Common pitfalls in drug target Mendelian randomization and how to avoid them
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
Drug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which it can be performed even before commencing clinical studies.
Main body
In this review, we describe the recent emergence of drug target Mendelian randomization, its common pitfalls, how best to address them, as well as potential future directions. Throughout, we offer advice based on our experiences on how to approach these types of studies, which we hope will be useful for both practitioners and those translating the findings from such work.
Conclusions
Drug target Mendelian randomization is nuanced and requires a combination of biological, statistical, genetic, epidemiological, clinical, and pharmaceutical expertise to be utilized to its full potential. Unfortunately, these skillsets are relatively infrequently combined in any given study.
Drug target Mendelian randomization describes the use of genetic variants as instrumental variables for studying the effects of pharmacological agents. The paradigm can be used to inform on all aspects of drug development and has become increasingly popular over the last decade, particularly given the time- and cost-efficiency with which it can be performed even before commencing clinical studies.
Main body
In this review, we describe the recent emergence of drug target Mendelian randomization, its common pitfalls, how best to address them, as well as potential future directions. Throughout, we offer advice based on our experiences on how to approach these types of studies, which we hope will be useful for both practitioners and those translating the findings from such work.
Conclusions
Drug target Mendelian randomization is nuanced and requires a combination of biological, statistical, genetic, epidemiological, clinical, and pharmaceutical expertise to be utilized to its full potential. Unfortunately, these skillsets are relatively infrequently combined in any given study.
Date Issued
2024-10-15
Date Acceptance
2024-10-10
Citation
BMC Medicine, 2024, 22
ISSN
1741-7015
Publisher
BMC
Journal / Book Title
BMC Medicine
Volume
22
Copyright Statement
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the
original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or
other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this
licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-024-03700-9
Publication Status
Published
Article Number
473
Date Publish Online
2024-10-15