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. 2017 Oct 30;7(1):14349.
doi: 10.1038/s41598-017-13099-4.

DNA-Methylation and Body Composition in Preschool Children: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study

Peter Rzehak  1 , Marcela Covic  2 , Richard Saffery  3 , Eva Reischl  4 , Simone Wahl  4 , Veit Grote  2 , Martina Weber  2 , Annick Xhonneux  5 , Jean-Paul Langhendries  5 , Natalia Ferre  6 , Ricardo Closa-Monasterolo  6 , Joaquin Escribano  6 , Elvira Verduci  7 , Enrica Riva  7 , Piotr Socha  8 , Dariusz Gruszfeld  8 , Berthold Koletzko  2
Affiliations

DNA-Methylation and Body Composition in Preschool Children: Epigenome-Wide-Analysis in the European Childhood Obesity Project (CHOP)-Study

Peter Rzehak et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Manhattan plot of all HM450K probe P-values for the association of BMI (kg/m2) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 2
Figure 2
Manhattan plot of all HM450K probe P-values for the association of WHO-standardised BMI (z-score) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 3
Figure 3
Manhattan plot of all HM450K probe P-values for the association of FM (kg) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 4
Figure 4
Manhattan plot of all HM450K probe P-values for the association of FMI (kg/m2) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 5
Figure 5
Manhattan plot of all HM450K probe P-values for the association of FFM (kg) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 6
Figure 6
Manhattan plot of all HM450K probe P-values for the association of FFMI (kg/m2) and methylation sites in preschool children. Top 10 sites are annotated. Red line indicates Bonferroni genome-wide significance and the blue line FDR significance. Chromosomal location of all HM450K probes is listed on the x-axis.
Figure 7
Figure 7
Overlap of differentially methylated probes (DMPs) associated with BMI, FMI and FFMI (a) and with FM and FFM (b) in preschool children. A full list of DMPs is provided in Supplementary Tables S1 to S6. Genes in brackets indicate manual annotation for closest genes using the UCSC genome browser on human GRCh37/hg19 assembly.
See this image and copyright information in PMC

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