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Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Voisey, Joanne, Swagell, C.D., Hughes, Ian P., Lawford, Bruce R., Young, Ross McD., & Morris, C.P. (2010) Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia. European Psychiatry, 25(6), pp. 314-319.

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Abstract

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

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ID Code: 40670
Item Type: Journal Article
Additional URLs:
Keywords: Schizophrenia and psychosis, Genetics, Molecular Biology, Polymorphism, Genetic Association, Glutamatergic Pathway, Dystrobrevin Binding Protein 1
DOI: 10.1016/j.eurpsy.2009.11.011
ISSN: 0924-9338
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > PSYCHOLOGY (170100)
Divisions: Past > Schools > Cell & Molecular Biosciences
Current > QUT Faculties and Divisions > Faculty of Health
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Psychology & Counselling
Copyright Owner: Copyright © 2010 Elsevier Masson SAS All rights reserved.
Deposited On: 11 Mar 2011 09:22
Last Modified: 01 Mar 2012 00:16

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