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Adverse drug event (ADE) phenome-wide association study (PheWAS) with ACLY gene

05:57 EDT 26 Mar 2019 | Plenge-Gen

[Disclaimer: I am an employee of Celgene. The views expressed here are my own.]

Human genetics offers the potential to identify drug targets and to inform decision-making on the journey to an approved drug. A recent study by Ference et al in the New England Journal of Medicine (NEJM) provides an example of human genetics in action. While most of the study focuses on Mendelian randomization to establish a relation among ACLY genetic variation, LDL cholesterol levels, and cardiovascular events, in this blog I focus on a topic highlighted in the companion NEJM editorial: human genetics to predict on-target adverse drug events (see NEJM editorial here).

First, what is the framework for the application of human genetics to predict on-target adverse drug events (ADEs)?  Briefly, human genetics can predict on-target toxicity if the following criteria are met: (1) unambiguous association of genetic variant to a clinical phenotype that is a surrogate for drug efficacy and toxicity; (2) unambiguous relationship between disease-associated variant and implicated gene that is the target of the therapeutic intervention; (3) quantitative assessment of gene function and clinical phenotypes of efficacy and toxicity to estimate a “genotype-phenotype dose-response” relationship; and (4) confidence that the therapeutic intervention mimics the mechanism of action of the disease-associated variant.…

The post Adverse drug event (ADE) phenome-wide association study (PheWAS) with ACLY gene appeared first on Plenge Gen @rplenge.

Original Article: Adverse drug event (ADE) phenome-wide association study (PheWAS) with ACLY gene

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