| 1 | Psychiatry Clin. Neurosci. 2013 May 67: 277-9 |
|---|---|
| PMID | 23683160 |
| Title | Resequencing and association analysis of MIR137 with schizophrenia in a Japanese population. |
| Abstract | MicroRNA may play a role in the pathophysiology ofschizophrenia. A recent meta-analysis of genome-wide association studies indicated a significant association betweenschizophreniaand a common intronic variation inMIR137HG(microRNA 137 host gene) encoding the primary microRNA-137. To explore additional risk variations forschizophrenia, we resequenced MIR137 and performed an association analysis in 1321 Japanese individuals. By resequencing, we detected four sequence variations in the 5' and 3' flanking regions. There were no significant associations between these variations andschizophrenia. Our resequencing and association analysis of MIR137 failed to find additional risk variations forschizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | Neurosci. Lett. 2015 Aug 602: 44-9 |
| PMID | 26123324 |
| Title | MIR137HG risk variant rs1625579 genotype is related to corpus callosum volume in schizophrenia. |
| Abstract | Genome-wide association studies implicate theMIR137HGrisk variant rs1625579 (MIR137HG房车)在宿主基因微rna - 137罐ential regulator ofschizophreniasusceptibility. We examined the influence ofMIR137HGrv genotype on 17 subcortical and callosal volumes in a large sample of individuals withschizophreniaand healthy controls (n=841). Although the volumes were overall reduced relative to healthy controls, for individuals withschizophreniathe homozygousMIR137HGrv risk genotype was associated with attenuated reduction of mid-posterior corpus callosum volume (p=0.001), along with trend-level effects in the adjacent central and posterior corpus callosum. These findings are unique in the literature and remain robust after analysis in ethnically homogenous and single-scanner subsets of the larger sample. Thus, our study suggests that the mechanisms wherebyMIR137HGrv works to increaseschizophreniarisk are not those that generate the corpus callosum volume reductions commonly found in the disorder. |
| SCZ Keywords | schizophrenia |
| 3 | J Neural Transm (Vienna) 2015 Jan 122: 79-97 |
| PMID | 25395183 |
| Title | Heterogeneity and individuality: microRNAs in mental disorders. |
| Abstract | MicroRNAs are about 22 nucleotide long single-stranded RNA molecules, negatively regulating gene expression of a single gene or a gene network. In neural tissues, they have been implicated in developmental and neuroplasticity-related processes, such as neurogenesis, differentiation, apoptosis and long-term potentiation. Their molecular mode of action is reminiscent of findings of genome-wide association studies in mental disorders, unable to attribute the risk of disease to a specific gene, but rather to multiple genes, gene-networks and gene-environment interaction. As such, microRNAs are an attractive target for research. Here, we review clinical studies conducted in humans on microRNAs in mental disorders with a particular focus onschizophrenia, bipolar disorder, major depressive disorder and anxiety disorders. The majority of clinical studies have focused onschizophrenia. The most robust finding has been reported for rs1625579 located inMIR137HG, which was associated withschizophreniaon a genome-wide level. Concerning bipolar disorder, major depression and anxiety disorders, promising results have been published, but only a considerably smaller number of clinical studies is available and genome-wide association studies did not suggest a direct link to microRNAs so far. Expression of microRNAs as biomarkers of mental disorders and treatment response is currently emerging with preliminary results. Larger-scaled genetic and functional studies along with translational research are needed to enhance our understanding of microRNAs in mental disorders. These studies will aid in disentangling the complex genetic nature of these disorders and possibly contribute to the development of novel, individualized diagnostic and therapeutic approaches. |
| SCZ Keywords | schizophrenia |
| 4 | Transl Psychiatry 2016 -1 6: e724 |
| PMID | 26836412 |
| Title | Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia. |
| Abstract | Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis ofschizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of aMIR137HGrisk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessingschizophreniarisk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these fourschizophreniarisk-associated genes in 221 Caucasian subjects (89schizophreniapatients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found thatschizophreniasubjects homozygous for theMIR137HGrisk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with theMIR137HGrisk variant may influence GMC inschizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease. |
| SCZ Keywords | schizophrenia |