The transcriptional landscape of age in human peripheral blood

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

doi:10.1038/ncomms9570

The transcriptional landscape of age in human peripheral blood

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

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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 language	Undefined/Unknown
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9570
Publication status	Published - 2015

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Peters, M., 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., Goring, HHH., Fornage, M., Liu, YM., Gharib, SA., Stranger, BE., ... Andrew, D. (2015). The transcriptional landscape of age in human peripheral blood. Nature Communications, 6. https://doi.org/10.1038/ncomms9570

Peters, Marjolein ; 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 ; Goring, HHH ; Fornage, M ; Liu, YM ; Gharib, SA ; Stranger, BE ; De Jager, PL ; Aviv, A ; Levy, D ; Murabito, JM ; Munson, PJ ; Huan, T ; Hofman, Bert ; Uitterlinden, André ; Rivadeneira, Fernando ; van Rooij, J ; Stolk, Lisette ; Broer, Linda ; Verbiest, Michael ; Jhamai, M ; Arp, Pascal ; Metspalu, A ; Tserel, L ; Milani, L ; Samani, NJ ; Peterson, P ; Kasela, S ; Codd, V ; Peters, A ; Ward-Caviness, CK ; Herder, Cindy ; Waldenberger, M ; Roden, M ; Singmann, P ; Zeilinger, S ; Illig, T ; Homuth, G ; Grabe, HJ ; Voelzke, 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 (Eline) ; 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, Jiaqi ; Franke, L ; Kettunen, J ; Visscher, PM ; Neely, GG ; Korstanje, R ; Hanson, RL ; Prokisch, H ; Ferrucci, L ; Esko, T ; Teumer, A ; van Meurs, Joyce ; Andrew, D. / 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 = "Marjolein Peters and R Joehanes and LC Pilling and C Schurmann and KN Conneely and J Powell and E Reinmaa and GL Sutphin and A Zhernakova and K Schramm and YA Wilson and S Kobes and T Tukiainen and YF Ramos and HHH Goring and M Fornage and YM Liu and SA Gharib and BE Stranger and {De Jager}, PL and A Aviv and D Levy and JM Murabito and PJ Munson and T Huan and Bert Hofman and Andr{\'e} Uitterlinden and Fernando Rivadeneira and {van Rooij}, J and Lisette Stolk and Linda Broer and Michael Verbiest and M Jhamai and Pascal Arp and A Metspalu and L Tserel and L Milani and NJ Samani and P Peterson and S Kasela and V Codd and A Peters and CK Ward-Caviness and Cindy Herder and M Waldenberger and M Roden and P Singmann and S Zeilinger and T Illig and G Homuth and HJ Grabe and H Voelzke and L Steil and T Kocher and A Murray and D Melzer and H Yaghootkar and S Bandinelli and EK Moses and JW Kent and JE Curran and MP Johnson and S Williams-Blangero and HJ Westra and AF Mcrae and JA Smith and SLR Kardia and I Hovatta and M Perola and S Ripatti and V Salomaa and AK Henders and NG Martin and AK Smith and D Mehta and EB Binder and KM Nylocks and EM Kennedy and T Klengel and J Ding and AM Suchy-Dicey and DA Enquobahrie and J Brody and JI Rotter and YDI Chen and J Houwing-Duistermaat and M Kloppenburg and Slagboom, {PE (Eline)} and Q Helmer and {den Hollander}, W and S Bean and T Raj and N Bakhshi and QP Wang and LJ Oyston and BM Psaty and RP Tracy and GW Montgomery and ST Turner and J Blangero and I Meulenbelt and KJ Ressler and Jiaqi Yang and L Franke and J Kettunen and PM Visscher and GG Neely and R Korstanje and RL Hanson and H Prokisch and L Ferrucci and T Esko and A Teumer and {van Meurs}, Joyce and D Andrew",

year = "2015",

doi = "10.1038/ncomms9570",

language = "Undefined/Unknown",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Peters, M, 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, Goring, HHH, Fornage, M, Liu, YM, Gharib, SA, Stranger, BE, De Jager, PL, Aviv, A, Levy, D, Murabito, JM, Munson, PJ, Huan, T, Hofman, B , Uitterlinden, A , Rivadeneira, F, van Rooij, J, Stolk, L, Broer, L , Verbiest, M, 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, Voelzke, 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, J & Andrew, D 2015, 'The transcriptional landscape of age in human peripheral blood', Nature Communications, vol. 6. https://doi.org/10.1038/ncomms9570

