Morris, D. W., Murphy, K., Kenny, N., Purcell, S. M., McGhee, K. A., Schwaiger, S., Nangle, J.-M., Donohoe, G., Clarke, S., Scully, P., Quinn, J., Meagher, D., Baldwin, P., Crumlish, N., O'Callaghan, E., Waddington, J. L., Gill, M. and Corvin, A. P., 2008. Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): main and epistatic gene effects are potential contributors to schizophrenia susceptibility. Biological psychiatry, 63 (1), pp. 24-31.
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BACKGROUND: The DTNBP1 gene, encoding dysbindin, has been strongly implicated in schizophrenia (SZ) susceptibility by a series of independent genetic association and gene expression studies. Among its known functions, dysbindin is part of a protein complex, termed the biogenesis of lysosome-related organelles complex 1 (BLOC-1), the molecular components of which might be involved in the regulation of vesicular trafficking and dendrite branching. METHODS: A systematic investigation of the other seven BLOC-1 genes (MUTED, PLDN, CNO, SNAPAP, BLOC1S1, BLOC1S2, and BLOC1S3) for evidence of association with SZ was undertaken in a sample of 373 SZ cases and 812 control subjects. Possible epistasis between combinations of BLOC-1 genes, including DTNBP1, was tested with a novel method of investigating for gene-gene interaction. Quality control measures were incorporated into genotyping strategy, and all results were corrected for multiple testing to prevent false positive results. RESULTS: We identified significant evidence of association between BLOC1S3 and SZ (odds ratio = 1.45, confidence interval = 1.13-1.86, p = .0028, corrected p = .0389). We also report evidence for epistatic interaction between DTNBP1 and MUTED contributing to SZ in the absence of a significant main effect at MUTED (p = .0009, corrected p = .0252). Single marker and epistasis results remained significant after correction for multiple testing. CONCLUSIONS: Together these data provide evidence for the involvement of the BLOC-1 protein complex in SZ pathogenesis.
|Uncontrolled Keywords:||BLOC-1; dysbindin; epistasis; gene; muted; schizophrenia|
|Subjects:||Technology > Medicine and Health|
|Group:||School of Health and Social Care|
|Deposited By:||Dr Kevin McGhee|
|Deposited On:||05 May 2010 19:56|
|Last Modified:||07 Mar 2013 15:27|
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