Abstract: Variability in plasma carotenoids may be attributable to several factors including genetic
variants and lipid profile. Until now, the impact of DNA methylation on this variability has not
been widely studied. Weighted gene correlation network analysis (WGCNA) is a systems biology
method used for finding gene clusters (modules) with highly correlated methylation levels and for
relating them to phenotypic traits. The objective of the present study was to examine the role of DNA
methylation in the relationship between plasma total carotenoid concentrations and lipid profile
using WGCNA in 48 healthy subjects. Genome-wide DNA methylation levels of 20,687 out of 472,245
CpG sites in blood leukocytes were associated with total carotenoid concentrations. Using WGCNA,
nine co-methylation modules were identified. A total of 2734 hub genes (17 unique top hub genes)
were potentially related to lipid profile. This study provides evidence for the potential implications
of gene co-methylation in the relationship between plasma carotenoids and lipid profile. Further
studies and validation of the hub genes are needed
