Unveiling Promising Drug Targets for NAFLD through Mendelian Randomization

Objectives Non-alcoholic fatty liver disease (NAFLD) is a common disorder that with genetic factors and few available treatments. The identification of new drug targets for NAFLD prevention remains a critical requirement. Methods In this study, we used Mendelian randomization analysis with summary statistics of NAFLD to investigate potential therapeutic targets. For this task, genetic tools obtained from a recent study that analyzed plasma proteins across nine groups were used. Improving the strength of Mendelian randomization findings can be achieved using two-sample Mendelian randomization analysis, Bayesian colocalization, steiger filter analysis, protein variation assessment, and mapping of expression quantitative trait loci to protein quantitative trait loci. Our goal was to improve our understanding of NAFLD and discover potential opportunities for its treatment by studying protein interactions, pathway enrichment, and drug targets. Results In summary, genetically predicted levels of 13 proteins were found to be correlated with the risk of non-alcoholic fatty liver disease (NAFLD). Specifically, elevated levels of nine proteins (ADH1B, TOM1L1, MMP3, GALE, RAB14, SNRPF, ADH1B, SPATA9) and decreased levels of five proteins were associated with an increased susceptibility to NAFLD. Conclusions Our thorough examination indicated that genetically determined levels of various circulating proteins are associated with susceptibility to NAFLD. These results imply that targeting these proteins may hold promise as a therapeutic approach for NAFLD and warrants additional clinical scrutiny.