| 1 | Mol. Psychiatry 2006 May 11: 471-8 |
|---|---|
| PMID | 16402134 |
| 标题 | Identification of the semaphorin receptor PLXNA2 as a candidate for susceptibility to schizophrenia. |
| 抽象的 | 这discovery of genetic factors that contribute toschizophrenia易感性是理解该疾病病因的关键挑战。在这里，我们报告了小说的识别schizophrenia染色体1q32，plexin A2上的候选基因（PLXNA2), in a genome-wide association study using 320 patients withschizophreniaof European descent and 325 matched controls. Over 25,000 single-nucleotide polymorphisms (SNPs) located within approximately 14,000 genes were tested. Out of 62 markers found to be associated with disease status, the most consistent finding was observed for a candidate locus on chromosome 1q32. The marker SNP rs752016 showed suggestive association withschizophrenia（优势比（OR）= 1.49，p = 0.006）。在欧洲人的独立病例对照样本中证实了这一结果（合并OR = 1.38，p = 0.035），在拉丁美洲人（OR = 1.26）和亚裔美国人（OR = 1.37）中观察到了类似的遗传效应。还从两个基于家庭的集合中获得了支持证据，其中一个收集达到统计显着性（OR = 2.2，p = 0.02）。高密度SNP映射表明，关联区域跨度约为60 kbPLXNA2基因。14个SNP基因分型中的8个在病例和对照之间显示出统计学上的显着差异。这些结果符合以前确定染色体1q32染色体为候选区域的遗传发现schizophrenia。PLXNA2是跨膜信号素受体家族的成员，在发育过程中参与轴突引导，并可能调节神经元的可塑性和再生。这PLXNA2ligand semaphorin 3A has been shown to be upregulated in the cerebellum of individuals withschizophrenia。这se observations, together with the genetic results, makePLXNA21Q32的可能候选人schizophrenia易感基因座。 |
| SCZ关键字 | schizophrenia |
| 2 | Arch. Gen. Psychiatry 2007 Mar 64: 318-26 |
| PMID | 17339520 |
| 标题 | Anxiety and comorbid measures associated with PLXNA2. |
| 抽象的 | 已经提出了成年神经发生的减少，作为抑郁症发作的一种机制。信号蛋白及其共感受器丛蛋白已与神经系统发育和成人神经发生有关。最近的全基因组协会研究schizophrenia确定了编码丛蛋白A2的基因的变体（PLXNA2）在研究样本中最始终如一。已经报道了精神病和心理学措施之间的常见遗传负债，但很少有常见遗传变异的例子。 To perform a genetic association study between 6 single nucleotide polymorphisms from thePLXNA2gene (rs3736963, rs2767565, rs752016, rs1327175, rs2478813, and rs716461) and anxiety, depression, neuroticism, and psychological distress. 极端不一致和一致的兄弟姐妹。 Australia. Study participants were selected with respect to extreme neuroticism scores from a population cohort of 18 742 twin individuals and their siblings. The participants and their parents (if blood or buccal samples were available) were genotyped, for a total of 2854 genotyped individuals from 990 families. Of these, 624 individuals with a diagnosis of anxiety or depression from 443 families were used in the association analysis. All the participants completed the Composite International Diagnostic Interview, the 23-item Neuroticism scale of the revised Eysenck Personality Questionnaire, and the 10-item Kessler Psychological Distress Scale. Diagnoses of DSM-IV depression and anxiety were determined from the Composite International Diagnostic Interview. 有证据表明RS2478813（以及其他单核苷酸多态性与之相关）与焦虑，抑郁，神经质和心理困扰之间存在等位基因关联；在Bonferroni校正多次测试后，与焦虑的关联是显着的（经验P <.001）。老鼠的直系同源PLXNA2位于先前报道的小鼠焦虑的非常重要的连锁区域中。 PLXNA2是通过合并症与焦虑症的合并症焦虑和其他精神疾病的因果变异的候选者。 |
| SCZ关键字 | schizophrenia |
| 3 | prog。神经心理药物。生物。精神病学2007年5月31日：873-7 |
| PMID | 17346868 |
| 标题 | 未能证实日本人群中PLXNA2基因与精神分裂症之间的关联。 |
| 抽象的 | Plexins are receptors for multiple classes of semaphorins, either alone or in combination with neuropilins. Plexins participate in many cellular events that include axonal repulsion, axonal attraction, cell migration, axon pruning, and synaptic plasticity.PLXNA2地图至染色体1Q32。几项连锁研究报道了schizophrenia1q22-42区域的敏感位点。最近的一项研究报告说，内含子的单核苷酸多态性（SNP）PLXNA2与之相关schizophrenia在欧美人口中。我们试图在日本的336例患者中复制这一发现schizophrenia和304个控件。此外，我们研究了3个非同义SNP（Arg5GLN，GLN57ARG和ALA267THR）PLXNA2。基因分型是由Taqman等位基因歧视测定法进行的。患者和对照组之间的4个内含子SNP或3个非同义SNP的基因型或等位基因分布没有显着差异。此外，基于单倍型的分析没有提供关联的证据。这些结果表明PLXNA2可能不会在发展中发挥重要作用schizophrenia在我们的日本样本中。 |
