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首页> 外文期刊>Neuron >Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia
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Novel Findings from CNVs Implicate Inhibitory and Excitatory Signaling Complexes in Schizophrenia

机译：从CNV的新发现暗示精神分裂症的抑制性和兴奋性信号复合物

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We sought to obtain novel insights into schizophrenia pathogenesis by exploiting the association between the disorder and chromosomal copy number (CNV) burden. We combined data from 5,745 cases and 10,675 controls with other published datasets containing genome-wide CNV data. In this much-enlarged sample of 11,355 cases and 16,416 controls, we show for the first time that case CNVs are enriched for genes involved in GABAergic neuro-transmission. Consistent with non-genetic reports of GABAergic deficits in schizophrenia, our findings now show disrupted GABAergic signaling is of direct causal relevance, rather than a secondary effect or due to confounding. Additionally, we independently replicate and greatly extend previous findings of CNV enrichment among genes involved in glutamatergic signaling. Given the strong functional links between the major inhibitory GABAergic and excitatory glutamatergic systems, our findings converge on a broad, coherent set of pathogenic processes, providing firm foundations for studies aimed at dissecting disease mechanisms.
机译：我们试图通过利用疾病与染色体拷贝数（CNV）负担之间的关联来获得对精神分裂症发病机理的新颖见解。我们将来自5,745例病例和10,675例对照的数据与包含基因组范围CNV数据的其他已发布数据集进行了合并。在这个11,355例病例和16,416例对照的大量样本中，我们首次显示出CNV富含与GABA能神经传递有关的基因。与精神分裂症中GABA能缺陷的非遗传性报道一致，我们的发现现在表明，破坏的GABA能信号是直接因果相关的，而不是次要作用或由于混淆。此外，我们独立复制并大大扩展了涉及谷氨酸能信号传导的基因之间CNV富集的先前发现。鉴于主要的抑制性GABA能系统和兴奋性谷氨酸能系统之间的强大功能联系，我们的发现集中在广泛而连贯的致病过程上，为旨在研究疾病机制的研究奠定了坚实的基础。

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