| 1 | Mol. Psychiatry 2009 Mar 14: 252-60 |
|---|---|
| PMID | 19065143 |
| Title | Gene-wide analyses of genome-wide association data sets: evidence for multiple common risk alleles for schizophrenia and bipolar disorder and for overlap in genetic risk. |
| Abstract | Genome-wide association (GWAS) analyses have identified susceptibility loci for many diseases, but most risk for any complex disorder remains unattributed. There is therefore scope for complementary approaches to these data sets. Gene-wide approaches potentially offer additional insights. They might identify association to genes through multiple signals. Also, by providing support for genes rather than single nucleotide polymorphisms (SNPs), they offer an additional opportunity to compare the results across data sets. We have undertaken gene-wide analysis of two GWAS data sets:精神分裂症and bipolar disorder. We performed two forms of analysis, one based on the smallest P-value per gene, the other on a truncated product of P method. For each data set and at a range of statistical thresholds, we observed significantly more SNPs within genes (P(min) for excess<0.001) showing evidence for association than expected whereas this was not true for extragenic SNPs (P(min) for excess>0.1). At a range of thresholds of significance, we also observed substantially more associated genes than expected (P(min) for excess in精神分裂症= 1.8 x 10(8),在双= 2.4 x 10(6))。此外,an excess of genes showed evidence for association across disorders. Among those genes surpassing thresholds highly enriched for true association, we observed evidence for association to genes reported in other GWAS data sets (CACNA1C) or to closely related family members of those genes including CSF2RB,CACNA1B和DGKI。我们的分析表明，关联信号在基因和周围周围富集，大量基因构成疾病和全基因分析，为更多标准方法提供了有用的互补方法。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 2 | Proc. Natl. Acad. Sci. U.S.A. 2010 Jun 107: 10584-9 |
| PMID | 20489179 |
| Title | Strong synaptic transmission impact by copy number variations in schizophrenia. |
| Abstract | 精神分裂症是一种精神疾病，在青春期后发作，病因不清，具有正症状和阴性症状以及认知缺陷。确定拷贝数变化（CNV），以增加精神分裂症，我们对977的队列进行了全基因组CNV分析精神分裂症病例和2,000名健康的欧洲血统成年人，他们经过170万探针的基因分型。在758的独立队列中评估了积极发现精神分裂症病例和1,485个对照。在病例中，基因本体论突触传递家族显然富含CNV（p = 1.5 x 10（-7））。在这些当中，CACNA1Band DOC2A, both calcium-signaling genes responsible for neuronal excitation, were deleted in 16 cases and duplicated in 10 cases, respectively. In addition, RET and RIT2, both ras-related genes important for neural crest development, were significantly affected by CNVs. RET deletion was exclusive to seven cases, and RIT2 deletions were overrepresented common variant CNVs in the精神分裂症案例。我们的结果表明，涉及突触传播过程的新型变化有助于精神分裂症。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 3 | J. Neurogenet. 2010 Dec 24: 182-93 |
| PMID | 20615089 |
| Title | ？ - 连接蛋白启动子芯片芯片揭示了潜在的精神分裂症和躁郁症基因网络。 |
| Abstract | 锂盐的治疗浓度抑制糖原合酶激酶3β（GSK3？）和磷酸肌醇（PI）信号表明这些途径异常激活可能是双极疾病（BD）病理生理学的因素。这些途径的参与也得到了最近全基因组关联研究（GWASS）的支持。研究人员研究了BD的分子基础，锂的治疗作用是通过微阵列表达研究，因为GSK3？ - 以及PI介导的信号转导途径均与转录激活和抑制耦合。但是，表达分析有一些局限性，研究者无法使用该方法来分析胎儿脑组织，这可以说是与基于遗传性精神疾病的发展有关的最相关的生物结构。为了解决这些缺点，作者采用了一种新颖的方法，使用了染色质免疫沉淀的材料，将富含的材料退火到微阵列（CHIP-CHIP）靶向基因的胎儿脑组织中，由？ - 卡宁蛋白结合在一起，这是由GSK3？直接调节的转录因子。发现640个基因的启动子被绑定吗？ - 蛋白酶，其中许多已知精神分裂症(SZ), autism spectrum disorder (ASD), and BD candidates, includingCACNA1B，NRNG，SNAP29，FGFR1，PCDH9和九个在最近发表的GWASS和全基因组搜索副本编号变体（CNV）中发现的其他九个。研究结果表明，SZ和BD的看似不同的候选基因可以纳入围绕GSK3？/？ - catenin信号传导的共同分子网络中。此外，假定的锂响应途径可能影响SZ和ASD候选基因的亚组可能具有治疗意义。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 4 | Psychiatr. Genet. 2011 Feb 21: 1-4 |
