Family-Based Association Studies Of CAPON And Schizophrenia In The Chinese Han Population

Schizophrenia is a serious mental disorder that affects approximately 1% of the population with life-long devastating consequences. Many family, twin and adoption studies have demonstrated the role of genetic components in the etiology of schizophrenia. Currently there exist lots of hypothesis for the mechanism, among which the Glutamate neurotransmission hypothesis has received consistent attention, and some molecules in this pathway have been identified as susceptible genes for schizophrenia.CAPON (carboxyl-terminal PDZ ligand of the neuronal nitric oxide synthase), with its role in binding nitric oxide synthase, is placed at the centre of regulation of N-methyl-Daspartate (NMDA) receptor–mediated glutamate neurotransmission. Although there is evidence pointing to CAPON as a susceptible gene for schizophrenia, the results of independent association studies have so far been inconsistent. A recent case-control study supported CAPON as a susceptible site for the disease in the Chinese Han population. In their study both the single polymorphism (rs348624) and individual haplotypes showed significant association with schizophrenia. Our family-based association further investigates the relationship, which could avoid spurious results caused by population stratification. We selected 5 SNPs including rs348624 and performed a Transmission Disequilibrium Test (TDT) in 319 Chinese Han trios. Our results identified neither single marker nor haplotype associated with schizophrenia, which did not suggest that CAPON was a susceptible site in the Chinese Han population, or it appeared unlikely that the CAPON played a major role in the etiology of Schizophrenia.Our results may also simply reflect the problems of replication inherent in association studies of complex diseases, most of which have complex architectures, and the sum total of interactions between multiple genetic and environmental factors may play a more important role in susceptibility. Since there is consistent evidence pointing to 1q21-22 as a positional candidate region for schizophrenia, we suggest that further research should focus on other genes located in this region.