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. © 2010 Wiley‐Liss, Inc.

[1]  C. Spencer,et al.  Identification of loci associated with schizophrenia by genome-wide association and follow-up , 2008, Nature Genetics.

[2]  T. Kudo,et al.  TATA Box‐Binding Protein gene is associated with risk for schizophrenia, age at onset and prefrontal function , 2009, Genes, brain, and behavior.

[3]  J. Lieberman,et al.  Recent advances in the development of novel pharmacological agents for the treatment of cognitive impairments in schizophrenia. , 2007, Schizophrenia bulletin.

[4]  Ayman H. Fanous,et al.  Replication of association between schizophrenia and ZNF804A in the Irish Case Control Study of Schizophrenia (ICCSS) sample , 2010, Molecular Psychiatry.

[5]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[6]  I. Gottesman,et al.  The endophenotype concept in psychiatry: etymology and strategic intentions. , 2003, The American journal of psychiatry.

[7]  Cameron S Carter,et al.  Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. , 2005, Schizophrenia bulletin.

[8]  Takahisa Taguchi,et al.  Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. , 2006, Human molecular genetics.

[9]  A. Meyer-Lindenberg,et al.  Intermediate phenotypes and genetic mechanisms of psychiatric disorders , 2006, Nature Reviews Neuroscience.

[10]  R A Ophoff,et al.  Expanding the range of ZNF804A variants conferring risk of psychosis , 2011, Molecular Psychiatry.

[11]  M. Tsuang Schizophrenia: genes and environment , 2000, Biological Psychiatry.

[12]  S Cichon,et al.  Effects of a genome-wide supported psychosis risk variant on neural activation during a theory-of-mind task , 2011, Molecular Psychiatry.

[13]  Tyrone D. Cannon,et al.  Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q. , 2004, Human molecular genetics.

[14]  Daniel R. Weinberger,et al.  Intermediate phenotypes in schizophrenia: a selective review , 2005, Dialogues in clinical neuroscience.

[15]  H. Deng,et al.  Population-based and family-based association studies of ZNF804A locus and schizophrenia , 2011, Molecular Psychiatry.

[16]  D. Weinberger,et al.  Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia , 2007, Molecular Psychiatry.

[17]  Vladimir I. Vladimirov,et al.  Replication of association between schizophrenia and ZNF804A in the Irish Case Control Study of Schizophrenia (ICCSS) sample , 2009, Molecular Psychiatry.

[18]  I. Gottesman,et al.  Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. , 2000, American journal of medical genetics.

[19]  Michael F. Green,et al.  Identification of separable cognitive factors in schizophrenia , 2004, Schizophrenia Research.

[20]  S. Cichon,et al.  Neural Mechanisms of a Genome-Wide Supported Psychosis Variant , 2009, Science.