| 1 | J影响Disord 2013 151年10月:291 - 7 |
|---|---|
| PMID | 23820096 |
| Title | No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes. |
| Abstract | 尽管最近的全基因组关联研究已经确定了几种新的双相情感障碍（BD）风险变异，但结构成像研究报告了最一致的发现中的心室扩大和体积减少。我们研究了这些遗传风险变异是否可以解释BD中的某些结构性脑异常。 In a sample of 517 individuals (N=121 BD cases, 116 SZ cases, 61 other psychosis cases and 219 healthy controls), we tested the potential association between nine SNPs in the genes CACNA1C, ANK3, ODZ4 andSyne1and eight brain structural measures found to be altered in BD, and if these were specifically affecting the BD sample. We also assessed the polygenic effect of all these 9 SNPs on the brain phenotypes. 我们最重要的结果是CACNA1C SNP rs4775913中的风险等位基因A与总样本中小脑体积减少（Pnom。= 0.0075）之间的关联，在多次测试校正后（Pthreshold <0.0064）并不保持显着意义。BD组没有证据表明该关联的诊断特异性。此外，未观察到这9个SNP的多基因效应。 Low statistical power might increase our type II error rate. The present findings indicate that these risk SNPs do not explain a large proportion of the structural brain alterations in BD. Thus, these genes which are all related to neuronal functions must be involved in other pathophysiological aspects of BD development. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 2 | Ann. Hum. Genet. 2013 Nov 77: 504-12 |
| PMID | 23909765 |
| Title | Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs. |
| Abstract | A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including精神分裂症，在一个苏格兰家庭。Disc1是涉及大脑多种发育途径的蛋白质蛋白质相互作用网络的集线器蛋白。基于基因集的分析已被提出作为单个核苷酸多态性（SNP）单个分析的替代方法，以从全基因组关联研究中获取信息。在这项工作中，我们测试了基于以前的全基因组跨基因组关联的基因列表的最高结果，对二张蛋白质相互作用的蛋白质的分量过高精神分裂症。Our data set consisted of 5100 common missense SNPs genotyped in 476精神分裂症patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P-value=0.0158), indicative of the role of this gene set in精神分裂症风险。我们确定了七个前沿基因，MACF1，UTRN，DST，DISC1，KIF3A，Syne1，和AKAP9，负责过度代表。这些基因参与神经元细胞骨架组织和通过微管细胞骨架的细胞内转运，这表明这些过程在精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 3 | Ann. Hum. Genet. 2013 Nov 77: 504-12 |
| PMID | 23909765 |
| Title | Role of DISC1 interacting proteins in schizophrenia risk from genome-wide analysis of missense SNPs. |
| Abstract | A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including精神分裂症，在一个苏格兰家庭。Disc1是涉及大脑多种发育途径的蛋白质蛋白质相互作用网络的集线器蛋白。基于基因集的分析已被提出作为单个核苷酸多态性（SNP）单个分析的替代方法，以从全基因组关联研究中获取信息。在这项工作中，我们测试了基于以前的全基因组跨基因组关联的基因列表的最高结果，对二张蛋白质相互作用的蛋白质的分量过高精神分裂症。Our data set consisted of 5100 common missense SNPs genotyped in 476精神分裂症patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P-value=0.0158), indicative of the role of this gene set in精神分裂症风险。我们确定了七个前沿基因，MACF1，UTRN，DST，DISC1，KIF3A，Syne1，和AKAP9，负责过度代表。这些基因参与神经元细胞骨架组织和通过微管细胞骨架的细胞内转运，这表明这些过程在精神分裂症。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 4 | BMC Med. Genet. 2014 -1 15: 2 |
| PMID | 24387768 |
| Title | Genome-wide association study of bipolar disorder in Canadian and UK populations corroborates disease loci including SYNE1 and CSMD1. |
| Abstract | Recently, genome-wide association studies (GWAS) for cases versus controls using single nucleotide polymorphism microarray data have shown promising findings for complex neuropsychiatric disorders, including bipolar disorder (BD). 在这里，我们描述了一项全面的全基因组障碍研究（BD），对229个小家庭的基于家庭研究的交叉引用分析，其中有950多个病例的关联分析和来自英国和加拿大的950个种族匹配的对照。此外，在这些分析中鉴定出的基因座由通过样品的途径分析鉴定出来的途径。 