Identifying drug targets for schizophrenia through gene prioritization.

Background

Schizophrenia genome-wide association studies (GWASes) have identified >250 significant loci and prioritized >100 disease-related genes. However, gene prioritization efforts have mostly been restricted to locus-based methods that ignore information from the rest of the genome.

Methods

To more accurately characterize genes involved in schizophrenia etiology, we applied a combination of highly-predictive tools to a published GWAS of 67,390 schizophrenia cases and 94,015 controls. We combined both locus-based methods (fine-mapped coding variants, distance to GWAS signals) and genome-wide methods (PoPS, MAGMA, ultra-rare coding variant burden tests). To validate our findings, we compared them with previous prioritization efforts, known neurodevelopmental genes, and results from the PsyOPS tool.

Results

We prioritized 62 schizophrenia genes, 41 of which were also highlighted by our validation methods. In addition to

Conclusions

We curated a high-quality list of 62 genes that likely play a role in the development of schizophrenia. Developing or repurposing drugs that target these genes may lead to a new generation of schizophrenia therapies. Rodent models of addiction more closely resemble the human disorder than rodent models of schizophrenia. As such, genes prioritized for both disorders could be explored in rodent addiction models, potentially facilitating drug development.