Phenotypes associated with genes encoding drug targets are predictive of clinical trial side effects. View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Phuong A Nguyen, David A Born, Aimee M Deaton, Paul Nioi, Lucas D Ward

ABSTRACT

Only a small fraction of early drug programs progress to the market, due to safety and efficacy failures, despite extensive efforts to predict safety. Characterizing the effect of natural variation in the genes encoding drug targets should present a powerful approach to predict side effects arising from drugging particular proteins. In this retrospective analysis, we report a correlation between the organ systems affected by genetic variation in drug targets and the organ systems in which side effects are observed. Across 1819 drugs and 21 phenotype categories analyzed, drug side effects are more likely to occur in organ systems where there is genetic evidence of a link between the drug target and a phenotype involving that organ system, compared to when there is no such genetic evidence (30.0 vs 19.2%; OR = 1.80). This result suggests that human genetic data should be used to predict safety issues associated with drug targets. More... »

PAGES

1579

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09407-3

    DOI

    http://dx.doi.org/10.1038/s41467-019-09407-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113261503

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30952858


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