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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

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Association analysis between schizophrenia and the AP-3 complex genes.

Ryota Hashimoto¹, Kazutaka Ohi, Takeya Okada

¹The Osaka-Hamamatsu Joint Research Center for Child Mental Development, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hashimor@psy.med.osaka-u.ac.jp

Neuroscience Research

|June 2, 2009

Summary

Schizophrenia susceptibility gene dysbindin interacts with the adaptor protein (AP)-3 complex. This study found no significant association between AP3 complex genes and schizophrenia risk in the studied population.

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Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Dysbindin, a schizophrenia susceptibility gene, is part of the biogenesis of lysosome-related organelles complex (BLOC)-1.
BLOC-1 interacts with the adaptor protein (AP)-3 complex, suggesting a potential role in schizophrenia pathogenesis.

Purpose of the Study:

To investigate the association between single nucleotide polymorphisms (SNPs) in AP3 complex genes and schizophrenia.
To explore the role of the AP3 complex in the genetic etiology of schizophrenia.

Main Methods:

Genotyping of 16 SNPs within AP3 complex genes.
Case-control study design with 432 schizophrenia cases and 656 healthy controls.
Statistical analysis including chi-squared tests and odds ratio calculation.

Main Results:

A nominal association was observed between rs6688 in the AP3M1 gene and schizophrenia (P=0.012).
This association did not remain significant after correction for multiple testing (corrected P=0.192).
No other significant associations were found between the studied SNPs and schizophrenia.

Conclusions:

The AP3 complex genes may not play a substantial role in the development of schizophrenia in the investigated population.
Further research is needed to fully elucidate the genetic underpinnings of schizophrenia.