The<i>CHRM3</i>gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia

Wang, Qinyu; Cheng, Wei; Li, M.; Ren, Hongyan; Hu, Xun; Deng, Wei; Ma, Xiaoyan; Zhao, Liansheng; Wang, Y.; Xiang, Bo; Wu, Hua; Sham, Pak C.; Feng, Jianfeng; Li, T.

doi:10.1017/s0033291716000167

Cited by 19 publications

(16 citation statements)

References 54 publications

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“…Furthermore, it was assumed that the effect of genetics on functional networks between healthy people and their siblings was insignificant. Some recent studies have found an effect of genetics on functional networks between schizophrenia and their sibling [50]. Third, every schizophrenic subject was taking antipsychotic medication at the time of the diagnostic test.…”

Section: Discussionmentioning

confidence: 99%

Differences Between Schizophrenic and Normal Subjects Using Network Properties from fMRI

et al. 2017

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Schizophrenia has been proposed to result from impairment of functional connectivity. We aimed to use machine learning to distinguish schizophrenic subjects from normal controls using a publicly available functional MRI (fMRI) data set. Global and local parameters of functional connectivity were extracted for classification. We found decreased global and local network connectivity in subjects with schizophrenia, particularly in the anterior right cingulate cortex, the superior right temporal region, and the inferior left parietal region as compared to healthy subjects. Using support vector machine and 10-fold cross-validation, nine features reached 92.1% prediction accuracy, respectively. Our results suggest that there are significant differences between control and schizophrenic subjects based on regional brain activity detected with fMRI.

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Section: Discussionmentioning

confidence: 99%

Differences Between Schizophrenic and Normal Subjects Using Network Properties from fMRI

et al. 2017

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“…As for the CHRM3 gene, which is a cholinergic receptor and is related to schizophrenia, it may be a potential therapeutic target for COPD patients (30,31). And we found six antipsychotic drugs targeting CHRM3.…”

Section: Discussionmentioning

confidence: 86%

Comprehensive Analysis Reveals A Six-Gene Signature and Associated Drugs in Alzheimer Disease

Jiang¹,

Tan²,

Wang³

2020

Preprint

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Background: Alzheimer disease (AD) is a progressive neurodegenerative disease caused by many factors. The essential genes and signaling pathways involved in the pathogenesis of AD are still unknown. The purpose of our research is to analyze and screen out potential molecular biomarkers and related signaling pathways.Methods: We obtained the gene expression profile of GSE18309 from the gene expression Omnibus website. Then, we used the Limma package in Rstudio to screen out differentially expressed genes (DEGs), followed by the corresponding cell signal pathway enrichment using DAVID analysis. Finally, STRING used to obtain the protein-protein interaction (PPI) network and the corresponding hub gene obtained through MCODE of Cytoscape software.Results: The results showed that a total of 119 upregulated genes and 160 downregulated genes were identified, which met the criteria of |log2 changes| ≥2, adjusted P value <0.01. Through the PPI network, the hub gene module we obtained shows that genes such as GNG13, EDNRB, CHRM3, CCKAR, FFAR4 and TRIO are closely related to AD. The signaling pathway is about signal transducer activity, G-protein coupled receptor activity and transmembrane signaling receptor activity. Conclusions: In summary, the above-obtained hub gene and the identified signaling pathway will help explore the pathogenesis of AD; and provide new therapeutic targets and prognostic assessment for AD.

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“…The genotype data has been used by our previous studies and the details of genotyping and quality control have been published elsewhere 14 , 15 . In brief, DNA extracted from whole blood sample was genotyped using HumanOmniZhongHua-8 BeadChip (Illumina, San Diego, CA) and the raw genotype data underwent systematic quality control steps (QCs) including missing rate per genotype (< 5%) and per individuals (< 3%), minor allele frequency (MAF, < 0.01), Hardy-Weinberg equilibrium tests ( p < 0.001), cryptic relatedness and heterozygosity rate.…”

Section: Methodsmentioning

confidence: 99%

“…Wang et al . later used functional connectivity as the QTs in GWAS of schizophrenia and found that the CHRM3 gene was significantly associated with functional connectivity deficits in schizophrenia 15 . These studies highlighted the efficacy of QTs as the endophenotype in exploring the pathogenesis of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia

Ren

Wang

Lei

et al. 2017

Sci Rep

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Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10−8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10−7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10−17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.

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TheCHRM3gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia

Cited by 19 publications

References 54 publications

Differences Between Schizophrenic and Normal Subjects Using Network Properties from fMRI

Differences Between Schizophrenic and Normal Subjects Using Network Properties from fMRI

Comprehensive Analysis Reveals A Six-Gene Signature and Associated Drugs in Alzheimer Disease

The common variants implicated in microstructural abnormality of first episode and drug-naïve patients with schizophrenia

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