BACKGROUND: Genetic and biological evidence supports a role for DISC1 across a spectrum of major mental illnesses, including schizophrenia and bipolar disorder. There is evidence for genetic interplay between variants in DISC1 and in biologically interacting loci in psychiatric illness. DISC1 also associates with normal variance in behavioral and brain imaging phenotypes. METHODOLOGY: Here, we analyze public domain datasets and demonstrate correlations between variants in the DISC1 pathway genes and levels of gene expression. Genetic variants of DISC1, NDE1, PDE4B and PDE4D regulate the expression of cytoskeletal, synaptogenic, neurodevelopmental and sensory perception proteins. Interestingly, these regulated genes include existing targets for drug development in depression and psychosis. CONCLUSIONS: Our systematic analysis provides further evidence for the relevance of the DISC1 pathway to major mental illness, identifies additional potential targets for therapeutic intervention and establishes a general strategy to mine public datasets for insights into disease pathways.
- Cyclic Nucleotide Phosphodiesterases, Type 3/genetics/metabolism Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/metabolism Databases, Factual *Gene Expression Regulation Gene Regulatory Networks Genetic Predisposition to Disease Humans *Mental Disorders/genetics/metabolism Microtubule-Associated Proteins/genetics/metabolism *Nerve Tissue Proteins/genetics/metabolism Perception/*physiology Synapses/*physiology