Background: Little is currently known about epigenetic alterations associated with body composition in obesity. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and three common traits of body composition as measured by body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) among Chinese monozygotic twins.
Methods: Generalized estimated equation model was used to regress the methylation level of CpG sites on body composition. Inference about Causation Through Examination Of Familial Confounding was used to explore the evidence of a causal relationship. Gene expression analysis was further performed to validate the results of differentially methylated genes.
Results: We identified 32, 22 and 28 differentially methylated CpG sites (p < 10-5 ) as well as 20, 17 and eight differentially methylated regions (slk-corrected p < 0.05) significantly associated with BF%, FM and LBM which were annotated to 65 genes, showing partially overlapping. Causal inference demonstrated bidirectional causality between DNA methylation and body composition (p < 0.05). Gene expression analysis revealed significant correlations between expression levels of five differentially methylated genes and body composition (p < 0.05).
Conclusions: These DNA methylation signatures will contribute to increased knowledge about the epigenetic basis of body composition and provide new strategies for early prevention and treatment of obesity and its related diseases.
Keywords: DNA methylation; body composition; epigenome-wide association study; twin study.
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