Department of Neuropsychiatry, Osaka Medical College, Osaka, Japan.
Behav Brain Funct. 2011 Oct 7;7:43. doi: 10.1186/1744-9081-7-43.
Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV.
Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors.
No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39).
The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.
精神分裂症是一种遗传性疾病，但尚未发现明确的遗传结构。为了克服这种不确定状态，SZGene 数据库已经建立，其中包括发表在同行评议期刊上的所有已发表的病例对照遗传关联研究。在本研究中，我们旨在确定 SZGene 强烈提示的遗传变异是否与我们的日本裔病例对照样本中的精神分裂症风险相关。此外，通过采用加性模型聚合七种变体的效应，我们旨在验证由操作性诊断手册 DSM-IV 诊断的精神分裂症的遗传异质性。
根据其 p 值对每个阳性提示的遗传多态性进行排名，然后从 DRD2、DRD4、GRIN2B、TPH1、MTHFR 和 DTNBP1 中选择七种排名最高的变体（p <0.0005）（2007 年 2 月）。407 例精神分裂症病例和 384 例对照参加了这项研究。为了根据参与者的遗传信息聚合疾病的易感性，我们通过添加遗传危险因素的数量计算了“风险指数”。
在基于排名最高的多态性的所有七种变体得出的遗传风险指数中，病例和对照组之间没有观察到统计学上的显著偏差。事实上，精神分裂症组（6.5+/-1.57）的平均风险指数得分略低于对照组（6.6+/-1.39）。
目前的工作说明了确定精神分裂症普遍和明确的风险赋予多态性的困难。我们使用的样本数量较小，因此不能排除这些变体中的一些或全部是日本人群中精神分裂症的次要风险因素。在进行复制工作时，还需要聚合 SZGene 数据库中更新的阳性变体。