Although no genome-wide significant markers were identified, the combined GWAS findings have pointed to several genes of interest that support GWAS findings for BD from other groups or consortia, such as atSyne1on 6q25, PPP2R2C on 4p16.1, ZNF659 on 3p24.3, CNTNAP5 (2q14.3), and CDH13 (16q23.3). This apparent corroboration across multiple sites gives much confidence to the likelihood of genetic involvement in BD at these loci. In particular, our two-stage strategy found association in both our combined case/control analysis and the family-based analysis on 1q21.2 (closest gene: sphingosine-1-phosphate receptor 1 gene, S1PR1) and on 1q24.1 near the gene TMCO1, and at CSMD1 on 8p23.2, supporting several previous GWAS reports for BD and for精神分裂症。Pathway analysis suggests association of pathways involved in calcium signalling, neuropathic pain signalling, CREB signalling in neurons, glutamate receptor signalling and axonal guidance signalling. The findings presented here show support for a number of genes previously implicated genes in the etiology of BD, including CSMD1 andSyne1, as well as evidence for previously unreported genes such as the brain-expressed genes ADCY2, NCALD, WDR60, SCN7A and SPAG16. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 5 | Commun Integr Biol 2014 -1 7: e28740 |
| PMID | 25053985 |
| Title | The role of F-actin in modulating Clathrin-mediated endocytosis: Lessons from neurons in health and neuropsychiatric disorder. |
| Abstract | Clathrin-mediated endocytosis is one of several mechanisms for retrieving transmembrane proteins from the cell surface. This key mechanism is highly conserved in evolution and is found in any eukaryotic cell from yeast to mammals. Studies from several model organisms have revealed that filamentous actin (F-actin) plays multiple distinct roles in shaping Clathrin-mediated endocytosis. Yet, despite the identification of numerous molecules at the interface between endocytic machinery and the cytoskeleton, our mechanistic understanding of how F-actin regulates endocytosis remains limited. Key insights come from neurons where vesicular release and internalization are critical to pre- and postsynaptic function. Recent evidence from human genetics puts postsynaptic organization, glutamate receptor trafficking, and F-actin remodeling in the spotlight as candidate mechanisms underlying neuropsychiatric disorders. Here I review recent findings that connect the F-actin cytoskeleton mechanistically to Clathrin-mediated endocytosis in the central nervous system, and discuss their potential involvement in conferring risk for neuropsychiatric disorder. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 6 | Front Neurosci 2014 -1 8：331 |
| PMID | 25414627 |
| Title | 与主要神经精神疾病相关的常见和不同遗传成分的神经信息分析。 |
| Abstract | Major neuropsychiatric disorders are highly heritable, with mounting evidence suggesting that these disorders share overlapping sets of molecular and cellular underpinnings. In the current article we systematically test the degree of genetic commonality across six major neuropsychiatric disorders-attention deficit hyperactivity disorder (ADHD), anxiety disorders (Anx), autistic spectrum disorders (ASD), bipolar disorder (BD), major depressive disorder (MDD), and精神分裂症(SCZ). We curated a well-vetted list of genes based on large-scale human genetic studies based on the NHGRI catalog of published genome-wide association studies (GWAS). A total of 180 genes were accepted into the analysis on the basis of low but liberal GWAS p-values (<10(-5)). 