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
Key Words
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Article info
Publication history
Published online: July 09, 2007
Accepted:
December 26,
2006
Received in revised form:
October 20,
2006
Received:
August 17,
2006
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
