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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 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
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-06-04
Last Modified:2021-08-04
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