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Target Discovery for Drug Development Using Mendelian Randomization

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Pharmacogenomics in Drug Discovery and Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2547))

Abstract

Making drug development more efficient by identifying promising drug targets can contribute to resource savings. Identifying promising drug targets using human genetic approaches can remove barriers related to translation. In addition, genetic information can be used to identify potentially causal relationships between a drug target and disease. Mendelian randomization (MR) is a class of approaches used to identify causal associations between pairs of genetically predicted traits using data from human genetic studies. MR can be used to prioritize candidate drug targets by predicting disease outcomes and adverse events that could result from the manipulation of a drug target. The theory behind MR is reviewed, including a discussion of MR assumptions, different MR analytical methods, tests for violations of assumptions, and MR methods that can be robust to some violations of MR assumptions. A protocol to perform two-sample MR (2SMR) with summary genome-wide association study (GWAS) results is described. An example of 2SMR examining the causal relationship between low-density lipoprotein (LDL) and coronary artery disease (CAD) is provided as an illustration of the protocol.

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Acknowledgments

This work was supported by NIH U24AG051129.

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Authors and Affiliations

  1. California Pacific Medical Center Research Institute, San Francisco, CA, USA

    Daniel S. Evans

  2. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA

    Daniel S. Evans

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  1. Daniel S. Evans
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Correspondence to Daniel S. Evans .

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Editors and Affiliations

  1. PharmTao, Santa Clara, CA, USA

    Qing Yan

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© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Evans, D.S. (2022). Target Discovery for Drug Development Using Mendelian Randomization. In: Yan, Q. (eds) Pharmacogenomics in Drug Discovery and Development. Methods in Molecular Biology, vol 2547. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2573-6_1

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  • DOI: https://doi.org/10.1007/978-1-0716-2573-6_1

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2572-9

  • Online ISBN: 978-1-0716-2573-6

  • eBook Packages: Springer Protocols

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