  The genes that encode the targets of most therapies do not have rare variants
with large-effect or common variants with moderate effects on the biomarker
reflecting the pharmacologic action of the corresponding therapy. Therefore,
providing genetic target validation for most therapies is challenging. Novel
methods are being developed to combine multiple variants in the gene encoding
the target of a therapy that are weakly associated with the biomarker
reflecting the pharmacologic action of that therapy into a genetic score that
can be used as an adequate instrumental variable. We describe one approach to
solve this important problem.
