Background: Cardiovascular diseases (CVDs) and their cardiometabolic comorbidities frequently co-occur and share risk factors, indicating common molecular mechanisms. However, these pathways remain poorly characterized at the transcriptomic level and are often studied separately.
Objective: To identify shared gene modules linking cardiometabolic traits and fatty liver disease through gene co-expression network analysis.
Materials and Methods: Data from the Young Finns Study (YFS), including gene expression profiles (25,950 genes) and clinical data from 993 individuals, were analyzed. A signed weighted gene co-expression network (WGCNA) was constructed to identify modules of co-expressed genes. Module–trait associations were evaluated using correlation analysis for cardiometabolic traits and logistic regression for fatty liver status, adjusting for age and sex. Differential expression analysis was performed on the full dataset, and pathway enrichment analysis was conducted for genes within significant modules.
Results: A signed co-expression network analysis identified 20 gene modules. Several modules showed significant associations with key cardiometabolic traits, including BMI, waist circumference, blood pressure, lipid levels, and glucose (FDR < 0.05). Six modules were significantly associated with fatty liver, with one module showing the strongest positive association (OR = 1.43, FDR = 1.47 × 10⁻³). Both positive and inverse associations were observed. Modules linked to fatty liver also showed consistent relationships with cardiometabolic traits, indicating shared transcriptomic patterns.
Conclusion: These findings reveal shared transcriptomic mechanisms linking cardiometabolic traits and fatty liver disease and highlight key molecular pathways for future investigation.

Co-authors: Terho Lehtimäki, Reija Autio, Juhani S. Koskinen, Nina Mononen, Mika Kähönen, Olli Raitakari, Pashupati P. Mishra, Binisha Hamal Mishra