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Human Genomics and Drug Development.

Amand F Schmidt1,2,3, Aroon D Hingorani1,2,4, Chris Finan1,2,3,4

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Genomics and Mendelian randomization (MR) accelerate drug discovery by identifying targets, validating them, and optimizing clinical trials. This approach enhances drug development success rates and drug repurposing.

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Area of Science:

  • Genetics
  • Pharmacology
  • Biostatistics

Background:

  • High failure rates in drug development pose significant challenges.
  • Genomics offers insights into human disease, aiding pharmaceutical research.
  • Mendelian randomization (MR) is a robust analytical method for causal inference.

Purpose of the Study:

  • To review the application of genomics in pharmaceutical R&D.
  • To explore the relationship between genomics and Mendelian randomization (MR).
  • To demonstrate how human genomic data can enhance drug development processes.

Main Methods:

  • Utilizing human genomic data linked to pharmaceutically relevant phenotypes.
  • Applying MR for drug target validation (drug target MR).
  • Analyzing statistical and biological considerations for MR application.

Main Results:

  • Genomics facilitates drug target identification and validation.
  • Genomic data aids in evaluating compound-target engagement specificity.
  • Genomics supports selection of clinical trial endpoints and identifies repurposing opportunities.

Conclusions:

  • Genomics-assisted approaches, coupled with MR, offer powerful tools to de-risk drug development.
  • These methods improve target identification, validation, and clinical trial design.
  • Overcoming obstacles is key for scaled application of genomics in drug discovery.