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 Jager & 117 others Abraham 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 C 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

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

Fingerprint

gene expression
Gene expression
genes
blood
methylation
Blood
Methylation
Genes
Aging of materials
fasting
bionics
Gene Expression
blood pressure
Biological Models
harbors
Disease Susceptibility
cholesterol
Blood pressure
Ports and harbors
predictions

ASJC Scopus subject areas

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

Cite this

Peters, M. J., Joehanes, R., Pilling, L. C., Schurmann, C., Conneely, K. N., Powell, J., ... Singleton, A. B. (2015). The transcriptional landscape of age in human peripheral blood. Nature Communications, 6, [8570]. https://doi.org/10.1038/ncomms9570

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 C; 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 journalArticle

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, 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, HJ, 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, HJ, 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, YDI, 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, Nalls, MA, Hernandez, DG, Cookson, MR, Gibbs, RJ, Hardy, J, Ramasamy, A, Zonderman, AB, Dillman, A, Traynor, B, Smith, C, Longo, DL, Trabzuni, D, Troncoso, JC, Van Der Brug, M, Weale, ME, O'Brien, R, Johnson, R, Walker, R, Zielke, RH, Arepalli, S, Ryten, M & Singleton, AB 2015, 'The transcriptional landscape of age in human peripheral blood', Nature Communications, vol. 6, 8570. https://doi.org/10.1038/ncomms9570
Peters MJ, Joehanes R, Pilling LC, Schurmann C, Conneely KN, Powell J et al. The transcriptional landscape of age in human peripheral blood. Nature Communications. 2015 Oct 22;6. 8570. https://doi.org/10.1038/ncomms9570
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 C ; Van Der Brug, Marcel ; Weale, Michael E. ; O'Brien, Richard ; Johnson, Robert ; Walker, Robert ; Zielke, Ronald H. ; Arepalli, Sampath ; Ryten, Mina ; Singleton, Andrew B. / The transcriptional landscape of age in human peripheral blood. In: Nature Communications. 2015 ; Vol. 6.
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title = "The transcriptional landscape of age in human peripheral blood",
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.",
author = "Peters, {Marjolein J.} and Roby Joehanes and Pilling, {Luke C.} and Claudia Schurmann and Conneely, {Karen N.} and Joseph Powell and Eva Reinmaa and Sutphin, {George L.} and Alexandra Zhernakova and Katharina Schramm and Wilson, {Yana A.} and Sayuko Kobes and Taru Tukiainen and Ramos, {Yolande F.} and G{\"o}ring, {Harald H H} and Myriam Fornage and Yongmei Liu and Gharib, {Sina A.} and Stranger, {Barbara E.} and {De Jager}, {Philip L.} and Abraham Aviv and Daniel Levy and Murabito, {Joanne M.} and Munson, {Peter J.} and Tianxiao Huan and Albert Hofman and Uitterlinden, {Andr{\'e} G.} and Fernando Rivadeneira and {Van Rooij}, Jeroen and Lisette Stolk and Linda Broer and Verbiest, {Michael M P J} and Mila Jhamai and Pascal Arp and Andres Metspalu and Liina Tserel and Lili Milani and Samani, {Nilesh J.} and P{\"a}rt Peterson and Silva Kasela and Veryan Codd and Annette Peters and Ward-Caviness, {Cavin K.} and Christian Herder and Melanie Waldenberger and Michael Roden and Paula Singmann and Sonja Zeilinger and Thomas Illig and Georg Homuth and Grabe, {Hans J{\"o}rgen} and Henry V{\"o}lzke and Leif Steil and Thomas Kocher and Anna Murray and David Melzer and Hanieh Yaghootkar and Stefania Bandinelli and Moses, {Eric K.} and Kent, {Jack W.} and Curran, {Joanne E.} and Johnson, {Matthew P.} and Sarah Williams-Blangero and Westra, {Harm Jan} and McRae, {Allan F.} and Smith, {Jennifer A.} and Kardia, {Sharon L R} and Iiris Hovatta and Markus Perola and Samuli Ripatti and Veikko Salomaa and Henders, {Anjali K.} and Martin, {Nicholas G.} and Smith, {Alicia K.} and Divya Mehta and Binder, {Elisabeth B.} and Nylocks, {K. Maria} and Kennedy, {Elizabeth M.} and Torsten Klengel and Jingzhong Ding and Suchy-Dicey, {Astrid M.} and Enquobahrie, {Daniel A.} and Jennifer Brody and Rotter, {Jerome I.} and Chen, {Yii Der I} and Jeanine Houwing-Duistermaat and Margreet Kloppenburg and Slagboom, {P. Eline} and Quinta Helmer and {Den Hollander}, Wouter and Shannon Bean and Towfique Raj and Noman Bakhshi and Wang, {Qiao Ping} and Oyston, {Lisa J.} and Psaty, {Bruce M.} and Tracy, {Russell P.} and Montgomery, {Grant W.} and Turner, {Stephen T.} and John Blangero and Ingrid Meulenbelt and Ressler, {Kerry J.} and Jian Yang and Lude Franke and Johannes Kettunen and Visscher, {Peter M.} and Neely, {G. Gregory} and Ron Korstanje and Hanson, {Robert L.} and Holger Prokisch and Luigi Ferrucci and Tonu Esko and Alexander Teumer and {Van Meurs}, {Joyce B J} and Johnson, {Andrew D.} and Nalls, {Michael A.} and Hernandez, {Dena G.} and Cookson, {Mark R.} and Gibbs, {Raphael J.} and John Hardy and Adaikalavan Ramasamy and Zonderman, {Alan B.} and Allissa Dillman and Bryan Traynor and Colin Smith and Longo, {Dan L.} and Daniah Trabzuni and Troncoso, {Juan C} and {Van Der Brug}, Marcel and Weale, {Michael E.} and Richard O'Brien and Robert Johnson and Robert Walker and Zielke, {Ronald H.} and Sampath Arepalli and Mina Ryten and Singleton, {Andrew B.}",
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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 C

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.

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.

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U2 - 10.1038/ncomms9570

DO - 10.1038/ncomms9570

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JO - Nature Communications

JF - Nature Communications

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