Knockdown of the psychosis susceptibility gene ZNF804A alters expression of genes involved in cell adhesion.

Genome-wide association studies have convincingly implicated several novel genes in susceptibility to schizophrenia and bipolar disorder. The first genome-wide significant association with the broad phenotype of psychosis was with a polymorphism in the ZNF804A gene. However, the biological function(s) of ZNF804A have, to date, been entirely unknown. In this study, we manipulated the expression of ZNF804A in neural progenitor cells derived from human cortical neuroepithelium and assessed its effects on the cellular transcriptome. Gene ontology analysis of differentially expressed genes indicated a significant effect of ZNF804A knockdown on the expression of genes involved in cell adhesion, suggesting a role for ZNF804A in processes such as neural migration, neurite outgrowth and synapse formation. Several highly significant gene expression changes were confirmed in repeat cell culture experiments. Most consistent gene expression changes were seen for C2ORF80, a gene of as-yet-unknown function, and STMN3, a gene involved in neurite outgrowth and axonal and dendritic branching. These data, generated in a hypothesis-free manner, provide a basis for more targeted investigations of ZNF804A function.