Mendelian randomization for studying the effects of perturbing drug targets

Dipender Gill*, Marios K Georgakis, Venexia M Walker, Amand Floriaan Schmidt, Apostolos Gkatzionis, Daniel F Freitag, Chris Finan, Aroon D Hingorani, Joanna M. M Howson, Stephen Burgess, Daniel I Swerdlow, George Davey Smith, Bruce M Psaty, Neil M Davies

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

61 Citations (Scopus)
94 Downloads (Pure)


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.
Original languageEnglish
Article number16
JournalWellcome Open Research
Publication statusPublished - 28 Feb 2021

Bibliographical note

Publisher Copyright:
© 2021 Gill D et al.


  • Drugs
  • Genetics
  • Mendelian randomization


Dive into the research topics of 'Mendelian randomization for studying the effects of perturbing drug targets'. Together they form a unique fingerprint.

Cite this