Drug-target Mendelian randomisation leverages human genetics to facilitate the discovery, repositioning, and safety assessment of drug targets in MASLD.
Drug-target Mendelian randomisation offers a promising approach leveraging human genetics for discovering and repositioning drug targets in MASLD.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent cause of chronic liver disease worldwide affecting over one-third of the adult population. Despite the recent evolution of new nomenclature and diagnostic criteria for MASLD, progress in drug development for this condition remains limited. This review highlights the potential of drug-target Mendelian randomisation (MR), a study design that leverages human genetics and genomics, for the discovery, repositioning and safety assessment of drug targets in MASLD. We summarised key aspects of designing and appraising a drug-target MR study, discussing its inherent assumptions and considerations for instrument selection. Furthermore, we presented real-world examples from studies in MASLD which focused on opportunities and challenges in identifying novel drug targets, repositing existing drug targets, informing adjunctive treatments and addressing issues in paediatric MASLD.
Luo et al. (2024) studied this question. Drug-target Mendelian randomisation leverages human genetics to facilitate the discovery, repositioning, and safety assessment of drug targets in MASLD.