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 Crohn's disease. The EFO term Crohn's disease 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:
A Julià, E Domènech, E Ricart, R Tortosa, V García-Sánchez, JP Gisbert, P Nos Mateu, A Gutiérrez, F Gomollón, JL Mendoza, E Garcia-Planella, M Barreiro-de Acosta, F Muñoz, M Vera, C Saro, M Esteve, M Andreu, A Alonso, M López-Lasanta, L Codó, JL Gelpí, AC García-Montero, J Bertranpetit, D Absher, J Panés, S Marsal
Genes associated with Homo sapiens that interact with the MeSH term 'Valproic Acid' (D014635). Incorporates data from 1238 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
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 Schizophrenia. The EFO term schizophrenia 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.
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.
H-MAGMA genes in iPSC neurons from EXT GWAS_pvalue
Description:
"We amassed a set of phenotype-specific GWAS summary statistics for different externalizing phenotypes, either by collecting existing results or by performing GWAS in UK Biobank (UKB) (Supplementary Information section 2). The multivariate method “genomic structural equation modelling” (Genomic SEM) was applied on a subset of the summary statistics (N = 53,293–1,251,809) deemed adequately heritable and statistically powered, in order to estimate a series of model specifications representing
different genetic factor structures (Supplementary Information section 3). The best-fitting and most parsimonious solution (“the preferred model specification”) specified a
single common genetic factor with seven indicator phenotypes (which we hereafter refer to as “the latent genetic externalizing factor”, or simply, “the externalizing factor”). The 7 phenotypes eventually used to estimate the latent genetic externalizing factor were (1) ADHD, (2) age at first sexual intercourse (FSEX), (3) problematic alcohol use (ALCP), (4) lifetime cannabis use (CANN), (5) lifetime smoking initiation (SMOK), (6) general risk tolerance (RISK), and (7) number of sexual partners (NSEX). We used an extension of MAGMA v1.08, “Hi-C coupled MAGMA” or “H-MAGMA” (version June 14, 2019), to assign non-coding (intergenic and intronic) SNPs to cognate genes based on their chromatin interactions. Exonic and promoter SNPs were assigned to genes based on physical position. We used four Hi-C datasets derived from adult brain, fetal brain, and iPSC derived neurons and astrocytes. We evaluated Bonferroni corrected P-value thresholds, adjusted for multiple testing within each analysis (one-sided P < 9.84×10–7). Displaying genes with P value less than 1E–5. From supplementary table 19."
Authors:
Richard Karlsson Linnér, Travis T Mallard, Peter B Barr, Sandra Sanchez-Roige, James W Madole, Morgan N Driver, Holly E Poore, Ronald de Vlaming, Andrew D Grotzinger, Jorim J Tielbeek, Emma C Johnson, Mengzhen Liu, Sara Brin Rosenthal, Trey Ideker, Hang Zhou, Rachel L Kember, Joëlle A Pasman, Karin J H Verweij, Dajiang J Liu, Scott Vrieze, , Henry R Kranzler, Joel Gelernter, Kathleen Mullan Harris, Elliot M Tucker-Drob, Irwin D Waldman, Abraham A Palmer, K Paige Harden, Philipp D Koellinger, Danielle M Dick
Sig. H-MAGMA genes in iPSC neurons from EXT GWAS_pvalue
Description:
"We amassed a set of phenotype-specific GWAS summary statistics for different externalizing phenotypes, either by collecting existing results or by performing GWAS in UK Biobank (UKB) (Supplementary Information section 2). The multivariate method “genomic structural equation modelling” (Genomic SEM) was applied on a subset of the summary statistics (N = 53,293–1,251,809) deemed adequately heritable and statistically powered, in order to estimate a series of model specifications representing different genetic factor structures (Supplementary Information section 3). The best-fitting and most parsimonious solution (“the preferred model specification”) specified a single common genetic factor with seven indicator phenotypes (which we hereafter refer to as “the latent genetic externalizing factor”, or simply, “the externalizing factor”). The 7 phenotypes eventually used to estimate the latent genetic externalizing factor were (1) ADHD, (2) age at first sexual intercourse (FSEX), (3) problematic alcohol use (ALCP), (4) lifetime cannabis use (CANN), (5) lifetime smoking initiation (SMOK), (6) general risk tolerance (RISK), and (7) number of sexual partners (NSEX). We used an extension of MAGMA v1.08, “Hi-C coupled MAGMA” or “H-MAGMA” (version June 14, 2019), to assign non-coding (intergenic and intronic) SNPs to cognate genes based on their chromatin interactions. Exonic and promoter SNPs were assigned to genes based on physical position. We used four Hi-C datasets derived from adult brain, fetal brain, and iPSC derived neurons and astrocytes. We evaluated Bonferroni corrected P-value thresholds, adjusted for multiple testing within each analysis. Genes with significant corrected p-values shown here (one-sided P < 9.84×10–7). From supplementary table 19."
