Abstract
Epigenetic signatures such as DNA methylation may be associated with specific obesity traits in different tissues. The onset and development of some obesity-related complications are often linked to visceral fat accumulation. The aim of this study was to explore DNA methylation levels in peripheral white blood cells to identify epigenetic methylation marks associated with waist circumference (WC). DNA methylation levels were assessed using Infinium Human Methylation 450K and MethylationEPIC beadchip (Illumina) to search for putative associations with WC values of 473 participants from the Methyl Epigenome Network Association (MENA) project. Statistical analysis and Ingenuity Pathway Analysis (IPA) were employed for assessing the relationship between methylation and WC. A total of 669 CpGs were statistically associated with WC (FDR < 0.05, slope ≥ |0.1|). From these CpGs, 375 CpGs evidenced a differential methylation pattern between females with WC ≤ 88 and > 88 cm, and 95 CpGs between males with WC ≤ 102 and > 102 cm. These differentially methylated CpGs are located in genes related to inflammation and obesity according to IPA. Receiver operating characteristic (ROC) curves of the top four significant differentially methylated CpGs separated by sex discriminated individuals with presence or absence of abdominal fat. ROC curves of all the CpGs from females and one CpG from males were validated in an independent sample (n = 161). These methylation results add further insights about the relationships between obesity, adiposity-associated comorbidities, and DNA methylation where inflammation processes may be involved.
Highlights
Obesity has increased worldwide to reach epidemic proportions [1]
waist circumference (WC) values showed a higher number of individuals from both sexes with central adiposity, it depends on the study
This study involving the Methyl Epigenome Network Association (MENA) project reports the association between DNA methylation and WC
Summary
Obesity has increased worldwide to reach epidemic proportions [1]. According to the WorldHealth Organization, the prevalence of obesity nearly doubled between 1980 and 2014, reaching an alarming percentage of 11% in men and 15% in women worldwide [2]. Genes 2019, 10, 444 diseases, diabetes, cancer, and musculoskeletal disorders, among others [2] The development of these obesity-related complications are more often associated with visceral fat instead of total body fat [3]. Several epigenome-wide association studies (EWASs) have revealed that obesity traits are associated with DNA methylation shifts in different tissues [6,8,9] Most of these studies use body mass index (BMI) instead of WC, but WC appears to be a more accurate and convenient surrogate for central obesity assessment [4], being more associated with obesity-related diseases [3]. There are only few EWAS analyzing the association of methylation status and WC [10,11,12,13,14,15,16]
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