To identify genetic differences in the EWcp of inbred mouse strains that differ in behaviors relevant to EWcp function, we used publicly available tools from the Allen Brain Atlas to identify 68 tran- scripts that were selectively expressed in the EWcp, and examined their expression within tissue punch microdissection samples containing the EWcp of adult male C57BL/6J (B6) and DBA/2J (D2) mice. Using 96-well quantitative real-time PCR (qPCR) arrays that included the EWcp-specific genes, several other genes of interest, and five housekeeping genes, we identified strain differences in expression of 11 EWcp-specific genes (BC023892, Btg3, Bves, Cart, Cck, Ghsr, Neto1, Postn, Ptprn, Rcn1, and Ucn), two immediate early genes (Egr1 and Fos), and one dopamine-related gene (Drd5). Statistics reported as p-value.
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 Thyroid hormone levels. The EFO term thyroxine 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:
E Porcu, M Medici, G Pistis, CB Volpato, SG Wilson, AR Cappola, SD Bos, J Deelen, M den Heijer, RM Freathy, J Lahti, C Liu, LM Lopez, IM Nolte, JR O'Connell, T Tanaka, S Trompet, A Arnold, S Bandinelli, M Beekman, S Böhringer, SJ Brown, BM Buckley, C Camaschella, AJ de Craen, G Davies, MC de Visser, I Ford, T Forsen, TM Frayling, L Fugazzola, M Gögele, AT Hattersley, AR Hermus, A Hofman, JJ Houwing-Duistermaat, RA Jensen, E Kajantie, M Kloppenburg, EM Lim, C Masciullo, S Mariotti, C Minelli, BD Mitchell, R Nagaraja, RT Netea-Maier, A Palotie, L Persani, MG Piras, BM Psaty, K Räikkönen, JB Richards, F Rivadeneira, C Sala, MM Sabra, N Sattar, BM Shields, N Soranzo, JM Starr, DJ Stott, FC Sweep, G Usala, MM van der Klauw, D van Heemst, A van Mullem, SH Vermeulen, WE Visser, JP Walsh, RG Westendorp, E Widen, G Zhai, F Cucca, IJ Deary, JG Eriksson, L Ferrucci, CS Fox, JW Jukema, LA Kiemeney, PP Pramstaller, D Schlessinger, AR Shuldiner, EP Slagboom, AG Uitterlinden, B Vaidya, TJ Visser, BH Wolffenbuttel, I Meulenbelt, JI Rotter, TD Spector, AA Hicks, D Toniolo, S Sanna, RP Peeters, S Naitza
We used publicly available tools from the Allen Brain Atlas to identify 68 tran- scripts that were selectively expressed in the EWcp, and examined their expression within tissue punch microdissection samples containing the EWcp of adult male C57BL/6J (B6) and DBA/2J (D2) mice. Using 96-well quantitative real-time PCR (qPCR) arrays that included the EWcp-specific genes, several other genes of interest, and five housekeeping genes, we identified strain differences in expression of 11 EWcp-specific genes (BC023892, Btg3, Bves, Cart, Cck, Ghsr, Neto1, Postn, Ptprn, Rcn1, and Ucn), two immediate early genes (Egr1 and Fos), and one dopamine-related gene (Drd5). All significant expression differ- ences were greater in B6 vs. D2 mice, and several of these were verified either at the protein level using immunohistochemistry (IHC) or in silico using microarray data sets from whole brain and other brain areas. Statistics reported in P-value.
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 Thyroid hormone levels. The EFO term thyroid stimulating hormone 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:
E Porcu, M Medici, G Pistis, CB Volpato, SG Wilson, AR Cappola, SD Bos, J Deelen, M den Heijer, RM Freathy, J Lahti, C Liu, LM Lopez, IM Nolte, JR O'Connell, T Tanaka, S Trompet, A Arnold, S Bandinelli, M Beekman, S Böhringer, SJ Brown, BM Buckley, C Camaschella, AJ de Craen, G Davies, MC de Visser, I Ford, T Forsen, TM Frayling, L Fugazzola, M Gögele, AT Hattersley, AR Hermus, A Hofman, JJ Houwing-Duistermaat, RA Jensen, E Kajantie, M Kloppenburg, EM Lim, C Masciullo, S Mariotti, C Minelli, BD Mitchell, R Nagaraja, RT Netea-Maier, A Palotie, L Persani, MG Piras, BM Psaty, K Räikkönen, JB Richards, F Rivadeneira, C Sala, MM Sabra, N Sattar, BM Shields, N Soranzo, JM Starr, DJ Stott, FC Sweep, G Usala, MM van der Klauw, D van Heemst, A van Mullem, SH Vermeulen, WE Visser, JP Walsh, RG Westendorp, E Widen, G Zhai, F Cucca, IJ Deary, JG Eriksson, L Ferrucci, CS Fox, JW Jukema, LA Kiemeney, PP Pramstaller, D Schlessinger, AR Shuldiner, EP Slagboom, AG Uitterlinden, B Vaidya, TJ Visser, BH Wolffenbuttel, I Meulenbelt, JI Rotter, TD Spector, AA Hicks, D Toniolo, S Sanna, RP Peeters, S Naitza
Postmortem human brain tissue from the caudate nucleus region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Postmortem human brain tissue from the putamen region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Postmortem human brain tissue from the ventral striatum from postmortem human brain tissue with Alcohol Use Disorder (AUD) region of a total of 48 individuals with Alcohol Use Disorder (AUD) and 51 control individuals were taken and RNA extracted from frozen tissue. Sequencing was carried out using the NovaSeq 6000 (Illumina) platform, and gene expression analysis was carried out with respect to AUD and control samples. Gene symbols from Entrez ids are used and Logbase2 FC as provided by the authors are annotated.
Authors:
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Differentially expressed genes from RPE compared to Normal Retina
Description:
Transcriptome profiling from macular retina and RPE/choroid samples from 27 unrelated eye tissue donors, was performed using RNA-sequencing. Human donor eye collection were obtained from Utah Lions Eye Bank within a 6-hour post-mortem interval and donors aged 60-90 years. Sample types were Normal Retina, Intermediate AMD Retina, Neovascular AMD Retina, Normal macular retina pigment epithelium (RPE), Intermediate AMD RPE, and Neovascular AMD RPE. Age Related Macular Degeneration (AMD) phenotyping was determined using the Age-Related Eye Disease Study (AREDS) severity grading scale, where AREDS category 0/1 was considered normal, AREDS category 3 intermediate AMD, and AREDS category 4b neovascular AMD. Samples from Normal RPE were compared to Normal Retina, and are presented with fold change > 1.5 and and P < 0.05. This gene set was annotated from the Supplementry Table of BioRxiv pre-print paper ‘Patterns of gene expression and allele-specific expression vary among macular tissues and clinical stages of Age-related Macular Degeneration’ by Zhang et.al (2022) doi: https://doi.org/10.1101/2022.12.19.521092
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
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 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.
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