| 1 | PLoS ONE 2013 -1 8: e67776 |
|---|---|
| PMID | 23922650 |
| Title | Association study of 167 candidate genes for schizophrenia selected by a multi-domain evidence-based prioritization algorithm and neurodevelopmental hypothesis. |
| Abstract | 来自多个领域的综合证据可用于优先考虑候选疾病基因进行随后的测试。在爱尔兰高密度研究中，我们在连锁峰下对所有已知的人类基因（n = 3819）进行了排名精神分裂症使用三个不同证据域的家庭：1）使用斯坦利脑收集的微阵列基因表达结果的荟萃分析，2）a精神分裂症蛋白质 - 蛋白质相互作用网络和3）系统文献搜索。每个基因都被分配一个特异性的p值，并在评估每个域内的证据后进行排名。为了与此排名过程进行比较，还通过包括具有与神经发育相关的基因本体术语的基因来测试大规模候选基因假说。随后，使用自定义Illumina Iselect阵列中的167个基因中3725个SNP的基因型用于评估最高排名与假设选定的基因。七十三个基因既高度排名又参与神经发育（类别1），而42个基因和52个基因分别是神经发育（类别2）或高度排名（类别3）。在PRKG1，PRKCE和CNTN4but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of精神分裂症showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted. |
| SCZ关键字 | 精神分裂症 |
| 2 | Invest. Ophthalmol. Vis. Sci. 2014 May 55: 3258-64 |
| PMID | 24764060 |
| Title | Gene-rich large deletions are overrepresented in POAG patients of Indian and Caucasian origins. |
| Abstract | 大拷贝数变化（CNV）可能会导致神经退行性疾病的负担增加。在这项研究中，我们分析了一开始的开头青光眼（POAG）的大型CNV> 100 kb的全基因组负担，这是眼睛的神经退行性疾病，是不可逆失明的最大原因。 Genome-wide analysis of CNVs > 100 kb were analyzed in a total of 1720 individuals, including an Indian cohort (347 POAG cases and 345 controls) and a Caucasian cohort (624 cases and 404 controls). All the CNV data were obtained from experiments performed on Illumina 660W-Quad (infinium) arrays. 我们观察到，对于两个人群，CNV> 1 Mb在POAG病例中独有的富基因区域显着富集（p <10（-11））。在印度队列中，CNV> 1 MB（39个呼叫）在患者中影响了125个基因，而对照31中，这种CNV仅影响5个基因，没有重叠。在这两个队列中，我们观察到与重复相比，缺失患者的1.9倍基因富集，而在对照组中未观察到这种偏见（0.3倍）。总体重复> 1 MB超过缺失（DEL/DUP = 0.82），证实患者富含基因的缺失与该疾病有关。在印度患者的39个CNV> 1 MB中，有28名（72％）也与其他神经退行性疾病有关，例如自闭症，精神分裂症, sensorineural hearing loss, and so forth. We found one large duplication encompassingCNTN4gene in Indian and Caucasian POAG patients that was absent in the controls. To our knowledge, our study is the first report on large CNV bias for gene-rich regions in glaucomatous neurodegeneration, implicating its impact across populations of contrasting ethnicities. We identifiedCNTN4as a novel candidate gene for POAG. |
| SCZ关键字 | 精神分裂症 |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2015 Dec 168: 649-59 |
| PMID | 26198764 |
| Title | 基因组全基因组协会的精神分裂症研究中的阿什凯纳济犹太人。 |
| Abstract | 精神分裂症是一种常见的，临床上异质性的疾病，与终生发病率和早期死亡率有关。与精神分裂症已经确定了，但大多数遗传力仍然未知。在这项研究中，我们报告了Ashkenazi犹太人（AJ）的病例对照样本，该样本可能会提供有关对遗传病因学的更多见解精神分裂症。We performed a genome-wide association analysis (GWAS) of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently, we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640 controls, followed by a meta-analysis and polygenic risk scoring using summary results from Psychiatric GWAS Consortium 2精神分裂症学习。美国AJ样品显示了多基因遗传（伪R（2）？9.7％）和SNP可耐性估计值为0.39（p？=？0.00046）。我们发现在美国样本或联合美国/以色列AJ荟萃分析中，没有发现全基因组的显着关联，对1505例病例和2145例对照。最强的AJ特异性关联（10（-6）-10（-7）范围内的P值在22q 11.2缺失区域中，包括基因TBX1，GLN1和COMT。支持证据（meta p？CNTN4，IMMP2L和Grin2a。PGC2结果对美国样本的荟萃分析为六个新基因座提供了最初的全基因组的重要证据。在新型潜在的敏感性基因中，PEPD是参与脯氨酸代谢的基因，该基因与以发育延迟和认知缺陷为特征的孟德尔疾病有关。 |
