The Impact of a Genome-Wide Supported Psychosis Variant in the ZNF804A Gene on Memory Function in Schizophrenia

A recent genome-wide association study showed that a variant (rs1344706) in the ZNF804A gene was associated with schizophrenia and bipolar disorder. Replication studies supported the evidence for association between this variant in the ZNF804A gene and schizophrenia and that this variant is the most likely susceptibility variant. Subsequent functional magnetic resonance imaging studies in healthy subjects demonstrated the association of the high-risk ZNF804A variant with neural activation during a memory task and a theory of mind task. As these cognitive performances are disturbed in patients with schizophrenia, this gene may play a role in cognitive dysfunction in schizophrenia. The aim of the current study was to investigate the potential relationship between this ZNF804A polymorphism and memory function. The effects of the high-risk ZNF804A genotype, diagnosis, and genotype-diagnosis interaction on verbal memory, visual memory (VisM), attention/concentration, and delayed recall (measured by the Wechsler Memory Scale-Revised) were analyzed by two-way analysis of covariance in 113 patients with schizophrenia and 184 healthy subjects. Consistent with previous studies, patients with schizophrenia exhibited poorer performance on all indices as compared to healthy control subjects (P<0.001). A significant ZNF804A genotype-diagnosis interaction was found for VisM performance (P-0.0012). Patients with the high-risk T/T genotype scored significantly lower on VisM than G carriers did (P-0.018). In contrast, there was no genotype effect for any index in the healthy control subjects (P>0.05). Our data suggest that rs1344706 may be related to memory dysfunction in schizophrenia. (C) 2010 Wiley-Liss, Inc.