A critical issue in the field is how to use genetics information to drive drug discovery. As reviewed above, it often is not clear what genes are driving the association for GWAS significant loci. A potentially paradigmic example has recently emerged. C4 copy number was recently confirmed as a schizophrenia risk locus potentially affecting synaptic pruning in neurodevelopment; this study used PGC2 schizophrenia GWAS data, expression data from 700 postmortem brains, and genetic engineering of mice to confirm a potential mechanism20. This is already encouraging the development of new therapeutics, because synaptic pruning occurs as the brain develops to full maturity in the late teens/early adulthood, providing time during which therapeutic interventions may be possible.
