To fully exploit GWAS data for drug development, we need to complement the direct identification of single targets and their interactors and the use of polygenic risk scores with pathway-driven approaches, explicitly targeting sets of GWAS implicated regions/proteins together. In our view, this may be a powerful means to discover new drug indications/targets that gains power by exploiting the underlying polygenic nature of these disorders. This mirrors the observation that many successful psychiatric (and other) drugs have complex receptor pharmacology profiles binding multiple targets with different affinities. The PGC is planning to exploit pathway analysis methods38 that show better control for type 1 error alongside chemoinformatically generated gene sets to identify drugs or molecules with sets of targets significantly enriched for association in GWAS data. Applying drug pathway analyses to psychiatric GWAS results will allow us to derive hypotheses about drug mechanisms of action and rational drug repurposing39. Rare variants, discovered by large scale sequencing efforts, can also be included in these analyses, particularly the known recurrent Copy Number Variations in Autism and Schizophrenia40. These are complemented by ongoing large
