A genome-wide association study (GWAS) combined with brain imaging as a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region were related to forebrain development and stress response which involved in schizophrenia. In the present study, the SNPs in this region were analyzed for association with schizophrenia in a Thai population.
A total of 115 schizophrenia and 173 unrelated normal controls with mean age of 37.87±11.8 and 42.81±6.0years, respectively, were included in this study. Genotyping was performed using polymerase chain reaction and high-resolution melting (HRM) analysis. The difference in genotype distribution between patient and control was assessed by Chi-square test of the SPSS software.
We found a significant association between the GWAS-discovered SNP, rs245178, with the risk of schizophrenia in the Thai population [P=0.006, odds ratio for the minor G allele: 0.62(0.46–0.83)]. Additionally, another potential SNP, rs698172, which was in moderate linkage disequilibrium with rs245178, also showed strong association with schizophrenia [P=0.003, odds ratio for minor T allele: 0.61(0.46–0.82)]. This association remained significant at 5% level after the Bonferroni correction for multiple testing.
This study shows that two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are associated with risk of schizophrenia in Thai population. Further study is required for clarification the role of genetic variation around these SNPs in expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in schizophrenia pathogenesis.
Keywords: Schizophrenia, Single nucleotide polymorphisms, CTXN3, SLC12A2, High- resolution melting analysis