List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Intraocular pressure. The EFO term intraocular pressure measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.
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.
Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
Data from GEO GSE194368 and analyzed using GEO2R, only top gene shown. Authors identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators and downstream systems may represent viable therapeutic targets to treat the “stress side” of OUD.
Authors:
Stephanie A Carmack, Janaina C M Vendruscolo, M Adrienne McGinn, Jorge Miranda-Barrientos, Vez Repunte-Canonigo, Gabriel D Bosse, Daniele Mercatelli, Federico M Giorgi, Yu Fu, Anthony J Hinrich, Francine M Jodelka, Karen Ling, Robert O Messing, Randall T Peterson, Frank Rigo, Scott Edwards, Pietro P Sanna, Marisela Morales, Michelle L Hastings, George F Koob, Leandro F Vendruscolo
The dataset used in this study (Bulk RNA-Seq) was previously published and can be found at NCBI GEO (GSE182321), this analysis was conducted by GEO2R to compare control and OUD samples, only top differentially expressed genes are reported. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.
The dataset used in this study (Bulk RNA-Seq) was previously published and can be found at NCBI GEO (GSE182321), this analysis was conducted by GEO2R to compare control and OUD samples, only top differentially expressed genes are reported. To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, Ryan W Logan
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, Ryan W Logan
Transcriptional alterations in dorsolateral prefrontal cortex and nucleus accumbens implicate neuroinflammation and synaptic remodeling in opioid use disorder. Transcriptomic profile of 20 control subjects and 20 OUD subjects in brain region DLPFC and NAC. Analyzed using GEO2R (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174409) separately for each brain region, comparing OUD and control samples.
Authors:
Xiangning Xue, Wei Zong, Jill R Glausier, Sam-Moon Kim, Micah A Shelton, BaDoi N Phan, Chaitanya Srinivasan, Andreas R Pfenning, George C Tseng, David A Lewis, Marianne L Seney, 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 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.
Human induced pluripotent stem cell (iPSC) lines, A and B, derived from two healthy adult male individuals, were used to generate hCOs for RNA-sequencing. Methodone treatment began on Day 9 of organoid culture, the first day of the neural proliferation stage, and concluded at Day 60. Nuclease-free water was used as a vehicular control. Cortical organoids were collected 2 months (60 days) after initiating organoid culture. Each well of hCOs (15–20 organoids) was a separate biological replicate for a given treatment condition (i.e., treated or untreated). RNA was extracted from frozen organoid pellets using the Direct-Zol Miniprep Plus Kit (Zymo, Irvine, CA) according to the manufacturer’s instructions. Samples were multiplexed and sequenced on the Illumina NovaSeq 6000 S4 to produce approximately 100 million, 100 base pair, paired end reads per sample. 3 control and 3 methadone-treated samples were sequenced from cell line A, and 4 control and 4 treated samples from cell line B. Raw fastq file quality assessment and read alignment to the hg19 genome (GRCh37, RefSeq GCF_000001405.13) were performed. Significantly differentially expressed genes (DEGs) were selected based on the confident effect size of their log2(Fold Change) values at FDR<0.05. Genes presented are without cutoffs and were obtained using the GEO2R tool by GW curators (GEO accession: GSE210682).
Authors:
Ila Dwivedi, Andrew B Caldwell, Dan Zhou, Wei Wu, Shankar Subramaniam, Gabriel G Haddad
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