Association study of the human FZD3 locus with schizophrenia

Background: The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins involved in the Wnt signal transduction cascades. The alteration of Wnt signal transduction cascades has been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene is mapped to chromosome 8p21, which is a potential region containing a gene for schizophrenia, it may play a role in conferring susceptibility to the disease. Methods: This study was conducted with the detection of three single nucleotide polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis among 246 schizophrenic family trios of Chinese Han descent. Results: The transmission disequilibrium test (TDT) demonstrated that the three SNPs all showed a preferential transmission with a p value ranging from .0003-.000007. The global chi-squared test for haplotype transmission also showed a strong association (chi(2) = 48.84, df = 7, p < .000001). Conclusions: The strong association between the FZD3 locus and schizophrenia suggests that the gene itself may play a role in underlying schizophrenia, although a nearby gene responsible for predisposing to the illness cannot be ruled out.