Associations Between Obstructive Sleep Apnea and Metabolic Dysfunction-Associated Fatty Liver Disease: Insights from...

Area of Science:

• Genetics and Bioinformatics
• Metabolic and Liver Diseases
• Sleep Medicine

Background:

• Obstructive sleep apnea (OSA) is associated with metabolic dysfunction-associated fatty liver disease (MAFLD).
• The precise causal links and molecular mechanisms connecting OSA and MAFLD are not fully understood.
• Investigating shared biomarkers is crucial for understanding their relationship.

Purpose of the Study:

• To investigate the causal association between OSA and MAFLD.
• To explore the mediating role of body mass index (BMI) in this relationship.
• To identify shared biomarkers and underlying mechanisms using Mendelian randomization and bioinformatics.

Main Methods:

• Utilized two-sample and network Mendelian randomization (MR) with genome-wide association study (GWAS) data for OSA and MAFLD.
• Employed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify intersection genes.
• Conducted functional enrichment (GO, KEGG), protein-protein interaction (PPI) network, and immune cell infiltration analyses (ssGSEA).

Main Results:

• MR analysis indicated that OSA significantly increases MAFLD risk (OR=1.40, p=0.002).
• OSA mediated 62.3% of the effect of BMI on MAFLD.
• Identified 42 intersection genes, with four hub genes (FOS, EGR1, NR4A1, JUN) linked to immune cell infiltration; three immune cell phenotypes were associated with both diseases.

Conclusions:

• Obstructive sleep apnea has a causal influence on MAFLD.
• OSA acts as a mediator for the effect of BMI on MAFLD.
• Key genes and immune cell phenotypes are implicated in the shared pathogenesis of OSA and MAFLD.