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 language | English (US) |
|---|---|
| Article number | 8570 |
| Journal | Nature communications |
| Volume | 6 |
| DOIs | |
| State | Published - Oct 22 2015 |
| Externally published | Yes |
ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
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The transcriptional landscape of age in human peripheral blood. / Peters, Marjolein J.; Joehanes, Roby; Pilling, Luke C.; Schurmann, Claudia; Conneely, Karen N.; Powell, Joseph; Reinmaa, Eva; Sutphin, George L.; Zhernakova, Alexandra; Schramm, Katharina; Wilson, Yana A.; Kobes, Sayuko; Tukiainen, Taru; Ramos, Yolande F.; Göring, Harald H.H.; Fornage, Myriam; Liu, Yongmei; Gharib, Sina A.; Stranger, Barbara E.; De Jager, Philip L.; Aviv, Abraham; Levy, Daniel; Murabito, Joanne M.; Munson, Peter J.; Huan, Tianxiao; Hofman, Albert; Uitterlinden, André G.; Rivadeneira, Fernando; Van Rooij, Jeroen; Stolk, Lisette; Broer, Linda; Verbiest, Michael M.P.J.; Jhamai, Mila; Arp, Pascal; Metspalu, Andres; Tserel, Liina; Milani, Lili; Samani, Nilesh J.; Peterson, Pärt; Kasela, Silva; Codd, Veryan; Peters, Annette; Ward-Caviness, Cavin K.; Herder, Christian; Waldenberger, Melanie; Roden, Michael; Singmann, Paula; Zeilinger, Sonja; Illig, Thomas; Homuth, Georg; Grabe, Hans Jörgen; Völzke, Henry; Steil, Leif; Kocher, Thomas; Murray, Anna; Melzer, David; Yaghootkar, Hanieh; Bandinelli, Stefania; Moses, Eric K.; Kent, Jack W.; Curran, Joanne E.; Johnson, Matthew P.; Williams-Blangero, Sarah; Westra, Harm Jan; McRae, Allan F.; Smith, Jennifer A.; Kardia, Sharon L.R.; Hovatta, Iiris; Perola, Markus; Ripatti, Samuli; Salomaa, Veikko; Henders, Anjali K.; Martin, Nicholas G.; Smith, Alicia K.; Mehta, Divya; Binder, Elisabeth B.; Nylocks, K. Maria; Kennedy, Elizabeth M.; Klengel, Torsten; Ding, Jingzhong; Suchy-Dicey, Astrid M.; Enquobahrie, Daniel A.; Brody, Jennifer; Rotter, Jerome I.; Chen, Yii Der I.; Houwing-Duistermaat, Jeanine; Kloppenburg, Margreet; Slagboom, P. Eline; Helmer, Quinta; Den Hollander, Wouter; Bean, Shannon; Raj, Towfique; Bakhshi, Noman; Wang, Qiao Ping; Oyston, Lisa J.; Psaty, Bruce M.; Tracy, Russell P.; Montgomery, Grant W.; Turner, Stephen T.; Blangero, John; Meulenbelt, Ingrid; Ressler, Kerry J.; Yang, Jian; Franke, Lude; Kettunen, Johannes; Visscher, Peter M.; Neely, G. Gregory; Korstanje, Ron; Hanson, Robert L.; Prokisch, Holger; Ferrucci, Luigi; Esko, Tonu; Teumer, Alexander; Van Meurs, Joyce B.J.; Johnson, Andrew D.; Nalls, Michael A.; Hernandez, Dena G.; Cookson, Mark R.; Gibbs, Raphael J.; Hardy, John; Ramasamy, Adaikalavan; Zonderman, Alan B.; Dillman, Allissa; Traynor, Bryan; Smith, Colin; Longo, Dan L.; Trabzuni, Daniah; Troncoso, Juan; Van Der Brug, Marcel; Weale, Michael E.; O'Brien, Richard; Johnson, Robert; Walker, Robert; Zielke, Ronald H.; Arepalli, Sampath; Ryten, Mina; Singleton, Andrew B.
In: Nature communications, Vol. 6, 8570, 22.10.2015.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The transcriptional landscape of age in human peripheral blood
AU - Peters, Marjolein J.
AU - Joehanes, Roby
AU - Pilling, Luke C.
AU - Schurmann, Claudia
AU - Conneely, Karen N.
AU - Powell, Joseph
AU - Reinmaa, Eva
AU - Sutphin, George L.
AU - Zhernakova, Alexandra
AU - Schramm, Katharina
AU - Wilson, Yana A.
AU - Kobes, Sayuko
AU - Tukiainen, Taru
AU - Ramos, Yolande F.
AU - Göring, Harald H.H.
AU - Fornage, Myriam
AU - Liu, Yongmei
AU - Gharib, Sina A.
AU - Stranger, Barbara E.
AU - De Jager, Philip L.
