Exploring Trans-acting regulators of gene expression associated with metabolic syndrome: a coupled application of factor analysis and linkage analysis

Abstract

Metabolic syndrome is an established public health problem because it increases the risk of cardiovascular disease. Although many genes contribute to the etiology of metabolic syndrome, the effect size of each gene is much weaker than predicted by heritability. Exploring the regulation of gene expression levels can bridge this gap. Here, we aimed to explore genomic loci for a trans-regulator of gene expression associated with metabolic syndrome via factor analysis and linkage analysis. Forty-nine gene-expression quantitative traits (eQTs) associated with metabolic syndrome were selected and clustered into three latent eQTs by factor analysis. These included insulin-related, lipid-related, and glucose-related latent eQTs. Linkage analyses were performed for 49 original eQTs and 3 latent eQTs. Two original eQTs, adipose differentiation-related protein and IRS2, showed the highest LOD scores (3.09 and 3.08, respectively). We observed that the insulin-related and the lipid-related latent eQTs had stronger linkage evidence than the original eQTs, suggesting the presence of common gene regulators captured as latent eQTs. Several single nucleotide polymorphism markers located on the peaks were co-localized with specific genes. Five of them were related to the neuronal system, which plays a role in the metabolic syndrome pathway. The findings related those eQTs could contribute to our understanding regarding the genetic pathway for insulin and lipid metabolism, particularly the regulation of gene expression.