Differentially expressed genes and therapeutic targets for nonalcoholic fatty liver disease from transcriptomic techniques

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. Lifestyle interventions are currently available as the main treatment modality. However, there is an urgent need to develop new therapeutic approaches for NAFLD owing to its complex pathological mechanisms. This study aimed to reveal potential therapeutic targets for NAFLD through molecular mechanism analysis. Using publicly available microarray datasets, we performed differentially expressed gene analysis to identify gene expression changes in NAFLD samples relative to healthy ones. Subsequently, expression-quantitative trait loci (eQTL) and Mendelian randomization (MR) analyses were applied to evaluate the relationship between these genes and NAFLD. Additionally, the potential functional pathways of differentially expressed genes were explored using enrichment analyses. A variety of differentially expressed genes are significantly up- or down-regulated in NAFLD samples. eQTL and MR analyses confirmed the causal relationship between some key genes and NAFLD. Enrichment analysis revealed that these genes are mainly associated with key signaling pathways, including inflammatory and immune responses, indicating that these pathways significantly contribute to the pathophysiology of NAFLD. This study revealed crucial genes and signaling pathways in NAFLD through multi-level bioinformatics and MR analysis, providing new insights for future treatments. The results underscore the necessity of comprehending NAFLD's intricate pathobiology to facilitate the development of innovative therapies, alleviate the burden on patients and society, and improve public health.