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Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors
Citation
Huang, RC and Melton, PE and Burton, MA and Beilin, LJ and Clarke-Harris, R and Cook, E and Godfrey, KM and Burdge, E and Mori, TA and Anderson, D and Rauschert, S and Craig, JM and Kobor, MS and MacIsaac, JL and Morin, AM and Oddy, WH and Pennell, CE and Holbrook, JD and Lillycrop, KA, Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors, Epigenetics pp. 1-18. ISSN 1559-2294 (2021) [Refereed Article]
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Copyright Statement
Copyright 2021 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
DOI: doi:10.1080/15592294.2021.1876297
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | DNA methylation, adiposity, adolescence, body composition, body mass index, epigenetic variation, high-sensitivity C-reactive Protein, inflammation, leptin |
| Research Division: | Biological Sciences |
| Research Group: | Genetics |
| Research Field: | Epigenetics (incl. genome methylation and epigenomics) |
| Objective Division: | Health |
| Objective Group: | Specific population health (excl. Indigenous health) |
| Objective Field: | Adolescent health |
| UTAS Author: | Melton, PE (Dr Phillip Melton) |
| UTAS Author: | Oddy, WH (Professor Wendy Oddy) |
| ID Code: | 144691 |
| Year Published: | 2021 |
| Web of Science® Times Cited: | 6 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2021-06-04 |
| Last Modified: | 2022-08-25 |
| Downloads: | 11 View Download Statistics |
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