Based On Protein Interactions For Schizophrenia And Obsessive-compulsive Disorder Related Inheritance Risk Gene Data Mining And Analysis

Objective To make a comprehensive analysis of genetic risk genes of schizophrenia with miRNA gene data set,and explore the regulatory network and mechanism of miRNA in schizophrenia.Methods Schizophrenia-associated genetic loci profiles were derived from a genome-wide association study(GWAS)from the Schizophrenia Working Group of the Psychiatric Genomics Consortium(PGC)dataset.Experimentally confirmed miRNAs and their target genes were retrieved from a miRTarBase.Multi-marker Analysis of GenoMic Annotation(MAGMA)was used to analyze the genes targeted regulated by competitive gene set miRNA.The functional pathway analysis and literature verification of target genes were performed by Pathway Studio.The association between GWAS of antipsychotic drugs and target genes was used to further validate the relevant therapeutic response.Results Three new risk factors of schizophrenia,namely miR-208b-3p,miR-208a-3p,miR-494-5p and their targets in calcium voltage gated channel subunit α 1c(CACNA1C)and BCL2 were found to further confirm the genetic risk factors of schizophrenia.Protein interaction network analysis showed that both miR-208a-3p and miR-208b-3p decreased the expression of RNA binding protein(QKI)and promoted neuronal demyelination and ischemia-reperfusion injury,as well as myocardial fibrosis and cardiomyocyte apoptosis.In addition,both QKI and hsa-miR-494-5p were involved in the inhibition of glioma.Conclusion The study results showed that miRNAs was the basis of the pathophysiological co-regulatory network of schizophrenia,and the participation of miR-208a-3p in schizophrenia and cardiovascular co-regulatory network may be the pathological basis of high cardiovascular mortality in schizophrenia.As a tumor inhibitor,miR-494-5p further suggest the biological basis of low incidence of brain tumors in patients with schizophrenia.Objective:To investigate the risk indicators of cerebral infarction in schizophrenia by studying the expression of miR-33a and miR-494a in schizophrenia complicated with cerebral infarction and detecting lipid metabolism-related indicators.Methods:Collect data from patients with schizophrenia complicated with cerebral infarction,simple schizophrenia,and normal group.A total of 26 subjectss of data were collected in each group.The blood of all subjects was collected,and the data of triglyceride,total cholesterol,Data of low-density lipoprotein and high-density lipoprotein,and RT-PCR analysis of miR-33a and miR-494a gene expression levels in patients,while using receiver characteristic curve(ROC)to analyze its effects on diagnostic in schizophrenia with cerebral infarction patient’sResults:1.The levels of total cholesterol and triglycerides in the schizophrenia combined with cerebral infarction group were higher than those in the normal control group and schizophrenia,and the difference was statistically significant(P<0.01).High-density lipoprotein in schizophrenia with the cerebral infarction group was significantly reduced,and the low-density lipoprotein was significantly increased in the schizophrenia with cerebral infarction group,the difference was statistically significant(P<0.05);2.The miR-33a level in the schizophrenia combined with cerebral infarction group was significantly higher than that of the schizophrenia group and the normal control group.The one-way analysis of variance showed statistical significance(P<0.01).The expression level of miR-494a increased in the schizophrenia complicated with cerebral infarction group,and single-factor analysis of variance was not statistically significant;3.ROC curve analysis of miR-33a:miR-33a was more valuable in the diagnosis of schizophrenia complicated with cerebral infarction.High,80.7%area under the curve,95%confidence interval(69.1%-92.4%),area under the miR-33 curve in schizophrenia group is 68.9%,95%confidence interval(53.7%-84.1%).Conclusion:The lipid metabolism of patients with schizophrenia complicated with cerebral infarction is significantly abnormal compared with normal people and patients with simple schizophrenia.The expression of miR-33a is significantly higher in patients with schizophrenia complicated with cerebral infarction,suggesting that miR-33a can be used as a risk indicator of early diagnosis and intervention of schizophrenia with cerebral infarction in patients with may be used as target genes for treatment.Objective To study the disease-gene relationship of obsessive-compulsive disorder and autism spectrum disorders,explore the genetic risk co-occurring genes of the two diseases,and further deepen the understanding of the biological mechanism of