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Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): main and epistatic gene effects are potential contributors to schizophrenia susceptibility.

Abstract：

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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Morris DW,Murphy K,Kenny N,Purcell SM,McGhee KA,Schwaiger S,Nangle JM,Donohoe G,Clarke S,Scully P,Quinn J,Meagher D,Baldwin P,Crumlish N,O'Callaghan E,Waddington JL,Gill M,Corvin AP

doi

10.1016/j.biopsych.2006.12.025

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

24-31

issue

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(07)00006-6

journal_volume

pub_type

杂志文章

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Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): main and epistatic gene effects are potential contributors to schizophrenia susceptibility.