Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder

Morimoto, Yoshiro; Shimada-Sugimoto, Mihoko; Otowa, Takeshi; Yoshida, Shintaro; Kinoshita, Akira; Mishima, Hiroyuki; Yamaguchi, Naohiro; Mori, T.; Imamura, Akira; Ozawa, Hiroki; Kurotaki, Naohiro; Ziegler, Christiane; Domschke, Katharina; Deckert, Jürgen; Umekage, Tadashi; Tochigi, Mamoru; Kaiya, Hisanobu; Okazaki, Yuji; Tokunaga, Katsushi; Sasaki, Tsukasa; Yoshiura, Koh-ichiro; Ono, Shinji

doi:10.1038/s41398-017-0088-0

Cited by 16 publications

(9 citation statements)

References 38 publications

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“…It was known to regulate synapse formation, synapse elimination (Ou et al, 2010;Park et al, 2011), hippocampal neurons related pathways, and hippocampal long-term potentiation (Cho et al, 2015;Joe et al, 2017). PLA2G4E was reported to be strongly expressed in the brain, especially in neurons (Ogura et al, 2016), and was associated with neurobehavioral disorders (Everson et al, 2019;Morimoto et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

et al. 2020

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Background: Recent studies have identified several molecular subgroups of medulloblastoma associated with distinct clinical outcomes; however, no robust gene signature has been established for prognosis prediction. Our objective was to construct a robust gene signature-based model to predict the prognosis of patients with medulloblastoma. Methods: Expression data of medulloblastomas were acquired from the Gene Expression Omnibus (GSE85217, n = 763; GSE37418, n = 76). To identify genes associated with overall survival (OS), we performed univariate survival analysis and least absolute shrinkage and selection operator (LASSO) Cox regression. A risk score model was constructed based on selected genes and was validated using multiple datasets. Differentially expressed genes (DEGs) between the risk groups were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) analyses were performed. Network modules and hub genes were identified using Cytoscape. Furthermore, tumor microenvironment (TME) was evaluated using ESTIMATE algorithm. Tumor-infiltrating immune cells (TIICs) were inferred using CIBERSORTx. Results: A 13-gene model was constructed and validated. Patients classified as high-risk group had significantly worse OS than those as low-risk group (Training set: p < 0.0001; Validation set 1: p < 0.0001; Validation set 2: p = 0.00052). The area under the curve (AUC) of the receiver operating characteristic (ROC) analysis indicated a good performance in predicting 1-, 3-, and 5-year OS in all datasets. Multivariate analysis integrating clinical factors demonstrated that the risk score was an independent predictor for the OS (validation set 1: p = 0.001, validation set 2: p = 0.004). We then identified 265 DEGs between risk groups and PPI analysis predicted modules that were highly related to central nervous system and embryonic development. The risk score was significantly correlated with programmed deathligand 1 (PD-L1) expression (p < 0.001), as well as immune score (p = 0.035), stromal score (p = 0.010), and tumor purity (p = 0.010) in Group 4 medulloblastomas. Correlations between the 13-gene signature and the TIICs in Sonic hedgehog and Group 4 medulloblastomas were revealed.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

et al. 2020

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“…It is considered to be related to neural structure and function, a neurobehavioral disorder in research [60]. Some literature suggests that this gene may be a risk gene for panic disorder [61], there is also some literature indicating that there is a certain relationship between the occurrence of depression [62]. Cytosolic phospholipase A2 is closely related to axonal proliferation and excitotoxic damage under pathological conditions [63].…”

Section: Discussionmentioning

confidence: 99%

mRNA and microRNA profiles in the amygdala are relevant to Susceptible and Resilient mice induced by psychological stress

Sun¹,

Lu²,

Yang³

et al. 2020

Preprint

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Background Severe or prolonged stress increases the risk to develop psychopathologies. An individual's perception of stress exposure varies greatly, as do its consequences. Numerous individuals demonstrate resilience to psychological stress. The mRNA and microRNA profiles of stress susceptibility and resilience induced by psychological stress in the amygdala remain to be elucidated. Methods Psychological stress to an observer was given by witnessing the attacks of the aggressor on the similar. After five days of psychological stress, the degree of fear memory and anxiety of mice were measured by social interaction test and elevated plus-maze (EPM). mRNA and microRNA profiles were quantified by high-throughput sequencing in amygdala tissues harvested from Control, Susceptible and Resilient mice. Results In the amygdala from Susceptible mice versus Resilient mice, the upregulation of Peptide, Thyrotropin-releasing hormone, and ECM receptor, Glutamatergic synapse, Cytokine-cytokine receptor interaction, Long-term depression, PI3K-Akt, Oxytocin, GnRH, HIF-1, Estrogen, Calcium signaling pathways may be related to psychological stress-induced susceptibility, and the downregulation may be related to resilience. The downregulation of Adrenergic synapse, Adherens junction, Wnt, Sphingolipid, B cell receptor, cAMP, Rap1, Toll-like receptor signaling pathways may be related to psychological stress-induced susceptibility, and the upregulation may be related to resilience. Results by sequencing mRNA and microRNA profiles are consistent, in which some of them are validated by qRT-PCR and dual-luciferase reporter assay. Conclusion Susceptible and Resilient induced by psychological stresses are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.

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“…This gene encodes for a calcium-dependent N-acyltransferase; experimental mouse models have implicated that it likely plays a critical role in endocannabinoid signaling in the nervous system 58 and thus differential regulation of this gene has implications for neurodevelopment and neurodegenerative disorders 59 . In human observational studies, placental CpGs within PLA2G4E have been observed to be differentially methylated in association with extremely preterm births 60 and genetic variants within the PLA2G4E gene have been implicated as a potential risk factor for neurodevelopmental problems such as panic disorder 61 . The protein encoded by GRIK3 is involved in presynaptic neurotransmission, and has been associated with developmental delay 62 , schizophrenia 63 , obsessive-compulsive disorder 64 , and depression 65 .…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

Everson

Marsit

O’Shea

et al. 2019

Sci Rep

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Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β 1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Some of the genes annotated to these CpGs included PLA2G4E , TRIM9 , GRIK3 , and MACROD2 , which have previously been associated with neurological structure and function, or with neurobehavioral disorders. These findings contribute to the existing evidence that neonatal epigenetic variations may be informative for infant neurobehavior.

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Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder

Cited by 16 publications

References 38 publications

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

Construction and Validation of a 13-Gene Signature for Prognosis Prediction in Medulloblastoma

mRNA and microRNA profiles in the amygdala are relevant to Susceptible and Resilient mice induced by psychological stress

Epigenome-wide Analysis Identifies Genes and Pathways Linked to Neurobehavioral Variation in Preterm Infants

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