Weighted gene co-expression network analysis to explain the relationship between plasma total carotenoids and lipid profile.

Background: Variability in circulating carotenoids may be attributable to several factors including, among others, genetic variants and lipid profile. However, relatively few studies have considered the impact of gene expression in the inter-individual variability in circulating carotenoids. Most studies considered expression of genes individually and ignored their high degree of interconnection. Weighted gene co-expression network analysis (WGCNA) is a systems biology method used for finding gene clusters with highly correlated expression levels and for relating them to phenotypic traits. The objective of the present observational study is to examine the relationship between plasma total carotenoid concentrations and lipid profile using WGCNA.

Results: Whole blood expression levels of 533 probes were associated with plasma total carotenoids. Among the four WGCNA distinct modules identified, turquoise, blue, and brown modules correlated with plasma high-density lipoprotein cholesterol (HDL-C) and total cholesterol. Probes showing a strong association with HDL-C and total cholesterol were also the most important elements of the brown and blue modules. A total of four and 29 hub genes associated with total carotenoids were potentially related to HDL-C and total cholesterol, respectively.

Conclusions: Expression levels of 533 probes were associated with plasma total carotenoid concentrations. Using WGCNA, four modules and several hub genes related to lipid and carotenoid metabolism were identified. This integrative analysis provides evidence for the potential role of gene co-expression in the relationship between carotenoids and lipid concentrations. Further studies and validation of the hub genes are needed.