A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia

Pérez-Santiago, Josué; Dı́ez-Alarcia, Rebeca; Callado, Luís F.; Zhang, Jin X.; Chana, Gursharan; White, Cory H.; Glatt, Stephen J.; Tsuang, Ming T.; Everall, Ian; Meana, J. Javier; Woelk, Christopher H.

doi:10.1016/j.jpsychires.2012.08.005

Cited by 71 publications

(72 citation statements)

References 44 publications

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“…3. The differential expression gene set are based on previous studies (GLATT et al 2005;MAYCOX et al 2009;PEREZ-SANTIAGO et al 2012;FILLMAN et al 2013;GARDINER et al 2013;HWANG et al 2013;SAINZ et al 2013;SANDERS et al 2013;SELLMANN et al 2014). Figure 5) and the expression values of a training gene across the same combinations of brain regions and time stages.…”

Section: Supplementary Figuresmentioning

confidence: 99%

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

Lin¹,

Cai²,

Zhang³

et al. 2016

Genetics

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Schizophrenia is a severe mental disorder with a large genetic component. Recent genome-wide association studies (GWAS) have identified many schizophrenia-associated common variants. For most of the reported associations, however, the underlying biological mechanisms are not clear. The critical first step for their elucidation is to identify the most likely disease genes as the source of the association signals. Here, we describe a general computational framework of post-GWAS analysis for complex disease gene prioritization. We identify 132 putative schizophrenia risk genes in 76 risk regions spanning 120 schizophrenia-associated common variants, 78 of which have not been recognized as schizophrenia disease genes by previous GWAS. Even more significantly, 29 of them are outside the risk regions, likely under regulation of transcriptional regulatory elements contained therein. These putative schizophrenia risk genes are transcriptionally active in both brain and the immune system, and highly enriched among cellular pathways, consistent with leading pathophysiological hypotheses about the pathogenesis of schizophrenia. With their involvement in distinct biological processes, these putative schizophrenia risk genes, with different association strengths, show distinctive temporal expression patterns, and play specific biological roles during brain development.

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Section: Supplementary Figuresmentioning

confidence: 99%

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

Lin¹,

Cai²,

Zhang³

et al. 2016

Genetics

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show abstract

“…In fact, the high throughput transcriptome profiling experiments conducted with DNA microarrays identified several molecular processes in SCZ such as myelination, synaptic transmission, metabolism, ubiquitination and immune function (Kumarasinghe et al, 2012;Mistry et al, 2013b). Historically, as for all investigated psychiatric diseases, postmortem brain samples have been considered as the gold standard material to profile SCZ (Arion et al, 2007;Barnes et al, 2011;Chen et al, 2013;Hagihara et al, 2014;Mistry et al, 2013a,b;Perez-Santiago et al, 2012;Saetre et al, 2007;Schmitt et al, 2011;Torkamani et al, 2010). However, such tissue presents many limitations including access and collection of large sample sizes, tissue preparation and conservation, and antemortem diagnosis.…”

Section: Introductionmentioning

confidence: 99%

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

Bergon

Belzeaux

Comte

et al. 2015

Schizophrenia Research

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The molecular mechanisms underlying schizophrenia remain largely unknown. Although schizophrenia is a mental disorder, there is increasing evidence to indicate that inflammatory processes driven by diverse environmental factors play a significant role in its development. With gene expression studies having been conducted across a variety of sample types, e.g., blood and postmortem brain, it is possible to investigate convergent signatures that may reveal interactions between the immune and nervous systems in schizophrenia pathophysiology. We conducted two meta-analyses of schizophrenia microarray gene expression data (N=474) and non-psychiatric control (N=485) data from postmortem brain and blood. Then, we assessed whether significantly dysregulated genes in schizophrenia could be shared between blood and brain. To validate our findings, we selected a top gene candidate and analyzed its expression by RT-qPCR in a cohort of schizophrenia subjects stabilized by atypical antipsychotic monotherapy (N=29) and matched controls (N=31). Meta-analyses highlighted inflammation as the major biological process associated with schizophrenia and that the chemokine receptor CX3CR1 was significantly down-regulated in schizophrenia. This differential expression was also confirmed in our validation cohort. Given both the recent data demonstrating selective CX3CR1 expression in subsets of neuroimmune cells, as well as behavioral and neuropathological observations of CX3CR1 deficiency in mouse models, our results of reduced CX3CR1 expression adds further support for a role played by monocyte/microglia in the neurodevelopment of schizophrenia.

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“…The products of this activation are C4b, an opsonin that binds covalently to the complement activating target. Some evidence has indicated that dysfunction of C4b may be involved in the alterations of the innate and adaptive immune systems in schizophrenia [10,14].…”

Section: Introductionmentioning

confidence: 99%

An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia

Wang

Lu²,

et al. 2015

Neuroscience Letters

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A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia

Cited by 71 publications

References 44 publications

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

Integrated Post-GWAS Analysis Sheds New Light on the Disease Mechanisms of Schizophrenia

CX3CR1 is dysregulated in blood and brain from schizophrenia patients

An evaluation of association between common variants in C4BPB/C4BPA genes and schizophrenia

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