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Mendelian randomization for studying the effects of perturbing drug targets
- Source :
- Wellcome Open Research, Gill, D, Georgakis, M K, Walker, V M, Schmidt, A F, Gkatzionis, A, Freitag, D F, Finan, C, Hingorani, A D, Howson, J M M, Burgess, S, Swerdlow, D I, Davey Smith, G, Psaty, B M & Davies, N M 2021, ' Mendelian randomization for studying the effects of perturbing drug targets ', Wellcome Open Research, vol. 6, 16 . https://doi.org/10.12688/wellcomeopenres.16544.2
- Publication Year :
- 2021
-
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.
- Subjects :
- 0301 basic medicine
Drug
Computer science
media_common.quotation_subject
Medicine (miscellaneous)
Review
Computational biology
030204 cardiovascular system & hematology
ENCODE
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Empirical research
Mendelian randomization
Genetics
Genetic association
media_common
Mechanism (biology)
Confounding
Drugs
Articles
3. Good health
030104 developmental biology
Drug development
Subjects
Details
- ISSN :
- 2398502X
- Database :
- OpenAIRE
- Journal :
- Wellcome Open Research
- Accession number :
- edsair.doi.dedup.....6800d380ef162c233049a5551cdc4800
- Full Text :
- https://doi.org/10.12688/wellcomeopenres.16544.2