Insight into which genes (and which gene-products) are implicated and the direction of effect is needed to determine the most appropriate therapeutic strategy. A general understanding of the additional steps in the target identification and qualification process has developed: GWAS locus-to-gene mapping to determine which gene(s) give rise to the association, plus functional studies of how the disease-associated SNPs operate (modality), either via regulatory effects (e.g. affecting RNA splicing or levels) or through direct functional effects (affecting the nature and function of a protein). In this way, therapeutics targeting single GWAS identified targets, such as HMGCR in the LDL cholesterol metabolism responsible for hypercholesterolemia19, have been successfully developed. This process is beginning for schizophrenia20, and the PGC aims to accelerate this for all psychiatric disorders.
