Unveiling functionality and conducting two-sample mendelian randomization on WGCNA-identified oxidative stress-related hub genes in metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease (MAFLD) shows accelerated development under the impact of oxidative stress (OS). There is an imperative to identify OS-related biomarkers in MAFLD and explore their potential mechanistic insights. The objective of this study was to identify OS-related biomarkers in MAFLD and explore their potential mechanisms. DEG analysis was performed using GSE17470 and GSE24807 datasets. An investigative exploration utilizing WGCNA was executed to elucidate hub OS-related genes. The intersection of OS-related hub genes identified by WGCNA and DEGs was systematically employed for thorough analyses. A mendelian randomization (MR) study examined the causal effect of C-reactive protein (CRP) on MAFLD. 59 OS-related DEGs were identified in MAFLD. WGCNA revealed 100 OS-related hub genes in MAFLD. Sixteen OS-related genes have been delineated as critical components in MAFLD. Enrichment analyses, employing GO and KEGG pathways, revealed pathways enriched with these genes. Following PPI analyses, the highest-ranking ten hub genes demonstrating abnormal expression were determined. Ultimately, a two-sample MR analysis demonstrated a causal link between the hub gene CRP and the occurrence of MAFLD. In this study, we harnessed WGCNA to formulate a co-expression network and identified hub OS-related DEGs in MAFLD. Additionally, the hub gene CRP exhibited a significant correlation with the predisposition to MAFLD. These findings offer innovative perspectives on the applications of OS-associated genes in individuals afflicted with MAFLD.