Authors:
Richard Karlsson Linnér, Travis T Mallard, Peter B Barr, Sandra Sanchez-Roige, James W Madole, Morgan N Driver, Holly E Poore, Ronald de Vlaming, Andrew D Grotzinger, Jorim J Tielbeek, Emma C Johnson, Mengzhen Liu, Sara Brin Rosenthal, Trey Ideker, Hang Zhou, Rachel L Kember, Joëlle A Pasman, Karin J H Verweij, Dajiang J Liu, Scott Vrieze, , Henry R Kranzler, Joel Gelernter, Kathleen Mullan Harris, Elliot M Tucker-Drob, Irwin D Waldman, Abraham A Palmer, K Paige Harden, Philipp D Koellinger, Danielle M Dick
Cerebellum Gene Expression Correlates for TAILCLIP_LAT_SEC measured in BXD RI Females & Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The TAILCLIP_LAT_SEC measures Mechanical Nociception - Tail Clip Test 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
Neocortex Gene Expression Correlates for SVCOUNT15 measured in BXD RI Females & Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The SVCOUNT15 measures Open Field rears 0-15 min post saline 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
Cerebellum Gene Expression Correlates for TAILCLIP_LAT_SEC measured in BXD RI Males obtained using SJUT Cerebellum mRNA M430 (Mar05) RMA. The TAILCLIP_LAT_SEC measures Mechanical Nociception - Tail Clip Test 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 ZM_ACTIVITY measured in BXD RI Females & Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The ZM_ACTIVITY measures Zero Maze - Total Activity count; number of beam breaks under the domain Basal Behavior. 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
Neocortex Gene Expression Correlates for COCA_TEST_VEHICLE measured in BXD RI Males obtained using GeneNetwork Neocortex ILM6v1.1 (Feb08) RankInv. The COCA_TEST_VEHICLE measures Cocaine CPP - Time (s) in saline 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 LM_PAIR1 measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_PAIR1 measures Activity during 1st tone shock pairing under the domain Basal Behavior. 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
Whole Brain Gene Expression Correlates for URINE measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The URINE measures Novel Open Field Number of urinations 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
Differentially expressed in the Nucleus accumbens following 24 hr continuous 9.5g/kg/day alcohol drinking vs. water drinking in alcohol preferring rats. Estimated BAC in the alcohol exposed group was > 85mg%. The 406 significanlty different probe sets represent 374 uniquely named genes, with most gene expression differences in the range of 1.1-1.3 fold.
cocaine related behavior 14 (Cocrb14) spans 43.765096 - 93.765096 Mbp (NCBI Build 37) on Chr 15. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
cocaine related behavior 15 (Cocrb15) spans 70.807693 - 120.807693 Mbp (NCBI Build 37) on Chr 15. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for alcohol acceptance on Chr15 at D15Mit60 (57.48 Mbp , Build 37)
Description:
alcohol acceptance spans 32.48 - 82.48 Mbp (NCBI Build 37) on Chr15. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
McClearn GE, Tarantino LM, Rodriguez LA, Jones BC, Blizard DA, Plomin R
QTL for cocaine related behavior on Chr15 at D15Mit3 (83.88 Mbp , Build 37)
Description:
cocaine related behavior spans 58.88 - 108.88 Mbp (NCBI Build 37) on Chr15. 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 alcohol consumption on Chr15 at D15Mit105 (87.33 Mbp , Build 37)
Description:
alcohol consumption spans 62.33 - 112.33 Mbp (NCBI Build 37) on Chr15. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Vadasz C, Saito M, Gyetvai B, Mikics E, Vadasz C 2nd
QTL for cocaine induced activation on Chr15 at NA (92.79 Mbp , Build 37)
Description:
cocaine induced activation spans 67.79 - 117.79 Mbp (NCBI Build 37) on Chr15. 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 METH responses for home cage activity on Chr15 at D15Mit1 (93.20 Mbp , Build 37)
Description:
METH responses for home cage activity spans 68.20 - 118.20 Mbp (NCBI Build 37) on Chr15. 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 cocaine related behavior on Chr15 at D15Ncvs29 (95.81 Mbp , Build 37)
Description:
cocaine related behavior spans 70.81 - 120.81 Mbp (NCBI Build 37) on Chr15. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
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