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 HumanMethylation 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