| SCZ关键字 | 精神分裂症 |
| 4 | J Neurodev Disord 2015 -1 7：26 |
| PMID | 26257835 |
| Title | CNTN6 copy number variations in 14 patients: a possible candidate gene for neurodevelopmental and neuropsychiatric disorders. |
| Abstract | Neurodevelopmental disorders are impairments of brain function that affect emotion, learning, and memory. Copy number variations of contactin genes (CNTNs), including CNTN3,CNTN4, CNTN5, and CNTN6, have been suggested to be associated with these disorders. However, phenotypes have been reported in only a handful of patients with copy number variations involving CNTNs. 从2009年1月到2013年1月，通过匹兹堡大学医学中心确定的3724名患者被转交给我们的临床阵列比较基因组杂交测试的实验室。我们筛选了这些患者队列，以识别涉及CNTN6基因的3P26.3拷贝数变化的个体，然后回顾性地审查了这些患者的临床信息和家族病史，以确定3p26.3拷贝数变化与神经发育障碍之间的关联。 3724例患者中有14例具有3P26.3涉及CNTN6基因的拷贝数变化。这些CNTN6拷贝数变化的14例患者中有13例出现各种神经发育障碍，包括发育延迟，自闭症频谱障碍，癫痫发作和注意力缺陷多动障碍。在14例患者中，有13例可以使用家族史。十三个家庭中有十二个有多个患有神经发育和神经精神疾病的成员精神分裂症, depression, anxiety, learning disability, and bipolar disorder. 我们的发现表明，CNTN6基因的删除或重复与广泛的神经发育行为障碍有关。 |
| SCZ关键字 | 精神分裂症 |
| 5 | 摩尔。神经生物醇。2016年4月1日：-1 |
| PMID | 27052956 |
| Title | Polymorphism of rs3737597 in DISC1 Gene on Chromosome 1q42.2 in sALS Patients: a Chinese Han Population Case-Control Study. |
| Abstract | 尽管已经揭示了许多基因与零星营养性侧索硬化症（SALS）有关，但仍需要进一步探索其遗传机制。我们旨在搜索萨尔的新遗传因素并评估其贡献。我们基于3227个重要基因（P值？精神分裂症-1 (DISC1),CNTN4, NRXN3, and ERBB4) presented a considerable association with sALS in both studies. To further verify the association between the NSD function target genes and sALS, we preformed a two-stage case-control study based on 500 sALS patients and 500 controls of Chinese Han populations from mainland. A polymorphism of rs3737597 in DISC1 gene involved in the nervous system developmental pathway was closely associated with sALS. The nervous system developmental pathway is a potential pathogenesis of sALS, among them, the polymorphism of rs3737597 in DISC1 might play some roles. |
| SCZ关键字 | 精神分裂症 |
| 6 | J Neurodev Disord 2016 -1 8: 6 |
| PMID | 26958094 |
| Title | CNTN4突变对自闭症相关性状的影响有限，而成人C57BL/6J小鼠的影响有限。 |
| Abstract | Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence ofCNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4）关于不同发育阶段的神经，感觉，认知和行为表型。 C57BL/6J mice with heterozygous and homozygous disruption ofCNTN4通过在各个发育阶段进行广泛的，部分纵向测试的电池进行了研究，包括各种范式测试社交和受限重复行为。 Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged inCNTN4-deficient versus wild-type mice. The impact ofCNTN4- 缺陷被发现仅限于在杂合和纯合的不同高幅度的听觉刺激后，令人惊叹的反应能力提高CNTN4缺乏的老鼠和增强收购在争吵ial learning task in homozygous mice. 破坏CNTN4在C57BL/6J背景中，在发育或成年小鼠中不影响特定自闭症相关的表型，但会导致感觉行为反应和认知性能的微妙非犯罪特定变化。 |
| SCZ关键字 | 精神分裂症 |