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 Obesity-related traits. The EFO term body height 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:
AG Comuzzie, SA Cole, SL Laston, VS Voruganti, K Haack, RA Gibbs, NF Butte
This set describes genes whose transcription is upregulated in the whole blood of severe COVID-19 patients versus healthy donors. Genes listed in table S2 were entered using ENSEMBL Gene identifiers. Values are the reported log2 fold-change.
Authors:
Anna C Aschenbrenner, Maria Mouktaroudi, Benjamin Krämer, Marie Oestreich, Nikolaos Antonakos, Melanie Nuesch-Germano, Konstantina Gkizeli, Lorenzo Bonaguro, Nico Reusch, Kevin Baßler, Maria Saridaki, Rainer Knoll, Tal Pecht, Theodore S Kapellos, Sarandia Doulou, Charlotte Kröger, Miriam Herbert, Lisa Holsten, Arik Horne, Ioanna D Gemünd, Nikoletta Rovina, Shobhit Agrawal, Kilian Dahm, Martina van Uelft, Anna Drews, Lena Lenkeit, Niklas Bruse, Jelle Gerretsen, Jannik Gierlich, Matthias Becker, Kristian Händler, Michael Kraut, Heidi Theis, Simachew Mengiste, Elena De Domenico, Jonas Schulte-Schrepping, Lea Seep, Jan Raabe, Christoph Hoffmeister, Michael ToVinh, Verena Keitel, Gereon Rieke, Valentina Talevi, Dirk Skowasch, N Ahmad Aziz, Peter Pickkers, Frank L van de Veerdonk, Mihai G Netea, Joachim L Schultze, Matthijs Kox, Monique M B Breteler, Jacob Nattermann, Antonia Koutsoukou, Evangelos J Giamarellos-Bourboulis, Thomas Ulas,
This set describes genes whose transcription is upregulated in the whole blood of COVID-19 patients versus healthy donors. Genes listed in table S2 were entered using the core ENSEMBL Gene identifiers. Values are the reported log2 fold-change.
Authors:
Anna C Aschenbrenner, Maria Mouktaroudi, Benjamin Krämer, Marie Oestreich, Nikolaos Antonakos, Melanie Nuesch-Germano, Konstantina Gkizeli, Lorenzo Bonaguro, Nico Reusch, Kevin Baßler, Maria Saridaki, Rainer Knoll, Tal Pecht, Theodore S Kapellos, Sarandia Doulou, Charlotte Kröger, Miriam Herbert, Lisa Holsten, Arik Horne, Ioanna D Gemünd, Nikoletta Rovina, Shobhit Agrawal, Kilian Dahm, Martina van Uelft, Anna Drews, Lena Lenkeit, Niklas Bruse, Jelle Gerretsen, Jannik Gierlich, Matthias Becker, Kristian Händler, Michael Kraut, Heidi Theis, Simachew Mengiste, Elena De Domenico, Jonas Schulte-Schrepping, Lea Seep, Jan Raabe, Christoph Hoffmeister, Michael ToVinh, Verena Keitel, Gereon Rieke, Valentina Talevi, Dirk Skowasch, N Ahmad Aziz, Peter Pickkers, Frank L van de Veerdonk, Mihai G Netea, Joachim L Schultze, Matthijs Kox, Monique M B Breteler, Jacob Nattermann, Antonia Koutsoukou, Evangelos J Giamarellos-Bourboulis, Thomas Ulas,
GWAS: superior frontal gyrus grey matter volume measurement
Description:
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 Superior frontal gyrus grey matter volume. The EFO term superior frontal gyrus grey matter volume 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:
R Hashimoto, M Ikeda, F Yamashita, K Ohi, H Yamamori, Y Yasuda, M Fujimoto, M Fukunaga, K Nemoto, T Takahashi, M Tochigi, T Onitsuka, H Yamasue, K Matsuo, T Iidaka, N Iwata, M Suzuki, M Takeda, K Kasai, N Ozaki
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
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
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.
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.
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
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
We performed single-nuclei multiome profiling on postmortem caudate nucleus (CN) tissue from six individuals with cocaine use disorder (CocUD) and eight controls, all of African American ancestry. CocUD cases and controls were balanced according to age and sex. We performed single-nuclei ATAC-seq and RNA-seq using the 10x Genomics Multiome platform. Weighted nearest neighbor analysis resulted in an integrated UMAP depicting 13 clearly delineated cell types, including astrocytes, microglia, oligodendrocytes, oligodendrocyte precursor cells (OPC), endothelial cells and lymphocytes, as well as different GABAergic neurons, such as D1 and D2 medium spiny neurons (MSNs) and a small population of cholinergic neurons.
Authors:
Lea Zillich, Annasara Artioli, Veronika Pohořalá, Eric Zillich, Laura Stertz, Hanna Belschner, Ammar Jabali, Josef Frank, Fabian Streit, Diana Avetyan, Maja Völker, Svenja Müller, Anita Hansson, Thomas Meyer, Marcella Rietschel, Rainer Spanagel, Ana Oliveira, Consuelo Walss-Bass, Rick Bernardi, Philipp Koch, Stephanie Witt
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