample weighting, b-spline regression model
Received: June 06, 2016 Accepted: September 05, 2016 Published: September 17, 2016
Genome-wide alterations in RNA expression profiles are age-associated. Yet the rate and temporal pattern of those alterations are poorly understood. We investigated temporal changes in RNA expression profiles in blood from population-based studies using a quadratic regression model. Comparative analysis between two independent studies was carried out after sample-weighting that downsized differences in sample distribution over age between the datasets. We show that age-associated expression profiles are clustered into two major inclinations and transcriptional alternations occur predominantly from the seventh decade onwards. The age-associated genes in blood are enriched in functional groups of the translational machinery and the immune system. The results are highly consistent between the two population-based studies indicating that our analysis overcomes potential confounders in population-based studies. We suggest that the critical age when major transcriptional alterations occur could help understanding aging and disease risk during adulthood.
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