caudate nucleus

尾状核
  • 文章类型: Journal Article
    精神分裂症是一种神经发育性脑部疾病,其遗传风险与整个生命周期中临床现象的转变有关。我们调查了推定的精神分裂症风险基因在死后人类前额叶皮层(DLPFC)的大脑共表达网络中的收敛性,海马体,尾状核,和齿状回颗粒细胞,按特定年龄解析(总N=833)。结果支持早期前额叶参与精神分裂症的生物学基础,并揭示了区域的动态相互作用,与将所有年龄段合并在一起相比,年龄解析解释了精神分裂症风险的更多差异。跨多个数据源和出版物,我们确定了28个基因,这些基因是DLPFC中精神分裂症风险基因富集模块中最一致发现的伴侣;23个是以前未发现的与精神分裂症的关联.在iPSC衍生的神经元中,这些基因与精神分裂症风险基因的关系得以维持。精神分裂症的遗传结构嵌入在大脑区域和时间之间不断变化的共表达模式中,可能承保其不断变化的临床表现。
    Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and dentate gyrus granule cells, parsed by specific age periods (total N = 833). The results support an early prefrontal involvement in the biology underlying schizophrenia and reveal a dynamic interplay of regions in which age parsing explains more variance in schizophrenia risk compared to lumping all age periods together. Across multiple data sources and publications, we identify 28 genes that are the most consistently found partners in modules enriched for schizophrenia risk genes in DLPFC; twenty-three are previously unidentified associations with schizophrenia. In iPSC-derived neurons, the relationship of these genes with schizophrenia risk genes is maintained. The genetic architecture of schizophrenia is embedded in shifting coexpression patterns across brain regions and time, potentially underwriting its shifting clinical presentation.
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