The transcriptional landscape of age in human peripheral blood

Marjolein J. Peters, Roby Joehanes, Luke C. Pilling, Claudia Schurmann, Karen N. Conneely, Joseph Powell, Eva Reinmaa, George L. Sutphin, Alexandra Zhernakova, Katharina Schramm, Yana A. Wilson, Sayuko Kobes, Taru Tukiainen, Yolande F. Ramos, Harald H.H. Göring, Myriam Fornage, Yongmei Liu, Sina A. Gharib, Barbara E. Stranger, Philip L. De JagerAbraham Aviv, Daniel Levy, Joanne M. Murabito, Peter J. Munson, Tianxiao Huan, Albert Hofman, André G. Uitterlinden, Fernando Rivadeneira, Jeroen Van Rooij, Lisette Stolk, Linda Broer, Michael M.P.J. Verbiest, Mila Jhamai, Pascal Arp, Andres Metspalu, Liina Tserel, Lili Milani, Nilesh J. Samani, Pärt Peterson, Silva Kasela, Veryan Codd, Annette Peters, Cavin K. Ward-Caviness, Christian Herder, Melanie Waldenberger, Michael Roden, Paula Singmann, Sonja Zeilinger, Thomas Illig, Georg Homuth, Hans Jörgen Grabe, Henry Völzke, Leif Steil, Thomas Kocher, Anna Murray, David Melzer, Hanieh Yaghootkar, Stefania Bandinelli, Eric K. Moses, Jack W. Kent, Joanne E. Curran, Matthew P. Johnson, Sarah Williams-Blangero, Harm Jan Westra, Allan F. McRae, Jennifer A. Smith, Sharon L.R. Kardia, Iiris Hovatta, Markus Perola, Samuli Ripatti, Veikko Salomaa, Anjali K. Henders, Nicholas G. Martin, Alicia K. Smith, Divya Mehta, Elisabeth B. Binder, K. Maria Nylocks, Elizabeth M. Kennedy, Torsten Klengel, Jingzhong Ding, Astrid M. Suchy-Dicey, Daniel A. Enquobahrie, Jennifer Brody, Jerome I. Rotter, Yii Der I. Chen, Jeanine Houwing-Duistermaat, Margreet Kloppenburg, P. Eline Slagboom, Quinta Helmer, Wouter Den Hollander, Shannon Bean, Towfique Raj, Noman Bakhshi, Qiao Ping Wang, Lisa J. Oyston, Bruce M. Psaty, Russell P. Tracy, Grant W. Montgomery, Stephen T. Turner, John Blangero, Ingrid Meulenbelt, Kerry J. Ressler, Jian Yang, Lude Franke, Johannes Kettunen, Peter M. Visscher, G. Gregory Neely, Ron Korstanje, Robert L. Hanson, Holger Prokisch, Luigi Ferrucci, Tonu Esko, Alexander Teumer, Joyce B.J. Van Meurs, Andrew D. Johnson, Michael A. Nalls, Dena G. Hernandez, Mark R. Cookson, Raphael J. Gibbs, John Hardy, Adaikalavan Ramasamy, Alan B. Zonderman, Allissa Dillman, Bryan Traynor, Colin Smith, Dan L. Longo, Daniah Trabzuni, Juan Troncoso, Marcel Van Der Brug, Michael E. Weale, Richard O'Brien, Robert Johnson, Robert Walker, Ronald H. Zielke, Sampath Arepalli, Mina Ryten, Andrew B. Singleton

Research output: Contribution to journalArticle

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Abstract

Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.

Original languageEnglish (US)
Article number8570
JournalNature communications
Volume6
DOIs
StatePublished - Oct 22 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Peters, M. J., Joehanes, R., Pilling, L. C., Schurmann, C., Conneely, K. N., Powell, J., Reinmaa, E., Sutphin, G. L., Zhernakova, A., Schramm, K., Wilson, Y. A., Kobes, S., Tukiainen, T., Ramos, Y. F., Göring, H. H. H., Fornage, M., Liu, Y., Gharib, S. A., Stranger, B. E., ... Singleton, A. B. (2015). The transcriptional landscape of age in human peripheral blood. Nature communications, 6, [8570]. https://doi.org/10.1038/ncomms9570