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Mendelian randomization for studying the effects of perturbing drug targets
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 i...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
F1000 Research Limited
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903200/ https://www.ncbi.nlm.nih.gov/pubmed/33644404 http://dx.doi.org/10.12688/wellcomeopenres.16544.2 |
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author | Gill, Dipender Georgakis, Marios K. Walker, Venexia M. Schmidt, A. Floriaan Gkatzionis, Apostolos Freitag, Daniel F. Finan, Chris Hingorani, Aroon D. Howson, Joanna M.M. Burgess, Stephen Swerdlow, Daniel I. Davey Smith, George Holmes, Michael V. Dichgans, Martin Scott, Robert A Zheng, Jie Psaty, Bruce M. Davies, Neil M. |
author_facet | Gill, Dipender Georgakis, Marios K. Walker, Venexia M. Schmidt, A. Floriaan Gkatzionis, Apostolos Freitag, Daniel F. Finan, Chris Hingorani, Aroon D. Howson, Joanna M.M. Burgess, Stephen Swerdlow, Daniel I. Davey Smith, George Holmes, Michael V. Dichgans, Martin Scott, Robert A Zheng, Jie Psaty, Bruce M. Davies, Neil M. |
author_sort | Gill, Dipender |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7903200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | F1000 Research Limited |
record_format | MEDLINE/PubMed |
spelling | pubmed-79032002021-02-25 Mendelian randomization for studying the effects of perturbing drug targets Gill, Dipender Georgakis, Marios K. Walker, Venexia M. Schmidt, A. Floriaan Gkatzionis, Apostolos Freitag, Daniel F. Finan, Chris Hingorani, Aroon D. Howson, Joanna M.M. Burgess, Stephen Swerdlow, Daniel I. Davey Smith, George Holmes, Michael V. Dichgans, Martin Scott, Robert A Zheng, Jie Psaty, Bruce M. Davies, Neil M. Wellcome Open Res Review 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. F1000 Research Limited 2021-02-10 /pmc/articles/PMC7903200/ /pubmed/33644404 http://dx.doi.org/10.12688/wellcomeopenres.16544.2 Text en Copyright: © 2021 Gill D et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Gill, Dipender Georgakis, Marios K. Walker, Venexia M. Schmidt, A. Floriaan Gkatzionis, Apostolos Freitag, Daniel F. Finan, Chris Hingorani, Aroon D. Howson, Joanna M.M. Burgess, Stephen Swerdlow, Daniel I. Davey Smith, George Holmes, Michael V. Dichgans, Martin Scott, Robert A Zheng, Jie Psaty, Bruce M. Davies, Neil M. Mendelian randomization for studying the effects of perturbing drug targets |
title | Mendelian randomization for studying the effects of perturbing drug targets |
title_full | Mendelian randomization for studying the effects of perturbing drug targets |
title_fullStr | Mendelian randomization for studying the effects of perturbing drug targets |
title_full_unstemmed | Mendelian randomization for studying the effects of perturbing drug targets |
title_short | Mendelian randomization for studying the effects of perturbing drug targets |
title_sort | mendelian randomization for studying the effects of perturbing drug targets |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903200/ https://www.ncbi.nlm.nih.gov/pubmed/33644404 http://dx.doi.org/10.12688/wellcomeopenres.16544.2 |
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