Together, our results show that Zswim6 is indispensable to normal brain function and support the notion that Zswim6 might serve as an important contributor to the pathogenesis of schizophrenia and other neurodevelopmental disorders.
Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62×10(-5) and P = 9.00×10(-5), respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function.
After comparing with the differentially expressed genes in SCZ brain tissues, 49 overlapped genes were identified for meQTLs, such as ZSCAN12, BTN3A2 and HLA-DQA1.
Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture.
Here, we review literature recently published on ZNF804A, and analyze critical concepts related to the biology of ZNF804A and the role of rs1344706 in schizophrenia and bipolar disorder.
The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.
In contrast, rs1344706 genotype had a significant effect on ZNF804A allelic expression in second-trimester fetal brain, with the schizophrenia risk (T) allele associated with reduced ZNF804A expression.
For example, variation at ZNF804A is associated with risk of both bipolar disorder and schizophrenia, and some rare CNVs are associated with risk of autism and epilepsy as well as schizophrenia.
These include ZNF804A, TCF4 and NRGN, which contain common variants that weakly increase schizophrenia susceptibility, and NRXN1, in which rare copy number variants have a greater impact on schizophrenia risk.
However, the authors identified two ZNF804A promoter SNPs that were significantly associated with schizophrenia in both samples, and the significance was strengthened in the combined samples and further supported by haplotype analysis.
Association analysis of ZNF804A (zinc finger protein 804A) rs1344706 with therapeutic response to atypical antipsychotics in first-episode Chinese patients with schizophrenia.
No difference was observed between the patients with schizophrenia and controls from the Australian Tissue Resource Center samples in the mRNA levels of ZNF804A, OPCML, RPGRIP1L, NRGN, or TCF4.
Our findings suggest that ZNF804A risk variant influence WM integrity involving cortico-limbic brain regions in SCZ and highlight the importance of investigating the impact of genome-wide supported risk factors on intermediate phenotypes with potential to shed light on the neurobiology of SCZ.
The ZNF804A and CACNA1C loci appear to influence risk for both disorders, a finding that supports the hypothesis that schizophrenia and BD are not aetiologically distinct.
In this 2-stage study, we tested for an association between ZNF804Ars1344706 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attention) in an Irish discovery sample.
These findings suggest that ZNF804A affects the GMV of the prefrontal cortex by interacting with COMT, which may improve our understanding of neurobiological effect of ZNF804A and its association with schizophrenia.
We showed that ATXN1 was the only direct PPI partner of the know SCZ risk gene ZNF804A, and it also had direct PPIs with other 18 known SCZ risk genes.
Impairments in hippocampus-PFC functional connectivity are implicated in schizophrenia and are associated with a polymorphism within the ZNF804A gene that shows a genome-wide significant association with schizophrenia.
Previous studies indicated that the single nucleotide polymorphism (SNP) rs1344706 in the gene ZNF804A encoding zinc finger protein 804A was associated with schizophrenia in Caucasian population but not in Chinese Han population.
ZNF804A, encoding the transcription factor zinc-finger protein 804A, is a genome-wide supported psychosis gene associated with schizophrenia and bipolar disorder.