| 1 | 精神病学摩尔。2011年3月16日:321 - 32 |
|---|---|
| PMID | 20195266 |
| Title | Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. |
| Abstract | Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment ofschizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738schizophreniapatients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study. Outcomes included 12 indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. A total of 21 SNPs satisfied this criterion. The top finding indicated that a SNP in Meis homeobox 2 (MEIS2) mediated the effects of risperidone on hip circumference (q=0.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q=0.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2,SOX5和ATF7IP2, as well as in several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement, and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication. |
| SCZ Keywords | schizophrenia |
| 2 | PLoS ONE 2013 -1 8: e53042 |
| PMID | 23301017 |
| Title | Discovery, validation and characterization of Erbb4 and Nrg1 haplotypes using data from three genome-wide association studies of schizophrenia. |
| Abstract | schizophreniais one of the most common and complex neuropsychiatric disorders, which is contributed both by genetic and environmental exposures. Recently, it is shown that NRG1-mediated ErbB4 signalling regulates many important cellular and molecular processes such as cellular growth, differentiation and death, particularly in myelin-producing cells, glia and neurons. Recent association studies have revealed genomic regions of NRG1 and ERBB4, which are significantly associated with risk of developingschizophrenia; however, inconsistencies exist in terms of validation of findings between distinct populations. In this study, we aim to validate the previously identified regions and to discover novel haplotypes of NRG1 and ERBB4 using logistic regression models and Haploview analyses in three independent datasets from GWAS conducted on European subjects, namely, CATIE, GAIN and nonGAIN. We identified a significant 6-kb block in ERBB4 between chromosome locations 212,156,823 and 212,162,848 in CATIE and GAIN datasets (p = 0.0206 and 0.0095, respectively). In NRG1, a significant 25-kb block, between 32,291,552 and 32,317,192, was associated with risk ofschizophreniain all CATIE, GAIN, and nonGAIN datasets (p = 0.0005, 0.0589, and 0.0143, respectively). Fine mapping and FastSNP analysis of genetic variation located within significantly associated regions proved the presence of binding sites for several transcription factors such as SRY,SOX5，CEPB和ETS1。在这项研究中，我们在三个独立的欧洲人群中发现并验证了ERBB4和NRG1的单倍型。这些发现表明，这些单倍型在发展中起着重要作用schizophreniaby affecting transcription factor binding affinity. |
| SCZ Keywords | schizophrenia |
| 3 | Eur Arch Psychiatry Clin Neurosci 2014 Jun 264: 297-309 |
| PMID | 24287731 |
| Title | Gene expression in superior temporal cortex of schizophrenia patients. |
| Abstract | We investigated gene expression pattern obtained from microarray data of 10schizophrenia患者和10名对照受试者。术后获得脑组织样品；因此，死亡时患者的不同年龄也允许研究多年来表达模式的动态行为。我们使用统计检验和降低降低方法来表征两组中差异表达的基因的子集。一组10个基因被显着下调，并在该基因中上调了一组较大的40个基因schizophreniapatients. Interestingly, the set of upregulated genes includes a large number of genes associated with gene transcription (zinc finger proteins and histone methylation) and apoptosis. We furthermore identified genes with a significant trend correlating with age in the control (MLL3) or theschizophreniagroup (SOX5, CTRL). Assessments of correlations of other genes with the disorder (RRM1) or with the duration of medication could not be resolved, because all patients were medicated. This hypothesis-free approach uncovered a series of genes differentially expressed inschizophreniathat belong to a number of distinct cell functions, such as apoptosis, transcriptional regulation, cell motility, energy metabolism and hypoxia. |
| SCZ Keywords | schizophrenia |