| 1 | Behav Brain Funct 2013 -1 9: 40 |
|---|---|
| PMID | 24160291 |
| Title | The impact of the genome-wide supported variant in the cyclin M2 gene on gray matter morphology in schizophrenia. |
| Abstract | Genome-wide significant associations ofschizophreniawith eight SNPs in theCNNM2, MIR137, PCGEM1, TRIM26, CSMD1, MMP16, NT5C2 and CCDC68 genes have been identified in a recent mega-analysis of genome-wide association studies. To date, the role of these SNPs on gray matter (GM) volumes remains unclear. 使用JPT HAPMAP样品和我们的样品进行了小方便频率的质量控制？>？5％，基因分型呼叫率？>？95％和Hardy-Weinberg平衡测试（P？>？0.01），八个SNP中的五个有资格进行分析。我们使用了全面的基于体素的形态计量学（VBM）技术来研究这五个SNP对日本患有日本患者的大股票纯合子和小方便载体之间的GM体积的影响schizophrenia(n?=?173) and healthy subjects (n?=?449). The rs7914558 risk variant atCNNM2was associated with voxel-based GM volumes in the bilateral inferior frontal gyri (right T?=?4.96, p?=?0.0088, left T?=?4.66, p?=?0.031). These peak voxels, which were affected by the variant, existed in the orbital region of the inferior frontal gyri. Individuals with the risk G/G genotype of rs7914558 had smaller GM volumes in the bilateral inferior frontal gyri than carriers of the non-risk A-allele. Although several effects of the genotype and the genotype-diagnosis interaction of other SNPs on GM volumes were observed in the exploratory VBM analyses, these effects did not remain after the FWE-correction for multiple tests (p?>?0.05). Our findings suggest that the genetic variant in theCNNM2gene could be implicated in the pathogenesis ofschizophrenia通过轨道下部回旋中轨道区域的GM体积脆弱性。 |
| SCZ关键字 | schizophrenia |
| 2 | JAMA Psychiatry 2013 Jun 70: 573-81 |
| PMID | 23894747 |
| Title | A comprehensive family-based replication study of schizophrenia genes. |
| Abstract | schizophrenia(SCZ) is a devastating psychiatric condition. Identifying the specific genetic variants and pathways that increase susceptibility to SCZ is critical to improve disease understanding and address the urgent need for new drug targets. To identify SCZ susceptibility genes. We integrated results from a meta-analysis of 18 genome-wide association studies (GWAS) involving 1,085,772 single-nucleotide polymorphisms (SNPs) and 6 databases that showed significant informativeness for SCZ. The 9380 most promising SNPs were then specifically genotyped in an independent family-based replication study that, after quality control, consisted of 8107 SNPs. Linkage meta-analysis, brain transcriptome meta-analysis, candidate gene database, OMIM, relevant mouse studies, and expression quantitative trait locus databases. 我们包括来自6个数据库的11,185例病例和10,768名对照受试者，在质量控制后，有6298个个人（包括3286例）来自1811年的核家庭。 Case-control status for SCZ. Replication results showed a highly significant enrichment of SNPs with small P values. Of the SNPs with replication values of P.01, the proportion of SNPs that had the same direction of effects as in the GWAS meta-analysis was 89% in the combined ancestry group (sign test, P < 2.20 x 10(-16) and 93% in subjects of European ancestry only (P < 2.20 < 10(-16)). Our results supported the major histocompatibility complex region showing a3.7-fold overall enrichment of replication values of P < .01 in subjects from European ancestry. We replicated SNPs in TCF4 (P = 2.53 x 10(-10)) and NOTCH4 (P = 3.16 x 10(-7)) that are among the most robust SCZ findings. More novel findings included POM121L2 (P = 3.51 x 10(-7)), AS3MT (P = 9.01 x 10(-7)),CNNM2(P = 6.07 = 10(-7)), and NT5C2(P = 4.09 x 10(-7)). To explore the many small effects, we performed pathway analyses. The most significant pathways involved neuronal function (axonal guidance, neuronal systems, and L1 cell adhesion molecule interaction)and the immune system (antigen processing, cell adhesion molecules relevant to T cells, and translocation to immunological synapse). We replicated novel SCZ disease genes and pathogenic pathways. Better understanding the molecular and biological mechanisms involved withschizophreniamay improve disease management and may identify new drug targets. |
| SCZ关键字 | schizophrenia |
| 3 | Front Neurosci 2014 -1 8: 331 |
| PMID | 25414627 |
| Title | Neuroinformatic共同和不同的通用的分析netic components associated with major neuropsychiatric disorders. |
