Genetic Association Study of Schizophrenia using DNA microsatellite markers on chromosomes 19 and 20

作为全基因组关联研究的第一步，我们通过病例对照设计，寻找精神分裂症与19、20、21和22号染色体上的34个微卫星标记之间的关联。在日本人群中，168名精神分裂症患者和146名对照者被检查了相关性。34个位点的等位基因分布在日本和法国品种间差异显著。在对照受试者中，在S19 S209和D21 S1256观察到Hardy-Weingerg平衡的显著偏离。初步筛选的病例对照比较显示，D20 S95的等位基因频率和D20 S118的差异链存在显著差异。为了证实这些可能的关联，检查了由110名精神分裂症患者和116名对照组成的额外样本，并证实了D20 S95与精神分裂症之间的关联（Bonferroni校正后的校正P值为0.00035）。D20 S95与编码嗜铬粒蛋白B的基因CHGB位置相近，提示CHGB可能是一个参与痴呆症发生的重要候选基因。D20 S882位点比D20 S95更接近CHGB基因，病例对照比较结果支持这一假设。

As an intial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 controls in the Japanese population. The allele distribution of the 34 loci differed signficantly between Japanese and French opulations. Signficant deviation from the Hardy-Weingerg equilibrium was observed at S19S209 and D21S1256 in the control subjects. Case-control comparisons of the intial screeing revealed a significant difference in allele frequency at D20S95 and trand of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 controls were examined and an association between D20S95 and schizophrenia was confirmed (Corrected P value after the Bonferroni's correction was 0.00035). D20S95 is lacated close to the gene (CHGB) encoding chromogranin B.These findings suggest that CHGB could be an important candidate gene involved in the development of schizaphrenia. Results of the case-control comparison of the D20S882 locus, closer to the CHGB gene than D20S95 supported this hypothesis.