Plenge Lab
Date posted: June 7, 2018 | Author: | No Comments »

Categories: Drug Discovery Human Genetics

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

I recently participated in a Harvard Medical School Executive Education course on human genetics and drug discovery (link here, slides here and here). My presentation concluded with a short discussion on emerging resources such as Phenome-Wide Association Studies (PheWAS) to predict adverse drug events and guide indication selection, and protein quantitative trait loci (pQTLs) for Mendelian randomization. In this blog, I highlight briefly our recent Nature publication on pQTLs, “Genomic atlas of the human plasma proteome” (here), which represents a new public resource for drug discovery.

Human genetic targets are endowed with favorable properties, one of which is the ability to use genetic tools for nature’s randomized control trial. Central to this concept is Mendelian randomization, a method that uses human genetic variants as an instrument to examine the causal effect of a modifiable exposure (e.g., protein biomarker) on disease in observational studies (reviewed here and recent Nature Reviews Genetics here).

Proteins provide an ideal paradigm for Mendelian randomization analysis for drug discovery, as proteins are under proximal genetic control and represent the targets of most approved drugs.

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