Gene polymorphisms of DISC1 is associated with schizophrenia: Evidence from a meta-analysis

DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

“…As mentioned above, there are candidate functional variants of DISC1, although the identity of the functional DISC1 variant(s) that may be predisposing to psychiatric disease continues to be unknown. The effects of disrupting DISC1 appeared in an originally Scottish family seem to arise as a results of haplo insufficiency rather than the loss of function, since none of the members of the family were reported to be homozygous for the translocation, a possible dominant negative mechanism cannot be dominated out . It is possible that the predisposing haplotypes identified in block 1 are also related to lower levels of transcription as a results of changes in putative intronic enhancer parts .…”

“…rs6675281 (exon 9) leads to a nonsynonymous modification in residue 607 within the DISC1 binding site for FEZ1; instead introns 9 to 10 SNPs may affect DISC1 splicing. The short isoform is spliced from exon 9 to an alternate exon 9, between exons 9 and 10 . Thus, SNPs in DNA 9 could affect short isoform expression .…”

“…It is possible that the predisposing haplotypes identified in block 1 are also related to lower levels of transcription as a results of changes in putative intronic enhancer parts . An alternative is that the associating haplotypes may carry currently unknown missense or nonsense mutations within the coding sequence . The converging information from multiple studies recommend that schizophrenia has an overlapping root in altered DISC1 function or expression, however it is possible that different variants within the DISC1 gene determine variations in phenotype through corresponding variation in interactions with DISC1’s‐binding partners .…”

“…Consistent with its potential influence on hippocampal structure and performance, DISC1 expression is prominent in the limbic structure . The distribution of DISC1 protein between cell varieties and compartments has not been adequately defined, but is said to be localized in mitochondria as well as in cytoplasm, nuclei, neurites, and subsequently the plasma membrane…”

Disrupted‐in‐schizophrenia 1 functional polymorphisms and D2/D3 receptor availability: A [11C]‐(+)‐PHNO imaging study

“…Ser704Cys, Leu607Ph and Arg264Gln have all been shown to have biological impacts on cellular signalling transduction pathways such as extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) and Wnt signalling . All three polymorphisms have also been associated with an increased risk for psychosis and also with the severity of positive psychotic symptoms in some studies . However, it should be acknowledged that the involvement of the DISC1 gene in schizophrenia is debated and that these DISC1 polymorphisms have not been linked to schizophrenia or any other psychiatric disorders in Psychiatric Genomics Consortium genome‐wide association studies.…”