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

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.