What genes are differentially expressed in individuals with schizophrenia? A systematic review.
What genes are differentially expressed in individuals with schizophrenia? A systematic review.
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DOI：
10.1038/s41380-021-01420-7
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发表时间：
2022-03
影响因子：
11
通讯作者：
Almasy, Laura
中科院分区：
文献类型：
--
作者：
Merikangas, Alison K.;Shelly, Matthew;Knighton, Alexys;Kotler, Nicholas;Tanenbaum, Nicole;Almasy, Laura
精神分裂症是一种严重、复杂的精神障碍，其特征是阳性症状、阴性症状和认知功能受损的组合。精神分裂症具有高度遗传性（~80%），具有多因素病因和复杂的多基因遗传结构。尽管有大量的遗传变异与精神分裂症有关，但很少有因果变异被确定。深入了解这些遗传变异的机制影响可能有助于我们将这些发现应用于预防和治疗。尽管在过去的15年里，有300多项关于精神分裂症基因表达的研究，但没有一项研究得出了与精神分裂症风险有关的特定基因的一致证据。这项工作的目的是进行一个系统的审查和精神分裂症全基因组基因表达的病例对照研究的综合。在PubMed，EmBase和Web of Science中完成了全面的文献检索，并在对研究进行系统性综述后，从符合以下纳入标准的研究中提取了数据：人类病例对照研究，比较了2000年1月1日至2020年6月30日期间发表的诊断为精神分裂症的个体与健康对照的全基因组转录组。从这些研究中提取病例中差异表达的基因，并将重叠基因与以前的全基因组关联、结构变异和组织表达研究的研究结果进行比较。全转录组分析确定了与以前报道的精神分裂症全基因组关联、外显子组测序和结构变异研究不同的基因。只有一个基因，GBP 2，在五项研究中被复制。先前的研究表明，该基因可能在精神分裂症病因学中的免疫功能中发挥作用，这反过来可能对风险分析，预防和治疗产生影响。这篇综述强调了阻碍有效的荟萃分析和跨研究综合的方法学不一致。协变量、基因命名和报告结果方法的标准化可以增强我们对基因对精神分裂症病因学产生影响的潜在机制的理解。虽然这些结果是有希望的，协调方法的协作努力将有助于确定精神分裂症的基因基础的作用。
Schizophrenia is a severe, complex mental disorder characterized by a combination of positive symptoms, negative symptoms, and impaired cognitive function. Schizophrenia is highly heritable (~80%) with multifactorial etiology and complex polygenic genetic architecture. Despite the large number of genetic variants associated with schizophrenia, few causal variants have been established. Gaining insight into the mechanistic influences of these genetic variants may facilitate our ability to apply these findings to prevention and treatment. Though there have been more than 300 studies of gene expression in schizophrenia over the past 15 years, none of the studies have yielded consistent evidence for specific genes that contribute to schizophrenia risk. The aim of this work is to conduct a systematic review and synthesis of case–control studies of genome-wide gene expression in schizophrenia. Comprehensive literature searches were completed in PubMed, EmBase, and Web of Science, and after a systematic review of the studies, data were extracted from those that met the following inclusion criteria: human case–control studies comparing the genome-wide transcriptome of individuals diagnosed with schizophrenia to healthy controls published between January 1, 2000 and June 30, 2020 in the English language. Genes differentially expressed in cases were extracted from these studies, and overlapping genes were compared to previous research findings from the genome-wide association, structural variation, and tissue-expression studies. The transcriptome-wide analysis identified different genes than those previously reported in genome-wide association, exome sequencing, and structural variation studies of schizophrenia. Only one gene, GBP2, was replicated in five studies. Previous work has shown that this gene may play a role in immune function in the etiology of schizophrenia, which in turn could have implications for risk profiling, prevention, and treatment. This review highlights the methodological inconsistencies that impede valid meta-analyses and synthesis across studies. Standardization of the use of covariates, gene nomenclature, and methods for reporting results could enhance our understanding of the potential mechanisms through which genes exert their influence on the etiology of schizophrenia. Although these results are promising, collaborative efforts with harmonization of methodology will facilitate the identification of the role of genes underlying schizophrenia.
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作者：
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作者：
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DOI：
10.1002/ajmg.b.31006
发表时间：
2010-03-05
影响因子：
2.8
作者：
Bousman, Chad A.;Chana, Gursharan;Glatt, Stephen J.;Chandler, Sharon D.;Lucero, Ginger R.;Tatro, Erick;May, Todd;Lohr, James B.;Kremen, William S.;Tsuang, Ming T.;Everall, Ian P.
通讯作者：
Everall, Ian P.