Drug Discovery and the Genetic and Biological Underpinnings of Schizophrenia

Genome-wide association and the analysis of rare genetic variants has provided great insights into the genetic basis of schizophrenia, with over 250 variants now identified. Evidence suggests that genetic evidence for association between a gene and disease (even for low risk, common variants) increased the probability of success as a drug target by two-fold or more (Minikel et al., 2024). However, there are several barriers to drug development using this information, including variant-to-gene mapping, target prioritisation, the validity of disease models, target tractability and the development of a therapeutic hypothesis. On the plus side, mapping of the genes within these loci have identified the dopamine D2 receptor (DRD2) gene, a major target of typical antipsychotic drugs, as well as a number of other genes that produce druggable or potentially druggable proteins (Kraft et al., 2024). In this presentation, potential pathways to drug development and stratification using genetics and genomics will be explored.