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

Abstract

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.