obsessive-compulsive disorderMethod.Obtain ASD and OCD disease-gene relationship data through large-scale literature search,and establish a database.First use Pathway Studio to analyze large-scale literature data to retrieve common genes related to two diseases Then ASD and OCD gene expression datasets were used to detect these disease-related genes in order to find possible new common genes,and then functional network analysis was carried out to explore the pathogenic mechanism of related genes based on biological channels and protein interactions.At the same time,in order to further verify the stability of the data,two batches of literature data updated in August 2017 and March 2019 were analyzed,and the data results were analyzed comprehensively.Results 1.Based on the database in 2017,there are 81 genes associated with obsessive-compulsive disorder and a total of 529 related genes associated with ASD,with 47 genes significantly overlapping in the two diseases.Based on the database updated in 2019,there are 86 genes associated with OCD and 624 genes associated with ASD,of which 43 genes overlap.2.Gene enrichment showed that among the common gene sets,there were 19 pathways/gene sets related to nervous system,5 genes related to brain function development,9 genes related to behavior and 13,genes related to neurotransmitters.In the database updated in 2019,the pathways of 43 genes were the same as those in 2017.The genes showed memory-related neural pathways in 2019,replacing the transsynaptic signaling neural pathways in 2017.3.Gene network analysis showed that there were both ASD and OCD disease processes in 25 gene regulatory networks based on the genome analysis in 2017.In the 2019 genome correlation analysis,23 common gene networks were found,further analysis of the shortest path to related genes showed that TSPO,CDh2,ADcy8,APOE,TORI A,OLig2,DISp1 and SETd1A had statistical significance.These genes were directly related to OCD and ASD,and there was a common biological pathway to regulate the neuropathological mechanism of ASD and OCD.Conclusion OCD and ASD have common genetic risk factors at the genetic level,which further confirms the biological basis of the common clinical pathological features of ASD and OCD.TSPO,APOE,CDH2,ADCY8,TOR1A,OLIG2,DISP1 and SETD1A may be the common risk genes of obsessive-compulsive disorder and autism.The study provides the common biological basis of obsessive-compulsive disorder and autism at the genetic level,and further deepens the understanding of the common biological mechanism of OCD-ASD,which provides a basis for further use of new potential risk genes for the study of ASD.Objective To explore the relationship between obsessive-compulsive disorder(OCD)and eating disorder(ED)at the genetic level,and to deepen the understanding of the common genetic basis of obsessive-compulsive disorder,and identify new potential risk genes.Methods First,search for related obsessive-compulsive disorder,eating disorder gene related data and gene expression data,and establish a database,and then use the expression data obtained from obsessive-compulsive disorder and eating disorder patients and healthy controls to identify potential new common risk genes for ED and OCD And biological pathways.Further conduct gene-disease-drug-relationship network analysis to study the potential pathogenic significance of new common genes to ED and OCD and the possible functional associations and pathological pathways of genes.Results 1.Gene expression was detected in 133 subjects(15 patients with ED,16 patients with obsessive-compulsive disorder and 102 normal controls).21 of the genes related to obsessive-compulsive disorder and ED overlap.Gene enrichment method showed that 7 pathways(13 overlapping genes)were related to behavior,5 pathways(14 overlapping genes)were related to nervous system,4 pathways(17 overlapping genes)were related to drug efficacy,3 pathways(5 overlapping genes)were related to neurotransmitters,2 pathways(8 overlapping genes)were related to brain functional development,and 1 pathway(9 overlapping genes)was related to cell proliferation.2.Gene expression analysis revealed that four new common important genes of obsessive-compulsive disorder and ED:OXTR,GAD2 and NPY,GRIL3;OXTR,GAD2 and NPY showed a strong functional connection with OCD through multiple genes and small molecular/drug pathways.GRIK3 also showed an association with ED by regulating ED-related diseases.Conclusion There is a significant association between OCD and ED at the genetic level,and they have common core symptoms and a common biological basis.OXTR,GAD2,NPY and GRIK3 are new potential common risk genes of OCD and ED,which provide a basis for the follow-up study of genetic correlation of OCD-ED.