| 1 | Biol. Psychiatry 2008 Jan 63: 13-6 |
|---|---|
| PMID | 17553464 |
| Title | Positional pathway screen of wnt signaling genes in schizophrenia: association with DKK4. |
| Abstract | Wnt signaling has been implicated in schizophrenia from studies of gene expression in patients, from an understanding of the function of reported susceptibility genes and from experimental studies of psychoactive drugs. This diverse evidence suggests that wnt signaling genes, defined as pathway participants, modifiers or targets, are good candidates as susceptibility factors. We performed a combined positional and candidate association screen by identifying known wnt signaling genes in regions linked to schizophrenia. In a staged study we examined over 50 single nucleotide polymorphisms (SNPs) in 28 wnt signaling genes, first in trios of Chinese origin and then in a case-control series from Hong Kong. In both sets, Dickkopf 4 (DKK4) was associated with schizophrenia - with an odds ratio of 3.9 (p < .01, CI = 1.3-11.1) in the combined sample. As DKK family members have previously been found to show altered expression in schizophrenia brain and to bind to neuregulin, this finding suggests that DKK4 may play a role in schizophrenia pathogenesis. |
| SCZ Keywords | schizophrenia |
| 2 | Mol. Psychiatry 2009 Jun 14: 563-89 |
| PMID | 19204725 |
| Title | Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. |
| Abstract | Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence. |
| SCZ Keywords | schizophrenia |
| 3 | Zool. Res. 2011 Feb 32: 62-5 |
| PMID | 21341386 |
| Title | [Association of the schizophrenia susceptible gene DKK4 with brain volume in Chinese populations]. |
| Abstract | schizophrenia is one of the most severe mental disorders with a worldwide incidence of 1%. Previous studies suggested that the brain volumes of the schizophrenia patients were much smaller than the healthy individuals and many schizophrenia susceptible genetic variants have been shown associated with structural brain abnormalities in patients, which is consistent with the neurodevelopmental hypothesis of the etiology of schizophrenia. Recently, the DKK4 gene involved in the Wnt signaling was found to be significantly associated with schizophrenia. To test whether DKK4 is associated with neurodevelopment, we genotyped one DKK4 SNP in 961 healthy Chinese individuals and measured their brain volumes. We found that the SNP was significantly associated with brain volume under both additive and dominant genetic models, providing evidence that schizophrenia susceptible genes could influence brain volume. Our findings support the neurodevelopmental hypothesis of the etiology of schizophrenia. |
| SCZ Keywords | schizophrenia |