22% of genes overlapped two or more disorders. The most widely shared subset of genes-common to five of six disorders-included ANK3, AS3MT, CACNA1C, CACNB2, CNNM2, CSMD1, DPCR1, ITIH3, NT5C2, PPP1R11,Syne1, TCF4, TENM4, TRIM26, and ZNRD1. Using a suite of neuroinformatic resources, we showed that many of the shared genes are implicated in the postsynaptic density (PSD), expressed in immune tissues and co-expressed in developing human brain. Using a translational cross-species approach, we detected two distinct genetic components that were both shared by each of the six disorders; the 1st component is involved in CNS development, neural projections and synaptic transmission, while the 2nd is implicated in various cytoplasmic organelles and cellular processes. Combined, these genetic components account for 20-30% of the genetic load. The remaining risk is conferred by distinct, disorder-specific variants. Our systematic comparative analysis of shared and unique genetic factors highlights key gene sets and molecular processes that may ultimately translate into improved diagnosis and treatment of these debilitating disorders. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 7 | Curr Psychiatry Rep 2014 Nov 16: 493 |
| PMID | 25194313 |
| Title | New developments in the genetics of bipolar disorder. |
| Abstract | 在过去的几年中，这是双相情感障碍（BPD）遗传学的突破性，因为该领域首次确定了强大的风险变异。领先的是全基因组关联研究（GWAS），这些研究已经评估了非常大的患者和对照组的常见遗传标记。这些导致了包括ANK3，CACNA1C在内的基因的发现Syne1, ODZ4, and TRANK1. Additional studies have begun to examine the biology of these genes and how risk variants influence aspects of brain and behavior that underlie BPD. For example, carriers of the CACNA1C risk variant have been found to exhibit hippocampal and anterior cingulate dysfunction during episodic memory recall. This work has shed additional light on the relationship of bipolar susceptibility variants to other disorders, particularly精神分裂症。预计甚至有21,035例病例和28,758个对照的样品，预计BPD GWAS甚至更大。研究通过锂反应的研究检查了BPD的药物基因组学，得出了尚待证实的备受瞩目的结果。该领域的下一个边界是通过大规模DNA测序鉴定稀有的双极敏感性变体。迄今为止，尽管只发表了几篇论文，但仍在进行许多研究。已经形成了双极测序联盟，以将所有在该区域工作的组汇总在一起，并执行生成的数据的荟萃分析。该财团拥有13个成员组，现在拥有〜3500例案例和约5,000个对照的外部数据，以及约162个家庭。随着获得此类数据的成本继续下降，重点可能会在几年内从外显子数据转变为整个基因组数据。现在，基因图研究提供了明确的结果，可以洞悉该疾病的病理生理学。测序研究应进一步扩展此过程。 Findings could eventually set the stage for rational therapeutic development. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 8 | Mol. Cell. Neurosci. 2016 Mar 71: 46-55 |
| PMID | 26704904 |
| Title | Genomic mapping and cellular expression of human CPG2 transcripts in the SYNE1 gene. |
| Abstract | 躁郁症（BD）是一种普遍且严重的情绪障碍，其特征是躁狂和抑郁症的复发发作。遗传因素和环境因素都与BD病因有关，但生物学基础仍然难以捉摸。最近全基因组关联研究（GWAS），用于鉴定赋予风险的基因精神分裂症, BD, and major depression, identified an association between single-nucleotide polymorphisms (SNPs) in theSyne1gene and increased risk of BD.Syne1has also been identified as a risk locus for multiple other neurological or neuromuscular genetic disorders. The BD associated SNPs map within the gene region homologous to part of ratSyne1涵盖编码CPG2的大脑特异性转录本，这是一种局限于兴奋性突触的突触后神经元蛋白和谷氨酸受体内在化的重要调节剂。在这里，我们使用RNA-Seq，Chip-Seq和Race绘制人类Syne1转录组,关注CPG2轨迹。我们瓦里date several CPG2 transcripts, including ones not previously annotated in public databases, and identify and clone a full-length CPG2 cDNA expressed in human neocortex, hippocampus and striatum. Using lenti-viral gene knock down/replacement and surface receptor internalization assays, we demonstrate that human CPG2 protein localizes to dendritic spines in rat hippocampal neurons and is functionally equivalent to rat CPG2 in regulating glutamate receptor internalization. This study provides a valuable gene-mapping framework for relating multiple genetic disease loci inSyne1with their transcripts, and for evaluating the effects of missense SNPs identified by patient genome sequencing on neuronal function. |
| SCZ Keywords | 精神分裂症，精神分裂症 |