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PGC1α promoter methylation in blood at 5–7 years predicts adiposity from 9 to 14 years (EarlyBird 50)

PGC1α promoter methylation in blood at 5–7 years predicts adiposity from 9 to 14 years (EarlyBird 50)
PGC1α promoter methylation in blood at 5–7 years predicts adiposity from 9 to 14 years (EarlyBird 50)
The early environment, acting via epigenetic processes, is associated with differential risk of cardio-metabolic disease (CMD) which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analysed DNA methylation in the peroxisomal proliferator-?-co-activator-1? promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years by pyrosequencing. Body composition was measured annually by dual x-ray absorptiometry, physical activity by accelerometery and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven CpG loci were identified that showed no significant temporal change or association with leukocyte populations. Modelling using generalised estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing and activity. Methylation of one predictive locus modified binding of the pro-adipogenic PBX-1/HOXB9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.
0012-1797
2528-2537
Clarke-Harris, Rebecca
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Wilkin, Terrence
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Hosking, Joanna
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Pinkney, Jonathan
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Jeffery, Alison
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Metcalf, Brad
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Godfrey, Keith
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Voss, Linda
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Lillycrop, Karen
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Burdge, Graham
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Clarke-Harris, Rebecca
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Wilkin, Terrence
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Hosking, Joanna
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Pinkney, Jonathan
412d6268-047d-4979-8586-14e3286fad48
Jeffery, Alison
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Metcalf, Brad
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Godfrey, Keith
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Voss, Linda
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Lillycrop, Karen
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Burdge, Graham
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Clarke-Harris, Rebecca, Wilkin, Terrence, Hosking, Joanna, Pinkney, Jonathan, Jeffery, Alison, Metcalf, Brad, Godfrey, Keith, Voss, Linda, Lillycrop, Karen and Burdge, Graham (2014) PGC1α promoter methylation in blood at 5–7 years predicts adiposity from 9 to 14 years (EarlyBird 50). Diabetes, 63 (7), 2528-2537. (doi:10.2337/db13-0671). (PMID:24622795)

Record type: Article

Abstract

The early environment, acting via epigenetic processes, is associated with differential risk of cardio-metabolic disease (CMD) which can be predicted by epigenetic marks in proxy tissues. However, such measurements at time points disparate from the health outcome or the environmental exposure may be confounded by intervening stochastic and environmental variation. To address this, we analysed DNA methylation in the peroxisomal proliferator-?-co-activator-1? promoter in blood from 40 children (20 boys) collected annually between 5 and 14 years by pyrosequencing. Body composition was measured annually by dual x-ray absorptiometry, physical activity by accelerometery and pubertal timing by age at peak high velocity. The effect of methylation on transcription factor binding was investigated by electrophoretic mobility shift assays. Seven CpG loci were identified that showed no significant temporal change or association with leukocyte populations. Modelling using generalised estimating equations showed that methylation of four loci predicted adiposity up to 14 years independent of sex, age, pubertal timing and activity. Methylation of one predictive locus modified binding of the pro-adipogenic PBX-1/HOXB9 complex. These findings suggest that temporally stable CpG loci measured in childhood may have utility in predicting CMD risk.

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e-pub ahead of print date: March 2014
Published date: 12 July 2014
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 365681
URI: http://eprints.soton.ac.uk/id/eprint/365681
ISSN: 0012-1797
PURE UUID: 33936e92-a075-4f85-bb53-77a10148db81
ORCID for Rebecca Clarke-Harris: ORCID iD orcid.org/0000-0002-6888-9518
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Graham Burdge: ORCID iD orcid.org/0000-0002-7665-2967

Catalogue record

Date deposited: 13 Jun 2014 12:19
Last modified: 13 Nov 2021 02:48

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Contributors

Author: Rebecca Clarke-Harris ORCID iD
Author: Terrence Wilkin
Author: Joanna Hosking
Author: Jonathan Pinkney
Author: Alison Jeffery
Author: Brad Metcalf
Author: Keith Godfrey ORCID iD
Author: Linda Voss
Author: Karen Lillycrop ORCID iD
Author: Graham Burdge ORCID iD

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