Clinical symptomatology and the psychosis risk gene, ZNF804A

Abstract

The single nucleotide polymorphism (SNP) rs1344706, mapping to the gene ZNF804A, has been implicated in schizophrenia susceptibility ([O'Donovan et al., 2008], [International Schizophrenia Consortium, 2009], [Stefansson et al., 2009] and [Steinberg et al., 2010]). The original study reported stronger association when the phenotype was broadened to include bipolar disorder (p = 9.96 ? 10? 9) (O'Donovan et al. 2008), but the variant is likely to have a modest effect on disease risk (OR = 1.12). Understanding the function of psychosis risk genes is a key step towards understanding disease biology. Little is currently known about the encoding protein, zinc finger protein 804A, except that it is brain-expressed and predicted to be involved in regulation of gene expression. Two recent studies suggest that the ZNF804A risk allele is likely to influence brain function, both with respect to connectivity within and between the dorsolateral prefrontal cortex and hippocampus (Esslinger et al. 2009) and on episodic and working memory (Walters et al., in press Walters J.T.R., Corvin A., Williams H., Dragovic M., Quinn E.M., et al. In Press. The psychosis susceptibility gene ZNF804A is associated with less impaired cognitive performance in schizophrenia. Archives of General psychiatry.Walters et al. in press).