Schizophrenia is a complex disorder caused by many genes. Using new gene discoveries to understand pathobiology is a foundation for development of new treatments. The FOXP1 gene encodes an important transcription factor that regulates neocortical organization and circuitry by controlling the expression of other genes. Large-scale genomic studies have established that FOXP1 is associated with increased risk of schizophrenia. Rare mutations in the gene disrupt neurodevelopment cause autism spectrum disorder and intellectual disability. My hypothesis is that FOXP1-regulated genes are influencing different domains of the schizophrenia phenotype? My aim is to identify sets of FOXP1-regulated genes and then use genetic risk scores to determine if FOXP1-regulated genes can predict scores for positive symptoms, negative symptoms and cognitive function in schizophrenia patients. My objectives are to: (i) Perform RNA-seq analysis of gene expression data from FOXP1 knock-out animal models to identify differentially expressed genes. (ii) Use a method called polygenic risk score profiling and linear regression to quantify the contribution that these FOXP1-regulated genes are making to measures of positive symptoms, negative symptoms and cognitive function in an Irish schizophrenia patient sample. It will be interesting to establish if FOXP1-regulated genes are specifically influencing different domains of the schizophrenia phenotype. This would be potentially useful knowledge as it means that biological processes controlled by FOXP1 could become targets for new drug development.
