RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia.
RNA-Seq analysis implicates dysregulation of the immune system in schizophrenia.
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DOI：
10.1186/1471-2164-13-s8-s2
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发表时间：
2012
期刊：
影响因子：
4.4
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Xu J;Sun J;Chen J;Wang L;Li A;Helm M;Dubovsky SL;Bacanu SA;Zhao Z;Chen X
虽然全基因组关联研究确定了一些有希望的精神分裂症候选基因，但大多数风险基因仍然未知。我们感兴趣的是测试整合基因表达和其他功能信息是否可以促进易感基因和相关生物学途径的鉴定。我们进行了高通量测序分析，以评估从3名精神分裂症患者和3名健康对照的血液样品中分离的mRNA表达。我们还对10名精神分裂症患者和匹配的对照进行了合并测序。差异表达基因的鉴定采用t检验。在单独测序的数据集中，我们确定了198个病例和对照之间差异表达的基因，其中19个已通过合并测序数据集验证，21个在全基因组关联数据集的基于基因的关联分析中达到标称显著性。对这些差异表达基因的通路分析表明，它们在免疫相关通路中高度富集。两个基因，S100A8和TYROBP，在个体和合并的测序数据集中表达变化一致，在基于基因的关联分析中名义上是显著的。整合基因表达和通路分析与全基因组关联可能是一种有效的方法来确定精神分裂症的风险基因。
While genome-wide association studies identified some promising candidates for schizophrenia, the majority of risk genes remained unknown. We were interested in testing whether integration gene expression and other functional information could facilitate the identification of susceptibility genes and related biological pathways. We conducted high throughput sequencing analyses to evaluate mRNA expression in blood samples isolated from 3 schizophrenia patients and 3 healthy controls. We also conducted pooled sequencing of 10 schizophrenic patients and matched controls. Differentially expressed genes were identified by t-test. In the individually sequenced dataset, we identified 198 genes differentially expressed between cases and controls, of them 19 had been verified by the pooled sequencing dataset and 21 reached nominal significance in gene-based association analyses of a genome wide association dataset. Pathway analysis of these differentially expressed genes revealed that they were highly enriched in the immune related pathways. Two genes, S100A8 and TYROBP, had consistent changes in expression in both individual and pooled sequencing datasets and were nominally significant in gene-based association analysis. Integration of gene expression and pathway analyses with genome-wide association may be an efficient approach to identify risk genes for schizophrenia.