The transcriptional landscape of age in human peripheral blood.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Peters, MJ; Joehanes, R; Pilling, LC; Schurmann, C; Conneely, KN; Powell, J; Reinmaa, E; Sutphin, GL; Zhernakova, A; Schramm, K; Wilson, YA; Kobes, S; Tukiainen, T; NABEC/UKBEC Consortium, ; Ramos, YF; Göring, HHH; Fornage, M; Liu, Y; Gharib, SA; Stranger, BE; De Jager, PL; Aviv, A; Levy, D; Murabito, JM; Munson, PJ; Huan, T; Hofman, A; Uitterlinden, AG; Rivadeneira, F; van Rooij, J; Stolk, L; Broer, L; Verbiest, MMPJ; Jhamai, M; Arp, P; Metspalu, A; Tserel, L; Milani, L; Samani, NJ; Peterson, P; Kasela, S; Codd, V; Peters, A; Ward-Caviness, CK; Herder, C; Waldenberger, M; Roden, M; Singmann, P; Zeilinger, S; Illig, T; Homuth, G; Grabe, H-J; Völzke, H; Steil, L; Kocher, T; Murray, A; Melzer, D; Yaghootkar, H; Bandinelli, S; Moses, EK; Kent, JW; Curran, JE; Johnson, MP; Williams-Blangero, S; Westra, H-J; McRae, AF; Smith, JA; Kardia, SLR; Hovatta, I; Perola, M; Ripatti, S; Salomaa, V; Henders, AK; Martin, NG; Smith, AK; Mehta, D; Binder, EB; Nylocks, KM; Kennedy, EM; Klengel, T; Ding, J; Suchy-Dicey, AM; Enquobahrie, DA; Brody, J; Rotter, JI; Chen, Y-DI; Houwing-Duistermaat, J; Kloppenburg, M; Slagboom, PE; Helmer, Q; den Hollander, W; Bean, S; Raj, T; Bakhshi, N; Wang, QP; Oyston, LJ; Psaty, BM; Tracy, RP; Montgomery, GW; Turner, ST; Blangero, J; Meulenbelt, I; Ressler, KJ; Yang, J; Franke, L; Kettunen, J; Visscher, PM; Neely, GG; Korstanje, R; Hanson, RL; Prokisch, H; Ferrucci, L; Esko, T; Teumer, A; van Meurs, JBJ; Johnson, AD

Published Date

  • October 22, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 8570 -

PubMed ID

  • 26490707

Pubmed Central ID

  • 26490707

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms9570

Language

  • eng

Conference Location

  • England