Abstract
Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes. Few Epigenome-Wide-Association-Studies have identified DNA-methylation (DNAm) signatures associated with BMI and body composition in children. Body composition by Bio-Impedance-Analysis and genome-wide DNAm in whole blood were assessed in 374 pre-school children from four European countries. Associations were tested by linear regression adjusted for sex, age, centre, education, 6 WBC-proportions according to Houseman and 30 principal components derived from control probes. Specific DNAm variants were identified to be associated with BMI (212), fat-mass (230), fat-free-mass (120), fat-mass-index (24) and fat-free-mass-index (15). Probes in genes SNED1(IRE-BP1), KLHL6, WDR51A(POC1A), CYTH4-ELFN2, CFLAR, PRDM14, SOS1, ZNF643(ZFP69B), ST6GAL1, C3orf70, CILP2, MLLT4 and ncRNA LOC101929268 remained significantly associated after Bonferroni-correction of P-values. We provide novel evidence linking DNAm with (i) altered lipid and glucose metabolism, (ii) diabetes and (iii) body size and composition in children. Both common and specific epigenetic signatures among measures were also revealed. The causal direction with phenotypic measures and stability of DNAm variants throughout the life course remains unclear and longitudinal analysis in other populations is required. These findings give support for potential epigenetic programming of body composition and obesity.
Highlights
Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes
In this study of peripheral blood from 374 European pre-school children with highly accurate measures of body composition, we identified 212 differentially methylated probes (DMPs) associated with body mass index (BMI), 230 DMPs with Fat mass (FM), 120 DMPs with Fat free mass (FFM), 24 DMPs with FMI and 15 DMPs with FFMI
These probes measure DNAm in CpG sites that generally reside in protein-coding genes and non-coding RNAs previously linked with inflammation, glucose and lipid metabolism, browning of white fat, obesity and diabetes
Summary
Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes. We provide novel evidence linking DNAm with (i) altered lipid and glucose metabolism, (ii) diabetes and (iii) body size and composition in children. Both common and specific epigenetic signatures among measures were revealed. The causal direction with phenotypic measures and stability of DNAm variants throughout the life course remains unclear and longitudinal analysis in other populations is required. These findings give support for potential epigenetic programming of body composition and obesity. Aetiologies of metabolic dysregulation that begin early in life in response to genetic and environmental (including nutritional) factors and are potentially mediated by epigenetic mechanisms over the life course[3,4,5,6,7,8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
