The disruption of the disrupted-in-schizophrenia (DISC1) gene segregates with major mental illnesses in a Scottish family. Association of DISC1 with schizophrenia has been reported in several ethnic groups, and now recently with mood disorder.
A family-based association study of DISC1 and bipolar disorder (BP) in 57 bipolar pedigrees was conducted. Then, we examined possible association of bipolar disorder with DISC1 mRNA expression in human lymphoblasts. We also studied the correlation of several clinical features with the levels of DISC1 mRNA expression.
Haplotype analysis identified one haplotype (HP1) that was overtransmitted to the BP phenotype (p = .01) and a second haplotype that was undertransmitted (HP2). There was a gender influence in the transmission distortion, with overtransmission of HP1 to affected females (p = .004). A significant decrease in DISC1 mRNA expression was observed in lymphoblasts from affected HP1 group compared to those from unaffected subjects with the HP2 (p = .006). Further, a higher number of manic symptoms correlated with lower levels of DISC1 expression (p = .008).
These results suggest that decreased mRNA levels of DISC1 expression, associating with the risk haplotype, may be implicated in the pathophysiology of bipolar disorder.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Biological Psychiatry
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
Akiyoshi T, Nakamura M, Koga K, Nakashima H, Yao T, Tsuneyoshi M, et al (in press): Gli1, down-regulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation. Gut.
- Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development.Neuroscience. 2004; 124: 3-10
- DISC1 (Disrupted in Schizophrenia-1) is expressed in limbic regions of the primate brain.Neuroreport. 2003; 14: 951-954
- Are schizophrenic and bipolar disorders related?.Biol Psychiatry. 2000; 48: 531-538
- Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia.Biol Psychiatry. 2000; 47: 245-251
- Schizophrenia and affective disorders–cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: clinical and P300 findings in a family.Am J Hum Genet. 2001; 69: 428-433
- Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders.Mol Cell Neurosci. 2004; 25: 42-55
- Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia.Proc Natl Acad Sci U S A. 2005; 102: 8627-8632
- Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory.Arch Gen Psychiatry. 2005; 62: 1205-1213
- Natural variation in human gene expression assessed in lymphoblastoid cells.Nat Genet. 2003; 33: 422-425
- Finding the intracellular signaling pathways affected by mood disorder treatments.Neuron. 2003; 38: 157-160
- Genome scan of pedigrees multiply affected with bipolar disorder provides further support for the presence of a susceptibility locus on chromosome 12q23-q24, and suggests the presence of additional loci on 1p and 1q.Psychiatr Genet. 2003; 13: 77-84
- Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System.Mutat Res. 2005; 573: 111-135
- A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2.Proc Natl Acad Sci U S A. 1999; 96: 5604-5609
- Replication of 1q42 linkage in Finnish schizophrenia pedigrees.Mol Psychiatry. 2004; 9: 1037-1041
- Chromosome 1 loci in Finnish schizophrenia families.Hum Mol Genet. 2001; 10: 1611-1617
- The structure of haplotype blocks in the human genome.Science. 2002; 296: 2225-2229
- Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13.Arch Gen Psychiatry. 2005; 62: 1081-1088
- Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects.Hum Mol Genet. 2003; 12: 3151-3159
- Disrupted in Schizophrenia 1 (DISC1): Association with Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder.Am J Hum Genet. 2004; 75: 862-872
- The family based association test method: strategies for studying general genotype–phenotype associations.Eur J Hum Genet. 2001; 9: 301-306
- Linkage of schizophrenia with chromosome 1q loci in Taiwanese families.Mol Psychiatry. 2003; 8: 445-452
- A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development.Nat Cell Biol. 2005; 7: 1067-1078
- A genome scan and follow-up study identify a bipolar disorder susceptibility locus on chromosome 1q42.Mol Psychiatry. 2004; 9: 1083-1090
- Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12.Mol Psychiatry. 2003; 8: 288-298
- DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling.Science. 2005; 310: 1187-1191
- Disruption of two novel genes by a translocation co-segregating with schizophrenia.Hum Mol Genet. 2000; 9: 1415-1423
- Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth.Mol Psychiatry. 2003; 8: 685-694
- Genetic analysis of genome-wide variation in human gene expression.Nature. 2004; 430: 743-747
- DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation.Hum Mol Genet. 2003; 12: 1591-1608
- Autophagosome-like vacuole formation in Huntington’s disease lymphoblasts.Neuroreport. 2004; 15: 1325-1328
- Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.Proc Natl Acad Sci U S A. 2003; 100: 289-294
- Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington’s disease patient lymphoblasts.Neurobiol Dis. 2005; 20: 267-274
- Aberrant expression of bcl-2 gene family in Down’s syndrome brains.Brain Res Mol Brain Res. 1997; 48: 53-59
- Genetics.Science. 2005; 310: 1128-1129
- Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization.Nat Med. 1999; 5: 1194-1198
- A form of DISC1 enriched in nucleus: altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse.Proc Natl Acad Sci U S A. 2005; 102: 1187-1192
- Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment.Mol Psychiatry. 2004; 9: 1100-1110
- Association between the TRAX/DISC locus and both bipolar disorder and schizophrenia in the Scottish population.Mol Psychiatry. 2005; 10 (616): 657-668
- Genetic association between schizophrenia and the DISC1 gene in the Scottish population.Am J Med Genet B Neuropsychiatr Genet. 2006; 141: 155-159
Published online: June 29, 2006
Accepted: March 23, 2006
Received in revised form: July 28, 2005
Received: January 26, 2005
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.