Gill, D;
Georgakis, MK;
Walker, VM;
Schmidt, AF;
Gkatzionis, A;
Freitag, DF;
Finan, C;
... Davies, NM; + view all
(2021)
Mendelian randomization for studying the effects of perturbing drug targets [version 1; peer review: awaiting peer review].
Wellcome Open Research
, 6
, Article 16. 10.12688/WELLCOMEOPENRES.16544.1.
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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.
| Type: | Article |
|---|---|
| Title: | Mendelian randomization for studying the effects of perturbing drug targets [version 1; peer review: awaiting peer review] |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.12688/WELLCOMEOPENRES.16544.1 |
| Publisher version: | https://doi.org/10.12688/wellcomeopenres.16544.1 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Drugs, Genetics, Mendelian randomization |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10137807 |
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