| 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), andschizophrenia(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和ZnRD1。使用一套神经信息学资源，我们表明许多共享基因与突触后密度（PSD）有关，在免疫组织中表达，并在发育中的人脑中共表达。使用翻译跨物种方法，我们检测到了六个疾病中的每一个共享的两个不同的遗传成分。第一部分参与了CNS发育，神经投影和突触传播，而第二部分则与各种细胞质细胞器和细胞过程有关。这些遗传成分合并占遗传负荷的20-30％。剩余的风险由独特的特定于疾病的变体赋予。我们对共享和独特遗传因素的系统比较分析突出了关键基因集和分子过程，这些基因集和分子过程最终可能会改善这些衰弱的疾病的诊断和治疗。 |
| SCZ关键字 | schizophrenia |
| 4 | Br J Psychiatry 2014 Feb 204: 115-21 |
| PMID | 24311551 |
| Title | Effects of a novel schizophrenia risk variant rs7914558 at CNNM2 on brain structure and attributional style. |
| Abstract | A single nucleotide polymorphism (rs7914558) within the cyclin M2 (CNNM2）基因最近被确定为常见的风险变体schizophrenia. The mechanism by whichCNNM2confers risk is unknown. To determine the impact of the rs7914558 risk 'G' allele [corrected] on measures of neurocognition, social cognition and brain structure. Patients withschizophrenia(n = 400) and healthy controls (n = 160) completed measures of neuropsychological function and social cognition. Structural magnetic resonance imaging data were also acquired from an overlapping sample of Irish healthy controls (n = 159) and an independent sample of Italian patients (n = 82) and healthy controls (n = 39). No effects of genotype on neuropsychological test performance were observed. However, a dosage effect of the risk allele was found for an index of social cognition (i.e. attributional style), such that risk status was associated with reduced self-serving bias across groups (GG>AG>AA, P<0.05). Using voxel-based morphometry to investigate neuroanatomical regions putatively supporting social cognition, risk carriers had relatively increased grey matter volume in the right temporal pole and right anterior cingulate cortex (Pcorrected<0.05) in the Irish healthy controls sample; neuroanatomical associations betweenCNNM2and grey matter volume in anterior cingulate cortex were also observed in the Italianschizophreniaand healthy controls samples. Although the biological role ofCNNM2inschizophreniaremains unknown, these data suggest that thisCNNM2risk variant rs7914558 may have an impact on neural systems relevant to social cognition. How such effects may mediate the relationship between genotype and disease risk remains to be established. |
| SCZ关键字 | schizophrenia |
| 5 | Psychiatry Res 2015 Dec 230: 964-7 |
| PMID | 26596365 |
| Title | Association of age-of-onset groups with GWAS significant schizophrenia and bipolar disorder loci in Romanian bipolar I patients. |
| Abstract | We investigated the influence of the age-of-onset (AO) on the association of 45 loci conferring risk for bipolar disorder (BP) andschizophreniawith BP-type-I in a Romanian sample (461 patients, 436 controls). The AO-analysis implicated the EGFR gene, as well as loci in other genes, in the AO variation of BP-type-I and revealed for the first time the link between BP-type-I and risk variants considered specific toschizophrenia(polymorphisms in MMP16/RIPK2 andCNNM2genes). |
| SCZ关键字 | schizophrenia |
| 6 | BR J Psychiatry 2015 Apr 206：343-4 |
| PMID | 25833874 |
| Title | Influences of schizophrenia risk variant rs7914558 at CNNM2 on brain structure. |
| Abstract | -1 |
| SCZ关键字 | schizophrenia |
| 7 | 点。j .地中海,麝猫。B Neuropsychiatr。麝猫。2016ar -1: -1 |
| PMID | 27004590 |
| Title | Genome-wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis-regulation of BORCS7, AS3MT, and NT5C2 in the human brain. |
| Abstract | Chromosome 10q24.32-q24.33 is one of the most robustly supported risk loci to emerge from genome-wide association studies (GWAS) ofschizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele-specific expression to assess cis-regulatory effects associated with the two best-supportedschizophreniarisk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT,CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis-effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility toschizophreniaarising from genetic variation at the chromosome 10q24 locus. � 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. |
| SCZ关键字 | schizophrenia |