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 Optic cup area. The EFO term optic cup area 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.
Authors:
H Springelkamp, A Mishra, PG Hysi, P Gharahkhani, R Höhn, CC Khor, JN Cooke Bailey, X Luo, WD Ramdas, E Vithana, V Koh, S Yazar, L Xu, H Forward, LS Kearns, N Amin, AI Iglesias, KS Sim, EM van Leeuwen, A Demirkan, S van der Lee, SC Loon, F Rivadeneira, A Nag, PG Sanfilippo, A Schillert, PT de Jong, BA Oostra, AG Uitterlinden, A Hofman, T Zhou, KP Burdon, TD Spector, KJ Lackner, SM Saw, JR Vingerling, YY Teo, LR Pasquale, RC Wolfs, HG Lemij, ES Tai, JB Jonas, CY Cheng, T Aung, NM Jansonius, CC Klaver, JE Craig, TL Young, JL Haines, S MacGregor, DA Mackey, N Pfeiffer, TY Wong, JL Wiggs, AW Hewitt, CM van Duijn, CJ Hammond
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
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
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
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_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.
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.
Whole Brain Gene Expression Correlates for ACTI15_SAL measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI15_SAL measures Distance traveled (cm) during the third five minute bin after saline under the domain Ethanol. 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
Cerebellum Gene Expression Correlates for AMCNT180 measured in BXD RI Females obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The AMCNT180 measures Morphine photocell counts minutes 165-180 under the domain Morphine. 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
Striatum Gene Expression Correlates for COCA_TEST_DRUG measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TEST_DRUG measures Cocaine CPP- Time (s) in drug-paired compartment a under the domain Cocaine. 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
Striatum Gene Expression Correlates for COCA_TEST_DRUG measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TEST_DRUG measures Cocaine CPP- Time (s) in drug-paired compartment a under the domain Cocaine. 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
Striatum Gene Expression Correlates for COCA_TIME_COND_CHG measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TIME_COND_CHG measures Cocaine CPP - difference in time spent relative to baseline drug exposure under the domain Cocaine. 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
Striatum Gene Expression Correlates for COCA_TIME_COND_CHG measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TIME_COND_CHG measures Cocaine CPP - difference in time spent relative to baseline drug exposure under the domain Cocaine. 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
Striatum Gene Expression Correlates for COCA_TIME_PCT_CHANGE measured in BXD RI Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The COCA_TIME_PCT_CHANGE measures Cocaine CPP - difference in percent test time spent relative to preconditioning under the domain Cocaine. 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
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