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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.

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