Examining the association between adiposity and DNA methylation: A systematic review and meta‐analysis

Abstract

Summary Obesity is associated with widespread differential DNA methylation (DNAm) patterns, though there have been limited overlap in the obesity‐associated cytosine–guanine nucleotide pair (CpG) sites that have been identified in the literature. We systematically searched four databases for studies published until January 2020. Eligible studies included cross‐sectional, longitudinal, or intervention studies examining adiposity and genome‐wide DNAm in non‐pregnant adults aged 18–75 in all tissue types. Study design and results were extracted in the descriptive review. Blood‐based DNAm results in body mass index (BMI) and waist circumference (WC) were meta‐analyzed using weighted sum of Z‐score meta‐analysis. Of the 10,548 studies identified, 46 studies were included in the systematic review with 18 and nine studies included in the meta‐analysis of BMI and WC, respectively. In the blood, 77 and four CpG sites were significant in three or more studies of BMI and WC, respectively. Using a genome‐wide threshold for significance, 52 blood‐based CpG sites were significantly associated with BMI. These sites have previously been associated with many obesity‐related diseases including type 2 diabetes, cardiovascular disease, Crohn's disease, and depression. Our study shows that DNAm at 52 CpG sites represent potential mediators of obesity‐associated chronic diseases and may be novel intervention or therapeutic targets to protect against obesity‐associated chronic diseases.

DNA methylation patterns reflect individual's lifestyle independent of obesity

“…Although this is widely acknowledged by the scientific community, the majority of epigenetic studies in regard to obesity, most of them conducted cross‐sectionally, still lack the inclusion of relevant lifestyle drivers. 48 Therefore, to the best of our knowledge, this is one of the few studies investigating the potential effects of lifestyle on the respective blood DNA methylation signatures. 49 Here, we calculated LS scores based on each individual's diet, PA, smoking and alcohol consumption within the LIFE‐Adult study from Germany.…”

“…Epigenetic markers are known to reflect environmental conditions and thereby are affected not only by genetic predisposition but also most strongly by our daily lifestyle. Although this is widely acknowledged by the scientific community, the majority of epigenetic studies in regard to obesity, most of them conducted cross‐sectionally, still lack the inclusion of relevant lifestyle drivers 48 . Therefore, to the best of our knowledge, this is one of the few studies investigating the potential effects of lifestyle on the respective blood DNA methylation signatures 49 .…”

Human blood DNA methylation patterns reflect individual lifestyle

“…Epigenetic markers are known to reflect environmental conditions and thereby are not only affected by genetic predisposition, but most strongly by our daily lifestyle. Although this is widely acknowledged by the scientific community, the majority of epigenetic studies in regard to obesity, most of them conducted cross-sectionally, are still lacking the inclusion of relevant lifestyle drivers 45 . Therefore, to the best of our knowledge, this is one of the few studies investigating potential effects of lifestyle on the respective blood DNA methylation signatures 46 .…”

The potential of DNA methylation as a biomarker for obesity and smoking

“…To date, a few studies have investigated the epigenetic landscape in human obesity and weight loss in blood (reviewed by Ling C and Rönn [70] and Do [71], and Samblas et al [72] and Aronica et al [73], respectively). Some molecular pathways and genes, which could be prioritized when developing novel epigenetic biomarkers for obesity, have systematically been identified (Fig.…”