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Genome-wide methylation analysis identifies differently methylated CpG loci associated with severe obesity in childhood

Genome-wide methylation analysis identifies differently methylated CpG loci associated with severe obesity in childhood
Genome-wide methylation analysis identifies differently methylated CpG loci associated with severe obesity in childhood
Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 – 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 – 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.
biomarkers, childhood obesity, epigenetics, genome-wide, methylation
1559-2294
995-1005
Huang, R.C.
77f83e65-a6d3-4ea2-a032-0ea924fc4920
Garratt, E.S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Pan, H.
c3e588e4-072e-4f05-802a-ab6d47d7358a
Wu, Y.
84854e37-ada6-4cc8-995f-6ce5ebc77423
Davies, E.A.
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Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Burdge, G.C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Holbrook, J.D.
070ac5b7-0f42-4425-994a-8135218212d7
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Huang, R.C.
77f83e65-a6d3-4ea2-a032-0ea924fc4920
Garratt, E.S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Pan, H.
c3e588e4-072e-4f05-802a-ab6d47d7358a
Wu, Y.
84854e37-ada6-4cc8-995f-6ce5ebc77423
Davies, E.A.
241a2fb2-6d05-4b6a-8804-b0532e9627f1
Barton, S.J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Burdge, G.C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Holbrook, J.D.
070ac5b7-0f42-4425-994a-8135218212d7
Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc

Huang, R.C., Garratt, E.S., Pan, H., Wu, Y., Davies, E.A., Barton, S.J., Burdge, G.C., Godfrey, K.M., Holbrook, J.D. and Lillycrop, K.A. (2015) Genome-wide methylation analysis identifies differently methylated CpG loci associated with severe obesity in childhood. Epigenetics, 10 (11), 995-1005. (doi:10.1080/15592294.2015.1080411). (PMID:26646899)

Record type: Article

Abstract

Childhood obesity is a major public health issue. Here we investigated whether differential DNA methylation was associated with childhood obesity. We studied DNA methylation profiles in whole blood from 78 obese children (mean BMI Z-score: 2.6) and 71 age- and sex-matched controls (mean BMI Z-score: 0.1). DNA samples from obese and control groups were pooled and analyzed using the Infinium HumanMethylation450 BeadChip array. Comparison of the methylation profiles between obese and control subjects revealed 129 differentially methylated CpG (DMCpG) loci associated with 80 unique genes that had a greater than 10% difference in methylation (P-value < 0.05). The top pathways enriched among the DMCpGs included developmental processes, immune system regulation, regulation of cell signaling, and small GTPase-mediated signal transduction. The associations between the methylation of selected DMCpGs with childhood obesity were validated using sodium bisulfite pyrosequencing across loci within the FYN, PIWIL4, and TAOK3 genes in individual subjects. Three CpG loci within FYN were hypermethylated in obese individuals (all P < 0.01), while obesity was associated with lower methylation of CpG loci within PIWIL4 (P = 0.003) and TAOK3 (P = 0.001). After building logistic regression models, we determined that a 1% increase in methylation in TAOK3, multiplicatively decreased the odds of being obese by 0.91 (95% CI: 0.86 – 0.97), and an increase of 1% methylation in FYN CpG3, multiplicatively increased the odds of being obese by 1.03 (95% CI: 0.99 – 1.07). In conclusion, these findings provide evidence that childhood obesity is associated with specific DNA methylation changes in whole blood, which may have utility as biomarkers of obesity risk.

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Accepted/In Press date: 1 August 2015
e-pub ahead of print date: 11 September 2015
Published date: 2 November 2015
Keywords: biomarkers, childhood obesity, epigenetics, genome-wide, methylation
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 385435
URI: http://eprints.soton.ac.uk/id/eprint/385435
ISSN: 1559-2294
PURE UUID: a02c7af1-5938-4b9e-afa9-e120fbc16e34
ORCID for E.S. Garratt: ORCID iD orcid.org/0000-0001-5268-4203
ORCID for S.J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for G.C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

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Date deposited: 19 Jan 2016 15:20
Last modified: 07 Oct 2020 01:46

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Contributors

Author: R.C. Huang
Author: E.S. Garratt ORCID iD
Author: H. Pan
Author: Y. Wu
Author: E.A. Davies
Author: S.J. Barton ORCID iD
Author: G.C. Burdge ORCID iD
Author: K.M. Godfrey ORCID iD
Author: J.D. Holbrook
Author: K.A. Lillycrop ORCID iD

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