Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, 10110, Thailand.
Behav Brain Funct. 2012 May 29;8:27. doi: 10.1186/1744-9081-8-27.
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 ± 6.0 years, 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.
全基因组关联研究(GWAS)结合脑成像作为一种定量特征分析,揭示了 CTXN3-SLC12A2 区域附近的 SNP 与前脑发育和应激反应有关,而这些反应涉及精神分裂症。在本研究中,分析了该区域的 SNP 与泰国人群精神分裂症的关联。
共纳入 115 例精神分裂症患者和 173 例无关的正常对照,平均年龄分别为 37.87±11.8 和 42.81±6.0 岁。采用聚合酶链反应和高分辨率熔解(HRM)分析进行基因分型。使用 SPSS 软件的卡方检验评估患者和对照组之间基因型分布的差异。
我们发现 GWAS 发现的 SNP rs245178 与泰国人群精神分裂症的风险之间存在显著关联[P=0.006,次要 G 等位基因的优势比:0.62(0.46-0.83)]。此外,与 rs245178 中度连锁不平衡的另一个潜在 SNP rs698172 也与精神分裂症强烈相关[P=0.003,次要 T 等位基因的优势比:0.61(0.46-0.82)]。在进行多重检验的 Bonferroni 校正后,这种关联仍然具有统计学意义。
本研究表明,CTXN3 和 SLC12A2 基因间的两个 SNP rs245178 和 rs698172 与泰国人群精神分裂症的风险相关。需要进一步研究这些 SNP 周围的遗传变异在 CTXN3 和 SLC12A2 基因表达模式中的作用,这可能与精神分裂症的发病机制有关。