Investigation of genetic association between human Frizzled homolog 3 gene (FZD3) and schizophrenia: results in a Korean population and evidence from meta-analysis

Psychiatry Res. 2006 Jun 30;143(1):1-11. doi: 10.1016/j.psychres.2005.07.026. Epub 2006 May 16.

Abstract

The neurodevelopmental hypothesis offers a promising approach through which to explore the pathogenesis of schizophrenia. Human Frizzled-3 protein is one of the major components of the Wnt signaling pathway and plays a crucial role in regulating early neurodevelopmental processes. Therefore, the human Frizzled homolog 3 (FZD3) gene, which encodes this protein, may be an excellent candidate gene for association studies of schizophrenia. To replicate the previously reported positive association between FZD3 and schizophrenia in Han Chinese and Japanese populations, we genotyped two single nucleotide polymorphism (SNP) markers of FZD3 in 241 unrelated schizophrenic patients and 192 control subjects. Fisher's exact test was used to compare the genotypic and allelic frequencies in the two groups. In addition, to integrate and evaluate the accumulated evidence published to date, we performed a meta-analysis on the published data, including our own. No evidence was found to support the association between either of the investigated SNP markers and schizophrenia in a Korean population. Moreover, the meta-analytic result did not support the association between several commonly investigated markers in FZD3 and schizophrenia. Failure to replicate previous positive association results could reflect various theoretical factors. Therefore, other sources of error have to be ruled out before coming to a conclusion. In the case of FZD3, it seems that repeated failures to replicate the original results by several independent research groups combine to provide evidence against an association between FZD3 and schizophrenia. Other candidate genes involved in early neurodevelopmental processes may deserve further investigation.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian Continental Ancestry Group*
  • Codon / genetics
  • Frizzled Receptors / genetics*
  • Genotype
  • Humans
  • Korea / epidemiology
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, G-Protein-Coupled / genetics*
  • Schizophrenia / genetics*

Substances

  • Codon
  • FZD3 protein, human
  • Frizzled Receptors
  • Receptors, G-Protein-Coupled