| PMID | 21057379 |
| Title | 病例案例基因组的关联分析显示标记与精神分裂症和躁郁症差异相关，并暗示钙通道基因。 |
| Abstract | There are theoretical reasons why comparing marker allele frequencies between cases of different diseases, rather than with controls, may offer benefits. The samples may be better matched, especially for background risk factors common to both diseases. Genetic loci may also be detected which influence which of the two diseases occurs if common risk factors are present. 我们使用了英国双极的样品精神分裂症较早进行了全基因组关联研究的病例并比较了两个样品之间的标记等位基因频率。当标记有所不同时，我们将案例样品等位基因频率与对照样品的频率进行了比较。 八个标记在p值小于10（-5）时具有显着意义。其中，最有趣的发现是RS17645023，其p值小于10（-6）的p值显着，并且来自CACNG5的36 kb。该标记的对照等位基因频率中间是双极性和精神分裂症案例。 The application of this approach suggests that it does have some merits. The finding for CACNG5, taken together with the earlier implication of CACNA1C andCACNA1B，强烈建议在对双相情感障碍和/或精神分裂症。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 5 | Psychiatr. Genet. 2011 Feb 21: 1-4 |
| PMID | 21057379 |
| Title | 病例案例基因组的关联分析显示标记与精神分裂症和躁郁症差异相关，并暗示钙通道基因。 |
| Abstract | There are theoretical reasons why comparing marker allele frequencies between cases of different diseases, rather than with controls, may offer benefits. The samples may be better matched, especially for background risk factors common to both diseases. Genetic loci may also be detected which influence which of the two diseases occurs if common risk factors are present. 我们使用了英国双极的样品精神分裂症较早进行了全基因组关联研究的病例并比较了两个样品之间的标记等位基因频率。当标记有所不同时，我们将案例样品等位基因频率与对照样品的频率进行了比较。 八个标记在p值小于10（-5）时具有显着意义。其中，最有趣的发现是RS17645023，其p值小于10（-6）的p值显着，并且来自CACNG5的36 kb。该标记的对照等位基因频率中间是双极性和精神分裂症案例。 The application of this approach suggests that it does have some merits. The finding for CACNG5, taken together with the earlier implication of CACNA1C andCACNA1B，强烈建议在对双相情感障碍和/或精神分裂症。 |
| SCZ Keywords | 精神分裂症, schizophrenic |
| 6 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2016 Mar 171: 181-202 |
| PMID | 26462458 |
| Title | 目前公认的精神分裂症基因：高分辨率染色体意识形态图。 |
| Abstract | A large body of genetic data from精神分裂症- 相关研究已经确beplay苹果手机能用吗定了各种基因和干扰的途径，支持复杂遗传成分参与精神分裂症频谱和其他精神病。遗传技术的进步和通过可搜索的基因组数据库扩大研究的扩展导致了多个已发表的报告，使我们能够汇编已知的，临床相关或易感基因的主列表，从而有助于精神分裂症。We searched key words related to精神分裂症以及来自同行评审的医学文献来源，权威公共访问精神病网站和基因组数据库的遗传学，专门用于基因发现和表征精神分裂症。我们的560个基因列表以字母顺序排列为表格形式，并放置在高分辨率人类染色体意识形态上的基因符号。在最终的基因列表上进行了基因组广泛的途径分析，以评估基础遗传结构精神分裂症。Recognized genes of clinical relevance, susceptibility or causation impact a broad range of biological pathways and mechanisms including ion channels (e.g.,CACNA1B, CACNA1C, CACNA1H), metabolism (e.g., CYP1A2, CYP2C19, CYP2D6), multiple targets of neurotransmitter pathways impacting dopamine, GABA, glutamate, and serotonin function, brain development (e.g., NRG1, RELN), signaling peptides (e.g., PIK3CA, PIK4CA) and immune function (e.g., HLA-DRB1, HLA-DQA1) and interleukins (e.g., IL1A, IL10, IL6). This summary will enable clinical and laboratory geneticists, genetic counselors, and other clinicians to access convenient pictorial images of the distribution and location of contributing genes to inform diagnosis and gene-based treatment as well as provide risk estimates for genetic counseling of families with affected relatives. � 2015 Wiley Periodicals, Inc. |
| SCZ Keywords | 精神分裂症, schizophrenic |