Li Dawei, He Lin
Bio-X Center, Shanghai Jiao Tong University, Shanghai 200030, China.
Schizophr Res. 2007 Nov;96(1-3):112-8. doi: 10.1016/j.schres.2007.05.017. Epub 2007 Jun 28.
Positional, functional and association studies have strongly implicated the dystrobrevin binding protein 1 gene (DTNBP1) as a promising novel candidate gene for schizophrenia. Since the first association study was reported, there have been many attempts to replicate it. However the results have been mixed and these subsequent studies have produced negative as well as positive results. To reconcile these conflicting findings and to give a comprehensive picture of the relationship of DTNBP1 and schizophrenia, the current meta-analysis combined all published association studies involving nine polymorphisms up to May 2006. The results (12 studies including 3429 cases, 3376 controls and 721 trios) showed that there were five single nucleotide polymorphisms (SNPs) with p values < 0.05, however, sensitivity analyses showed that only one SNP was consistent across all nine studies (four of the five SNPs became non-significant after removal of one study), indicating that one study may cause the association findings for each of these four SNPs. In conclusion, there is only a weak association of one SNP in DTNBP1 with schizophrenia, which is not significant after multiple testing.
定位、功能及关联性研究均有力地表明，肌萎缩蛋白结合蛋白1基因（DTNBP1）是精神分裂症颇具前景的新型候选基因。自首次报道关联性研究以来，已有多次重复该研究的尝试。然而，结果喜忧参半，后续研究既有阴性结果，也有阳性结果。为调和这些相互矛盾的研究结果，并全面呈现DTNBP1与精神分裂症之间的关系，当前的荟萃分析纳入了截至2006年5月所有已发表的涉及9种多态性的关联性研究。结果（12项研究，包括3429例病例、3376例对照和721个三联体）显示，有5个单核苷酸多态性（SNP）的p值<0.05，然而，敏感性分析表明，在所有9项研究中只有1个SNP是一致的（去除1项研究后，5个SNP中的4个变得不显著），这表明1项研究可能导致了这4个SNP各自的关联性研究结果。总之，DTNBP1中只有1个SNP与精神分裂症存在微弱关联，经多重检验后并不显著。