AU - Aviv, Abraham
AU - Levy, Daniel
AU - Murabito, Joanne M.
AU - Munson, Peter J.
AU - Huan, Tianxiao
AU - Hofman, Albert
AU - Uitterlinden, André G.
AU - Rivadeneira, Fernando
AU - Van Rooij, Jeroen
AU - Stolk, Lisette
AU - Broer, Linda
AU - Verbiest, Michael M.P.J.
AU - Jhamai, Mila
AU - Arp, Pascal
AU - Metspalu, Andres
AU - Tserel, Liina
AU - Milani, Lili
AU - Samani, Nilesh J.
AU - Peterson, Pärt
AU - Kasela, Silva
AU - Codd, Veryan
AU - Peters, Annette
AU - Ward-Caviness, Cavin K.
AU - Herder, Christian
AU - Waldenberger, Melanie
AU - Roden, Michael
AU - Singmann, Paula
AU - Zeilinger, Sonja
AU - Illig, Thomas
AU - Homuth, Georg
AU - Grabe, Hans Jörgen
AU - Völzke, Henry
AU - Steil, Leif
AU - Kocher, Thomas
AU - Murray, Anna
AU - Melzer, David
AU - Yaghootkar, Hanieh
AU - Bandinelli, Stefania
AU - Moses, Eric K.
AU - Kent, Jack W.
AU - Curran, Joanne E.
AU - Johnson, Matthew P.
AU - Williams-Blangero, Sarah
AU - Westra, Harm Jan
AU - McRae, Allan F.
AU - Smith, Jennifer A.
AU - Kardia, Sharon L.R.
AU - Hovatta, Iiris
AU - Perola, Markus
AU - Ripatti, Samuli
AU - Salomaa, Veikko
AU - Henders, Anjali K.
AU - Martin, Nicholas G.
AU - Smith, Alicia K.
AU - Mehta, Divya
AU - Binder, Elisabeth B.
AU - Nylocks, K. Maria
AU - Kennedy, Elizabeth M.
AU - Klengel, Torsten
AU - Ding, Jingzhong
AU - Suchy-Dicey, Astrid M.
AU - Enquobahrie, Daniel A.
AU - Brody, Jennifer
AU - Rotter, Jerome I.
AU - Chen, Yii Der I.
AU - Houwing-Duistermaat, Jeanine
AU - Kloppenburg, Margreet
AU - Slagboom, P. Eline
AU - Helmer, Quinta
AU - Den Hollander, Wouter
AU - Bean, Shannon
AU - Raj, Towfique
AU - Bakhshi, Noman
AU - Wang, Qiao Ping
AU - Oyston, Lisa J.
AU - Psaty, Bruce M.
AU - Tracy, Russell P.
AU - Montgomery, Grant W.
AU - Turner, Stephen T.
AU - Blangero, John
AU - Meulenbelt, Ingrid
AU - Ressler, Kerry J.
AU - Yang, Jian
AU - Franke, Lude
AU - Kettunen, Johannes
AU - Visscher, Peter M.
AU - Neely, G. Gregory
AU - Korstanje, Ron
AU - Hanson, Robert L.
AU - Prokisch, Holger
AU - Ferrucci, Luigi
AU - Esko, Tonu
AU - Teumer, Alexander
AU - Van Meurs, Joyce B.J.
AU - Johnson, Andrew D.
AU - Nalls, Michael A.
AU - Hernandez, Dena G.
AU - Cookson, Mark R.
AU - Gibbs, Raphael J.
AU - Hardy, John
AU - Ramasamy, Adaikalavan
AU - Zonderman, Alan B.
AU - Dillman, Allissa
AU - Traynor, Bryan
AU - Smith, Colin
AU - Longo, Dan L.
AU - Trabzuni, Daniah
AU - Troncoso, Juan
AU - Van Der Brug, Marcel
AU - Weale, Michael E.
AU - O'Brien, Richard
AU - Johnson, Robert
AU - Walker, Robert
AU - Zielke, Ronald H.
AU - Arepalli, Sampath
AU - Ryten, Mina
AU - Singleton, Andrew B.
N1 - Funding Information: The infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant R01HL105756. This study was funded by the European Commission (HEALTH-F2-2008-201865, GEFOS; HEALTH-F2-2008 35627, TREAT-OA), the Netherlands Organization for Scientific Research (NWO) Investments (nr. 175.010.2005.011, 911-03-012), the Netherlands Consortium for Healthy Aging , the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810 and VIDI grant 917103521. Additional acknowledgments to specific cohorts and their support are found in Supplementary Notes 1 and 2.
PY - 2015/10/22
Y1 - 2015/10/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84945143930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945143930&partnerID=8YFLogxK
U2 - 10.1038/ncomms9570
DO - 10.1038/ncomms9570
M3 - Article
C2 - 26490707
AN - SCOPUS:84945143930
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 8570
ER -