Metabolomic markers reveal novel pathways of ageing and early development in human populations

C. Menni, G. Kastenmüller, A.K. Petersen, J.T. Bell, M. Psatha, P.-C. Tsai, C. Gieger, H. Schulz, I. Erte, S. John, M.J. Brosnan, Scott Wilson, L. Tsaprouni, Ee Lim, Bronwyn Stuckey, P. Deloukas, R. Mohney, K. Suhre, T.D. Spector, A.M. Valdes

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Abstract

Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2=59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta=0.03, SE=0.001, P=7.0×10-157) and lung function (FEV1 beta=-0.04, SE=0.008, P=1.8×10-8 adjusted for age and confounders) and was replicated in an independent population (n=887). C-glyTrp was also associated with bone mineral density (beta=-0.01, SE=0.002, P=1.9×10-6) and birthweight (beta=-0.06, SE=0.01, P=2.5×10-9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P <2×10-6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta=-0.20, SE=0.04, P=2.9×10-8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing. © The Author 2013; All rights reserved.
Original languageEnglish
Pages (from-to)1111-1119
JournalInternational Journal of Epidemiology
Volume42
Issue number4
DOIs
Publication statusPublished - 2013

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Metabolomics
Human Development
Tryptophan
Monozygotic Twins
Population
Peptide Elongation Factor 2
Health
Eukaryota
Epigenomics
Bone Density
Methylation
Fasting
Genome
Lung
Genes
Proteins

Cite this

Menni, C., Kastenmüller, G., Petersen, A. K., Bell, J. T., Psatha, M., Tsai, P-C., ... Valdes, A. M. (2013). Metabolomic markers reveal novel pathways of ageing and early development in human populations. International Journal of Epidemiology, 42(4), 1111-1119. https://doi.org/10.1093/ije/dyt094
Menni, C. ; Kastenmüller, G. ; Petersen, A.K. ; Bell, J.T. ; Psatha, M. ; Tsai, P.-C. ; Gieger, C. ; Schulz, H. ; Erte, I. ; John, S. ; Brosnan, M.J. ; Wilson, Scott ; Tsaprouni, L. ; Lim, Ee ; Stuckey, Bronwyn ; Deloukas, P. ; Mohney, R. ; Suhre, K. ; Spector, T.D. ; Valdes, A.M. / Metabolomic markers reveal novel pathways of ageing and early development in human populations. In: International Journal of Epidemiology. 2013 ; Vol. 42, No. 4. pp. 1111-1119.
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author = "C. Menni and G. Kastenm{\"u}ller and A.K. Petersen and J.T. Bell and M. Psatha and P.-C. Tsai and C. Gieger and H. Schulz and I. Erte and S. John and M.J. Brosnan and Scott Wilson and L. Tsaprouni and Ee Lim and Bronwyn Stuckey and P. Deloukas and R. Mohney and K. Suhre and T.D. Spector and A.M. Valdes",
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Menni, C, Kastenmüller, G, Petersen, AK, Bell, JT, Psatha, M, Tsai, P-C, Gieger, C, Schulz, H, Erte, I, John, S, Brosnan, MJ, Wilson, S, Tsaprouni, L, Lim, E, Stuckey, B, Deloukas, P, Mohney, R, Suhre, K, Spector, TD & Valdes, AM 2013, 'Metabolomic markers reveal novel pathways of ageing and early development in human populations' International Journal of Epidemiology, vol. 42, no. 4, pp. 1111-1119. https://doi.org/10.1093/ije/dyt094

Metabolomic markers reveal novel pathways of ageing and early development in human populations. / Menni, C.; Kastenmüller, G.; Petersen, A.K.; Bell, J.T.; Psatha, M.; Tsai, P.-C.; Gieger, C.; Schulz, H.; Erte, I.; John, S.; Brosnan, M.J.; Wilson, Scott; Tsaprouni, L.; Lim, Ee; Stuckey, Bronwyn; Deloukas, P.; Mohney, R.; Suhre, K.; Spector, T.D.; Valdes, A.M.

In: International Journal of Epidemiology, Vol. 42, No. 4, 2013, p. 1111-1119.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolomic markers reveal novel pathways of ageing and early development in human populations

AU - Menni, C.

AU - Kastenmüller, G.

AU - Petersen, A.K.

AU - Bell, J.T.

AU - Psatha, M.

AU - Tsai, P.-C.

AU - Gieger, C.

AU - Schulz, H.

AU - Erte, I.

AU - John, S.

AU - Brosnan, M.J.

AU - Wilson, Scott

AU - Tsaprouni, L.

AU - Lim, Ee

AU - Stuckey, Bronwyn

AU - Deloukas, P.

AU - Mohney, R.

AU - Suhre, K.

AU - Spector, T.D.

AU - Valdes, A.M.

PY - 2013

Y1 - 2013

N2 - Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2=59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta=0.03, SE=0.001, P=7.0×10-157) and lung function (FEV1 beta=-0.04, SE=0.008, P=1.8×10-8 adjusted for age and confounders) and was replicated in an independent population (n=887). C-glyTrp was also associated with bone mineral density (beta=-0.01, SE=0.002, P=1.9×10-6) and birthweight (beta=-0.06, SE=0.01, P=2.5×10-9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P <2×10-6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta=-0.20, SE=0.04, P=2.9×10-8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing. © The Author 2013; All rights reserved.

AB - Background Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age. Methods Metabolomic profiling on fasting blood was carried out in 6055 individuals from the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels. Results We identified a panel of 22 metabolites which combined are strongly correlated with age (R2=59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta=0.03, SE=0.001, P=7.0×10-157) and lung function (FEV1 beta=-0.04, SE=0.008, P=1.8×10-8 adjusted for age and confounders) and was replicated in an independent population (n=887). C-glyTrp was also associated with bone mineral density (beta=-0.01, SE=0.002, P=1.9×10-6) and birthweight (beta=-0.06, SE=0.01, P=2.5×10-9). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P <2×10-6). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta=-0.20, SE=0.04, P=2.9×10-8). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes. Conclusions Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing. © The Author 2013; All rights reserved.

U2 - 10.1093/ije/dyt094

DO - 10.1093/ije/dyt094

M3 - Article

VL - 42

SP - 1111

EP - 1119

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 4

ER -