| SCZ关键字 | schizophrenia |
| 4 | Nat. Genet. 2008 Jul 40: 827-34 |
| PMID | 18583979 |
| 标题 | 精神分裂症的遗传关联研究的系统荟萃分析和现场概要：SZGENE数据库。 |
| 抽象的 | 为了查明潜在的遗传危险因素schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies forschizophrenia('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR,PLXNA2，SLC6A4，TP53和TPH1）名义上具有显着影响，平均汇总优势比约为1.23。这些变体中的七种以前未被荟萃分析。根据最近提出的评估遗传关联研究累积证据的标准，可以将四个重要结果表征为“强”流行病学信誉。我们的项目代表了系统合成和分级的遗传关联研究证据的首个综合在线资源schizophrenia。As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders. |
| SCZ关键字 | schizophrenia |
| 5 | 精神分裂。res。2008年2月99日：359-64 |
| PMID | 18065206 |
| 标题 | Genetic examination of the PLXNA2 gene in Japanese and Chinese people with schizophrenia. |
| 抽象的 | 异常神经发展是病因的综合理论之一schizophrenia。plexin a2（PLXNA2）基因是轴突引导因素的受体基因之一。最近，来自四个单核苷酸多态性（SNP），RS841865，RS752016，RS1327175和RS2498028PLXNA2据报道，基因组间隔与schizophrenia在欧洲人，拉丁美洲和亚裔美国人的样本中。我们在两个亚洲人群中测试了这四个SNP与疾病的关联：1140个病例对照日本样本和293个中国血统（1163个样本）。在日本样品中，在病例和对照组之间观察到了rs841865的等位基因频率和基因型分布的显着差异（分别为p = 0.019和0.020）。单倍型分析还揭示了该基因与该疾病的显着关联（全局P = 0.028）。相反，没有PLXNA2向中国人schizophrenia，通过连锁分析或关联测试（等位基因和单倍型传输不平衡测试）。这些发现表明PLXNA2赋予不同的遗传风险schizophreniaamong different populations. |
| SCZ关键字 | schizophrenia |
| 6 | J Psychiatr Res 2011 Jan 45：47-53 |
| PMID | 20684831 |
| 标题 | 信号素3D基因（SEMA3D）与精神分裂症的可能关联。 |
| 抽象的 | 信号素是丛蛋白的配体，丛肌蛋白信号传导系统广泛参与许多神经元事件，包括轴突引导，细胞迁移，轴突修剪和突触可塑性。plexin A2基因（PLXNA2据报道）schizophrenia。This finding prompted us to examine the possible association between the semaphorin 3D gene (SEMA3D) andschizophreniain a Japanese population. We genotyped 9 tagging single nucleotide polymorphisms (SNPs) of SEMA3D including a non-synonymous variation, Lys701Gln (rs7800072), in a sample of 506 patients withschizophrenia和941个健康对照受试者。GLN701等位基因对开发具有显着的保护作用schizophrenia(p�=�0.0069, odds ratio�=�0.76, 95% confidence interval 0.63 to 0.93). Furthermore, the haplotype-based analyses revealed a significant association. The four-marker analysis (rs2190208-rs1029564-rs17159614-rs12176601), in particular, not including the Lys701Gln, revealed a highly significant association (p�=�0.00001, global permutation), suggesting that there may be other functional polymorphisms within SEMA3D. Our findings provide strong evidence that SEMA3D confers susceptibility toschizophrenia，这可能导致该疾病的神经发育障碍。 |
| SCZ关键字 | schizophrenia |
| 7 | 翻译精神病学2012 -1 2：E113 |
| PMID | 22832957 |
| 标题 | Association between SNPs and gene expression in multiple regions of the human brain. |
| 抽象的 | 鉴定DNA变异（单核苷酸多态性（SNP））和脑组织中的基因表达之间的遗传CIS关联可能是找到有助于有助于精神疾病病因的功能相关途径的一种有希望的方法。在这项研究中，我们检查了额叶皮层，海马，颞皮层，丘脑和小脑在患有精神疾病和正常对照的受试者中的遗传变异与基因表达之间的关联。我们确定了各个大脑区域中648个转录本和6725个SNP之间的CIS关联。几个SNP显示出大脑区域特异性关联。在此处测试的所有大脑区域中，仅一个基因PDE4DIP的表达水平与SNP RS12124527相关。从我们的数据中，我们生成了脑顺式表达定量特质基因座（EQTL）基因的列表，我们将schizophreniacandidate genes downloaded from theschizophrenia论坛(SZgene)数据库(http://www.szgene.org/)。Of the SZgene candidate genes, we found that the expression levels of four genes, HTR2A,PLXNA2, SRR and TCF4, were significantly associated with cis SNPs in at least one brain region tested. One gene, SRR, was also involved in a coexpression module that we found to be associated with disease status. In addition, a substantial number of cis eQTL genes were also involved in the module, suggesting eQTL analysis of brain tissue may identify more reliable susceptibility genes forschizophrenia比病例对照遗传关联分析。为了促进遗传变异可能是主要精神疾病病因的基础的遗传变异，我们将大脑EQTL结果纳入了公共和在线数据库，Stanley Neuropatium Integrortium Integrortife Integrative Database（SNCID; http; http; http; /sncid.stanleyresearch。beplay苹果手机能用吗org）。 |
| SCZ关键字 | schizophrenia |