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Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors

Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors
Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors
Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were also associated with the early environment; MSI2 methylation (β = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 β = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (β = −1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old β = 0.026, p = 0.0025; 20 years old β = 0.027, p = 0.0029) and between generations (mother β = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.
DNA methylation, adiposity, adolescence, body Composition, body mass index, epigenetic Variation, high-sensitivity C-reactive Protein, inflammation, leptin, maternal, the Raine Study, youth
1559-2294
Huang, R.C.
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Melton, P.E.
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Burton, M.A.
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Beilin, L.J.
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Clarke-Harris, R.
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Cook, E.
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Godfrey, K.M.
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Burdge, G.C.
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Mori, T.A.
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Anderson, D
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Rauschert, S.
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Craig, J.M.
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Kobor, M.S.
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MacIsaac, J.L.
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Morin, A.M.
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Oddy, W.H.
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Pennell, C.E.
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Holbrook, J.D.
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Lillycrop, K.A.
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Huang, R.C.
77f83e65-a6d3-4ea2-a032-0ea924fc4920
Melton, P.E.
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Burton, M.A.
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Beilin, L.J.
7728e5b8-3049-4273-bb16-d4f95088d91a
Clarke-Harris, R.
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Cook, E.
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Godfrey, K.M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Burdge, G.C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Mori, T.A.
9e47710e-412b-4633-9481-5a335890de41
Anderson, D
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Rauschert, S.
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Craig, J.M.
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Kobor, M.S.
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MacIsaac, J.L.
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Morin, A.M.
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Oddy, W.H.
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Pennell, C.E.
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Holbrook, J.D.
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Lillycrop, K.A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc

Huang, R.C., Melton, P.E., Burton, M.A., Beilin, L.J., Clarke-Harris, R., Cook, E., Godfrey, K.M., Burdge, G.C., Mori, T.A., Anderson, D, Rauschert, S., Craig, J.M., Kobor, M.S., MacIsaac, J.L., Morin, A.M., Oddy, W.H., Pennell, C.E., Holbrook, J.D. and Lillycrop, K.A. (2021) Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors. Epigenetics. (doi:10.1080/15592294.2021.1876297).

Record type: Article

Abstract

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were also associated with the early environment; MSI2 methylation (β = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 β = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (β = −1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old β = 0.026, p = 0.0025; 20 years old β = 0.027, p = 0.0029) and between generations (mother β = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.

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More information

Accepted/In Press date: 4 January 2021
e-pub ahead of print date: 8 February 2021
Keywords: DNA methylation, adiposity, adolescence, body Composition, body mass index, epigenetic Variation, high-sensitivity C-reactive Protein, inflammation, leptin, maternal, the Raine Study, youth

Identifiers

Local EPrints ID: 446908
URI: http://eprints.soton.ac.uk/id/eprint/446908
ISSN: 1559-2294
PURE UUID: a045b1bf-a336-4b88-9ba9-9cedaa7ead02
ORCID for R. Clarke-Harris: ORCID iD orcid.org/0000-0002-6888-9518
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for G.C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for K.A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

Catalogue record

Date deposited: 26 Feb 2021 17:30
Last modified: 15 Apr 2021 01:43

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Contributors

Author: R.C. Huang
Author: P.E. Melton
Author: M.A. Burton
Author: L.J. Beilin
Author: R. Clarke-Harris ORCID iD
Author: E. Cook
Author: K.M. Godfrey ORCID iD
Author: G.C. Burdge ORCID iD
Author: T.A. Mori
Author: D Anderson
Author: S. Rauschert
Author: J.M. Craig
Author: M.S. Kobor
Author: J.L. MacIsaac
Author: A.M. Morin
Author: W.H. Oddy
Author: C.E. Pennell
Author: J.D. Holbrook
Author: K.A. Lillycrop ORCID iD

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