Transmission/disequilibrium Test Of Candidate Genes For Schizophrenia

Numerous family, twin, and adoption studies have demonstrated the role of genetic components in the aetiology of schizophrenia. However, major common risk loci have not been found. In this work, I, together with colleagues, have compared the properties of the Transmission/disequilibrium test (TDT) with linkage and association approaches in any details, from which we propose that TDT analysis using candidate gene strategy is a powerful method in identification of susceptibility alleles for complex diseases such as schizophrenia.COMT and N0TCH4 gene have been suggested as a promising candidate for the vulnerability to schizophrenia in view of both its function and location in the genome. To further investigate their roles in schizophrenia susceptibility, several polymorphic markers in COMT and N0TCH4 gene were analyzed using the TDT in Chinese family trios. No preferential transmission of any allele or haplotype was detected for any of the polymorphisms studied. Subsequent association study did not demonstrate significant differences of genotype and allele frequency of studied polymorphisms between schizophrenics and controls in a large a case-control sample from China. These data suggest that COMT and N0TCH4 gene are unlikely to play a major role in the aetiology of schizophrenia in Han Chinese population. Our results also suggest that two VNTR polymorphisms of the 5-HTT gene and a single nucleotide polymorphism of PRODH gene are unlikely in linkage disequilibrium with a schizophrenia susceptibility gene in Han Chinese population.Future directions in schizophrenia genetics research include family-based linkage disequilibrium mapping based on large-scale genotyping of SNP markers and investigations of the epigenetic regulation of genes and the interaction between genes and environment variable may be necessary for complete understanding the genetic components to the aetiology of schizophrenia.