Mendelian randomization for studying the effects of perturbing drug targets

Abstract

Drugs whose targets have genetic evidence to support efficacy and safety are more likely to be approved after clinical development. In this paper, we provide an overview of how natural sequence variation in the genes that encode drug targets can be used in Mendelian randomization analyses to offer insight into mechanism-based efficacy and adverse effects. Large databases of summary level genetic association data are increasingly available and can be leveraged to identify and validate variants that serve as proxies for drug target perturbation. As with all empirical research, Mendelian randomization has limitations including genetic confounding, its consideration of lifelong effects, and issues related to heterogeneity across different tissues and populations. When appropriately applied, Mendelian randomization provides a useful empirical framework for using population level data to improve the success rates of the drug development pipeline.

Cited by papers we hold 4

• Using genetic association data to guide drug discovery and development: Review of methods and applications · 2023
  No notice
• Mendelian randomization for cardiovascular diseases: principles and applications · 2023
  No notice
• Therapeutic potential of IL6R blockade for the treatment of sepsis and sepsis-related death: A Mendelian randomisation study · 2023
  No notice
• Statistical methods for cis ‐Mendelian randomization with two‐sample summary‐level data · 2022
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.