The transcriptional landscape of age in human peripheral blood. / Peters, Marjolein; 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; Goring, HHH; Fornage, M; Liu, YM; Gharib, SA; Stranger, BE; De Jager, PL; Aviv, A; Levy, D; Murabito, JM; Munson, PJ; Huan, T; Hofman, Bert ; Uitterlinden, André ; Rivadeneira, Fernando; van Rooij, J; Stolk, Lisette; Broer, Linda ; Verbiest, Michael; Jhamai, M; Arp, Pascal; Metspalu, A; Tserel, L; Milani, L; Samani, NJ; Peterson, P; Kasela, S; Codd, V; Peters, A; Ward-Caviness, CK; Herder, Cindy; Waldenberger, M; Roden, M; Singmann, P; Zeilinger, S; Illig, T; Homuth, G; Grabe, HJ; Voelzke, 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 (Eline); 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, Jiaqi; Franke, L; Kettunen, J; Visscher, PM; Neely, GG; Korstanje, R; Hanson, RL; Prokisch, H; Ferrucci, L; Esko, T; Teumer, A; van Meurs, Joyce; Andrew, D.

In: Nature Communications, Vol. 6, 2015.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - The transcriptional landscape of age in human peripheral blood

AU - Peters, Marjolein

AU - Joehanes, R

AU - Pilling, LC

AU - Schurmann, C

AU - Conneely, KN

AU - Powell, J

AU - Reinmaa, E

AU - Sutphin, GL

AU - Zhernakova, A

AU - Schramm, K

AU - Wilson, YA

AU - Kobes, S

AU - Tukiainen, T

AU - Ramos, YF

AU - Goring, HHH

AU - Fornage, M

AU - Liu, YM

AU - Gharib, SA

AU - Stranger, BE

AU - De Jager, PL

AU - Aviv, A

AU - Levy, D

AU - Murabito, JM

AU - Munson, PJ

AU - Huan, T

AU - Hofman, Bert

AU - Uitterlinden, André

AU - Rivadeneira, Fernando

AU - van Rooij, J

AU - Stolk, Lisette

AU - Broer, Linda

AU - Verbiest, Michael

AU - Jhamai, M

AU - Arp, Pascal

AU - Metspalu, A

AU - Tserel, L

AU - Milani, L

AU - Samani, NJ

AU - Peterson, P

AU - Kasela, S

AU - Codd, V

AU - Peters, A

AU - Ward-Caviness, CK

AU - Herder, Cindy

AU - Waldenberger, M

AU - Roden, M

AU - Singmann, P

AU - Zeilinger, S

AU - Illig, T

AU - Homuth, G

AU - Grabe, HJ

AU - Voelzke, H

AU - Steil, L

AU - Kocher, T

AU - Murray, A

AU - Melzer, D

AU - Yaghootkar, H

AU - Bandinelli, S

AU - Moses, EK

AU - Kent, JW

AU - Curran, JE

AU - Johnson, MP

AU - Williams-Blangero, S

AU - Westra, HJ

AU - Mcrae, AF

AU - Smith, JA

AU - Kardia, SLR

AU - Hovatta, I

AU - Perola, M

AU - Ripatti, S

AU - Salomaa, V

AU - Henders, AK

AU - Martin, NG

AU - Smith, AK

AU - Mehta, D

AU - Binder, EB

AU - Nylocks, KM

AU - Kennedy, EM

AU - Klengel, T

AU - Ding, J

AU - Suchy-Dicey, AM

AU - Enquobahrie, DA

AU - Brody, J

AU - Rotter, JI

AU - Chen, YDI

AU - Houwing-Duistermaat, J

AU - Kloppenburg, M

AU - Slagboom, PE (Eline)

AU - Helmer, Q

AU - den Hollander, W

AU - Bean, S

AU - Raj, T

AU - Bakhshi, N

AU - Wang, QP

AU - Oyston, LJ

AU - Psaty, BM

AU - Tracy, RP

AU - Montgomery, GW

AU - Turner, ST

AU - Blangero, J

AU - Meulenbelt, I

AU - Ressler, KJ

AU - Yang, Jiaqi

AU - Franke, L

AU - Kettunen, J

AU - Visscher, PM

AU - Neely, GG

AU - Korstanje, R

AU - Hanson, RL

AU - Prokisch, H

AU - Ferrucci, L

AU - Esko, T

AU - Teumer, A

AU - van Meurs, Joyce

AU - Andrew, D

PY - 2015

Y1 - 2015

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.

U2 - 10.1038/ncomms9570

DO - 10.1038/ncomms9570

M3 - Article

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -