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 Bone mineral density. The EFO term bone density 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:
U Styrkarsdottir, G Thorleifsson, P Sulem, DF Gudbjartsson, A Sigurdsson, A Jonasdottir, A Jonasdottir, A Oddsson, A Helgason, OT Magnusson, GB Walters, ML Frigge, HT Helgadottir, H Johannsdottir, K Bergsteinsdottir, MH Ogmundsdottir, JR Center, TV Nguyen, JA Eisman, C Christiansen, E Steingrimsson, JG Jonasson, L Tryggvadottir, GI Eyjolfsson, A Theodors, T Jonsson, T Ingvarsson, I Olafsson, T Rafnar, A Kong, G Sigurdsson, G Masson, U Thorsteinsdottir, K Stefansson
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
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
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
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
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
DEG methadone human cortical organoids cell line A_pvalue
Description:
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
DEG methadone human cortical organoids cell line A_qvalue
Description:
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
This gene set comprises 137 genes that were significantly expressed in the NA during the experiment. Background: The nuclear accumbens (NA) and amygdale (Amyg) of inbred alcohol-preferring mice were examined for differential gene expression and it findings suggest that changes in gene expression in the ACB of iP rats are associated with the reinforcing effects of ethanol (EtOH).
Striatum Gene Expression Correlates for HOTPLATE_MEANOF2 measured in BXD RI Females obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The HOTPLATE_MEANOF2 measures Thermal Nociception Hot Plate Avg of 2Trials under the domain Pain. 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
Hippocampus Gene Expression Correlates for COCA_BASE_DRUG measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The COCA_BASE_DRUG measures 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
Hippocampus Gene Expression Correlates for COCA_TIME_BASELINE measured in BXD RI Females obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The COCA_TIME_BASELINE measures Cocaine CPP - Proportion of time spent in conditioned side prior to conditioning 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
Total cellular RNA from Th0 and Th17 cells were subjected to microarray analysis. Fold induction was represented by the ratio of normalized gene expression in Th17 cells versus the expression in Th0 cells.
QTL for ethanol consumption on Chr2 at D2Mit14 (88.50 Mbp , Build 37)
Description:
ethanol consumption spans 63.50 - 113.50 Mbp (NCBI Build 37) on Chr2. 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 ethanol induced locomotor activity on Chr2 at D2Mit94 (94.37 Mbp , Build 37)
Description:
ethanol induced locomotor activity spans 69.37 - 119.37 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Hitzemann R, Cipp L, Demarest K, Mahjubi E, McCaughran J Jr
QTL for activity response to ethanol on Chr2 at NA (129.21 Mbp , Build 37)
Description:
activity response to ethanol spans 104.21 - 154.21 Mbp (NCBI Build 37) on Chr2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Chronic cocaine - Cocaine-paired (conditioned place preference) vs. Control (saline or cocaine-non-paired) DNA microarray All genes on microarray presented After the pre-conditioning phase where animals were allowed access to either compartment for 15 minutes for 4 consecutive days, the conditioning phase for the cocaine-paired groups and cocaine non-paired groups began, consisting of eight subsequent daily sessions. For both groups, cocaine (10 mg / kg) or saline injections were administered on alternate days. For the cocaine-paired groups, rats were immediately placed in one of the two compartments for 30 min with the door in place restricting a z transformation followed by z test and anova followed by Student-Newman-Keuls' post hoc test. Gene expression profile was assessed 24 h after the last conditioning session that corresponded to 48 h after last cocaine exposure, when drug has been eliminated from the body and transient transcriptional changes are likely to be minimal. Therefore, changes in gene expression at this time-point are likely to reflect longer lasting adaptations that may account for maintenance of cocaine-induced memories. The complete lists of normalized gene expression values for the hippocampus of saline-treated, cocaine non-paired and cocaine-paired groups are presented. Analyses revealed that 214 transcripts were differentially regulated in the hippocampus of cocaine-paired rats vs. non-paired and saline-treated controls. Cocaine-induced conditioned place preference caused significant increases in the expression of 151 genes and caused decreases in the expression of 63 genes. (NIF Table ID 130.1 [83])
Authors:
Krasnova IN, Li SM, Wood WH, McCoy MT, Prabhu VV, Becker KG, Katz JL, Cadet JL
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