Dysregulation of NRSF/REST via EHMT1 is associated with psychiatric disorders and Kleefstra syndrome, Z scores
Description:
EHMT1 is an epigenetic repressor that is causal for Kleefstra Syndrome (KS), a neurodevelopmental disorder (NDD) leading to intelectual disability, and is associated with schizophrenia. Here, the researchers aim to show we show that reduced EHMT1 activity decreases NRSF/REST protein leading to abnormal neuronal gene expression and progression of neurodevelopment in human iPSC. Five induced pluripotent stem cell samples (from fibroblasts of adult, male, skin) were used. The stem cells were gifted from: Lieber Institute for Brain Development, Johns Hopkins Medical Campus. Total RNA extracted from a control hiPSC line and control cells treated for 72h with various concentrations of UNC0638 i.e 50, 100, 200 or 250nM as a model for Kleefstra syndrome. Polyadenylated adaptors were ligated to the 3′-end, 5′-adaptors were then ligated, and the resulting RNAs were reverse transcribed to generate cDNA that can be amplified by PCR. The amplified product was run on low range ultra agarose in TBE buffer and a size-selection was performed to ensure that the cDNA used for sequencing primarily contains miRNAs rather than other RNA contaminants. Expression values were calculated by the method detailed in 'HBA-DEALS: accurate and simultaneous identification of differential expression and splicing using hierarchical Bayesian analysis' (Genome Biol. 2020, PMID: 32660516), and Z scores calculated. Genes were annotated as Ensembl gene ids. SRA Study id ERP130338.
Postmortem tissue samples of the dorsolateral prefrontal cortex (DLPFC) from 153 deceased individuals (Mage = 35.4; 62% male; 77% European ancestry). Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 psychiatric controls, and 28 normal controls. Whole transcriptome RNA-sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses were adjusted for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness using quality surrogate variables. Weighted correlation network analysis and gene set enrichment analyses also were conducted.
Authors:
David W Sosnowski, Andrew E Jaffe, Ran Tao, Amy Deep-Soboslay, Chang Shu, Sarven Sabunciyan, Joel E Kleinman, Thomas M Hyde, Brion S Maher
Opioid controls_human_ dorsolateral prefrontal cortex and nucleus accumbens_coefficient
Description:
RNA sequencing on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc) from unaffected comparison subjects (n = 20) and subjects diagnosed with opioid use disorder OUD (n = 20). Transcriptomic analyses identified differentially expressed transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric orderlap.transcriptional differences by brain region in unaffected comparison subjects, finding unique transcriptional profiles in the DLPFC and NAc
Authors:
Marianne L Seney, Sam-Moon Kim, Jill R Glausier, Mariah A Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Zachary Freyberg, Ryan W Logan
Opioid controls_human_ dorsolateral prefrontal cortex and nucleus accumbens_qvalue
Description:
RNA sequencing on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc) from unaffected comparison subjects (n = 20) and subjects diagnosed with opioid use disorder OUD (n = 20). Transcriptomic analyses identified differentially expressed transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric orderlap.transcriptional differences by brain region in unaffected comparison subjects, finding unique transcriptional profiles in the DLPFC and NAc
Authors:
Marianne L Seney, Sam-Moon Kim, Jill R Glausier, Mariah A Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Zachary Freyberg, Ryan W Logan
Opioid use disorder_human_dorsolateral prefrontal cortex_coefficient
Description:
RNA sequencing on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc) from unaffected comparison subjects (n = 20) and subjects diagnosed with opioid use disorder OUD (n = 20). Transcriptomic analyses identified differentially expressed transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric orderlap.transcriptional differences by brain region in unaffected comparison subjects, finding unique transcriptional profiles in the DLPFC and NAc
Authors:
Marianne L Seney, Sam-Moon Kim, Jill R Glausier, Mariah A Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Zachary Freyberg, Ryan W Logan
Opioid use disorder_human_nucleus accumbens_coefficient
Description:
RNA sequencing on the dorsolateral prefrontal cortex (DLPFC) and nucleus accumbens (NAc) from unaffected comparison subjects (n = 20) and subjects diagnosed with opioid use disorder OUD (n = 20). Transcriptomic analyses identified differentially expressed transcripts and investigated the transcriptional coherence between brain regions using rank-rank hypergeometric orderlap.transcriptional differences by brain region in unaffected comparison subjects, finding unique transcriptional profiles in the DLPFC and NAc
Authors:
Marianne L Seney, Sam-Moon Kim, Jill R Glausier, Mariah A Hildebrand, Xiangning Xue, Wei Zong, Jiebiao Wang, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Zachary Freyberg, Ryan W Logan
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Corradin et al. 2022_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Corradin et al. 2022_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Mendez et al 2021_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Seney et al 2021_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Seney et al 2021_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Sosnowski et al 2022_log2FC
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
Opioid_human_dorsolateral prefrontal cortex_reanalysis of Sosnowski et al 2022_qvalue
Description:
doi: https://doi.org/10.1101/2024.01.12.24301153. This study is a re-analysis of publicly available data and a meta-analysis investigating differential gene expression associated with opioid use disorder from Corradin et al. 2022 (PMID: 35301427); Mendez et al. 2021 (PMID: 34385598); Seney et al. 2021 (PMID: 34380600); and Sosnowski et al. 2022 (PMID:36845993 ). All four of these studies used human postmortem dorsolateral prefrontal cortex (DLPFC) brain tissue from donors identified as dying from OOD through toxicology assays administered by forensic scientists and phenotypic evidence of opioid addiction. Each of these independent studies had modest sample sizes (N = 40-153) and compared bulk RNA-seq data from individuals who died from OOD to individuals who died from non–drug use causes.
This gene sets comprises 30 genes that showed decreased expression in the adult rats exposed to prenatal ethanol. Background: By comparing gene expression during gestational ethanol exposure to gene expression of neurotransmission genes in the olfactory bulb of adolescent rats, study suggests that ethanol exposure via maternal diet predicted the propensity to ingest ethanol during adolescence.
Neocortex Gene Expression Correlates for LD_DARK_TIME measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LD_DARK_TIME measures Light-Dark Box Total seconds spent in dark compartment under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
Neocortex Gene Expression Correlates for LD_LIGHT_TIME measured in BXD RI Females obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The LD_LIGHT_TIME measures Light- Dark Box Total seconds spent in light compartment under the domain Basal Behavior. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
cocaine related behavior 10 (Cocrb10) spans 93.149752 - 143.149752 Mbp (NCBI Build 37) on Chr 9. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for METH responses for home cage activity on Chr9 at Gst2-3 (90.12 Mbp , Build 37)
Description:
METH responses for home cage activity spans 65.12 - 115.12 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for differences in cocaine responsiveness on Chr9 at D9M!t12 (94.40 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 69.40 - 119.40 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for body temperature on Chr9 at D9Mit12 (103.09 Mbp , Build 37)
Description:
METH responses for body temperature spans 78.09 - 128.09 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
alcohol response 4 (a.k.a. high-dose ethanol actions) is associated with neurotensin immunoreactivity and sleep time after alcohol administration mapped to 55 cM on mouse Chromosome 9 near D9Mit12 (P=0.0006). This locus is named Alcrsp4 (alcohol response 4). Potential candidate genes found in this region are Chrna3 and Gnai2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
GeneWeaver