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The current study was designed to use an epigenome-wide association approach (EWAS) to identify potential systemic DNA methylation alterations that are associated with obesity using 22 discordant twin pairs. Buccal cells (from a cheek swab) were used as a non-obesity relevant purified marker cell for the epigenetic analysis. Analysis of differential DNA methylation regions (DMRs) was used to identify epigenetic associations with metabolic and dietary measures related to obesity with discordant twins. An edgeR analysis provided a DMR signature with  p  &lt; 1e-04, but statistical significance was reduced due to low sample size and known multiple origins of obesity. A weighted gene coexpression network analysis (WGCNA) was performed and identified modules ( p  &lt; 0.005) of epigenetic sites that correlated with different metabolic and dietary measures. The DMR and WGCNA epigenetic sites were near genes (e.g., CIDEC, SPP1, ZFPG9, and POMC) with previously identified obesity associated pathways (e.g., metabolism, cholesterol, and fat digestion). Observations demonstrate the feasibility of identifying systemic epigenetic biomarkers for obesity, which can be further investigated for clinical relevance in future research with larger sample sizes. The availability of a systemic epigenetic biomarker for obesity susceptibility may facilitate preventative medicine and clinical management of the disease early in life.

Epigenome-wide association study of systemic effects of obesity susceptibility in human twins