The Core Application and Practical Value of Mendelian Randomisation in Drug Target Research

Abstract

Mendelian randomisatio (MR) has demonstrated critical practical value in drug target research as a causal inference tool leveraging genetic variation. By employing genetic variation as an instrumental variable to simulate randomised controlled trials, MR circumvents confounding factors and reverse causality issues inherent in traditional observational studies, providing low-cost, highly reliable evidence for drug target development. This systematic review examines the current application of MR across three core domains: drug target identification and validation, drug repurposing, and safety assessment. Through exemplary cases in cardiovascular disease, metabolic disorders, and neurodegenerative diseases, it elucidates MR's mechanisms and practical outcomes in screening potential drug targets, expanding indications for existing drugs, and providing early warnings of drug safety risks. Concurrently, it analyses MR's unique advantages and challenges within these core applications, offering methodological guidance for future research. By 2025, MR had facilitated the validation of 18 drug targets progressing to Phase II/III clinical trials and driven the expansion of new indications for three classes of existing drugs, significantly enhancing clinical development success rates. This review aims to provide drug development practitioners with a comprehensive overview of MR's core applications, highlighting its pivotal role as a bridge between fundamental research and clinical translation.