UCL Genetics Institute, University College London, UK; Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, UK.
UCL Genetics Institute, University College London, UK; The Francis Crick Institute, UK; Department of Molecular Neuroscience, UCL Institute of Neurology, UK.
Schizophr Res. 2018 Jul;197:346-348. doi: 10.1016/j.schres.2017.11.018. Epub 2017 Nov 20.
There is strong cumulative evidence for the involvement of miR-137 and its targets in the aetiology of schizophrenia. Here we test whether variants, especially rare variants, in miR-137 binding sites are associated with schizophrenia in an exome-sequenced sample of 4225 cases and 5834 controls. Only a small proportion of binding sites were covered by the capture system which had been used. A weighted burden test using the 372 detected variants demonstrated an excess among cases significant at p=0.024. The sample size is too small to implicate individual variants or genes but overall this finding does provide some further support for the hypothesis that disruption of miR-137 binding sites can increase the risk of schizophrenia, perhaps by leading to over-expression of the target gene. We recommend that future exome sequencing studies should cover the untranscribed regions of genes, which contain the microRNA binding sites, in order that this potentially important pathogenic mechanism can be adequately investigated.
miR-137 及其靶基因在精神分裂症发病机制中具有重要作用。本研究在经外显子组测序的 4225 例病例和 5834 例对照中，检测 miR-137 结合位点的变异，尤其是罕见变异，是否与精神分裂症相关。该捕获系统仅覆盖了一小部分结合位点。利用检测到的 372 个变异进行加权负担测试，结果显示病例组显著富集（p=0.024）。由于样本量太小，无法确定单个变异或基因，但总体而言，这一发现为 miR-137 结合位点的破坏可能会增加精神分裂症风险的假说提供了一些额外的支持，其机制可能是导致靶基因过表达。我们建议未来的外显子组测序研究应涵盖基因的非转录区域，因为这些区域包含 microRNA 结合位点，以便充分研究这一潜在重要的致病机制。
