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 Thoracic aortic aneurysms and dissections. The EFO term thoracic aortic aneurysm 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:
SA LeMaire, ML McDonald, DC Guo, L Russell, CC Miller, RJ Johnson, MR Bekheirnia, LM Franco, M Nguyen, RE Pyeritz, JE Bavaria, R Devereux, C Maslen, KW Holmes, K Eagle, SC Body, C Seidman, JG Seidman, EM Isselbacher, M Bray, JS Coselli, AL Estrera, HJ Safi, JW Belmont, SM Leal, DM Milewicz
Downregulated genes from TAA tissues of Fbn1(mgR/mgR) MFS male mice compared to WT at P16
Description:
Throracic Aortic Aneurysms (TAAs) are a major clinical feature of Marfan syndrome (MFS). It is associated with mutations in the MFN1 gene encoding the multifunctional extracellular matrix glycoprotein Fibrillin-1. TAAs are life-threatening pathologies characterized by progressive vessel dilations associated with smooth muscle (SMC) dysfunction, occasional localiized inflammatory infiltrates, and severe maladaptive extracellular matrix (ECM) remodelling that, together, predispose the arterial wall to dissection and rupture leading to premature death. For this geneset expression values were obtained from the GEO accession GSE128101, and the corresponding SRA study accession SRP188087. The control GEO sample accessions were GSM3673486, GSM3673487 and GSM3673488 (corresponding in the SRA to SRX5527666, SRX5527667 & SRX5527668) compared to the case GEO sample accessions GSM3673483, GSM3673484 and GSM3673485 (corresponding to SRA accessions SRX5527663, SRX552764 & SRX552765). 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 log base 2 of the fold change are presented with a FDR of <0.05. All ensembl gene ids were checked in MGI for duplicates. The strain background was C57BL/6J, and all mice were male and sacrificed at P16.
Authors:
Jens Hansen, Josephine Galatioto, Cristina I Caescu, Pauline Arnaud, Rhodora C Calizo, Bart Spronck, Sae-Il Murtada, Roshan Borkar, Alan Weinberg, Evren U Azeloglu, Maria Bintanel-Morcillo, James M Gallo, Jay D Humphrey, Guillaume Jondeau, Catherine Boileau, Francesco Ramirez, Ravi Iyengar
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 Spherical equivalent (joint main effects and education interaction). The EFO term self reported educational attainment, refractive error 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:
Q Fan, VJ Verhoeven, R Wojciechowski, VA Barathi, PG Hysi, JA Guggenheim, R Höhn, V Vitart, AP Khawaja, K Yamashiro, SM Hosseini, T Lehtimäki, Y Lu, T Haller, J Xie, C Delcourt, M Pirastu, J Wedenoja, P Gharahkhani, C Venturini, M Miyake, AW Hewitt, X Guo, J Mazur, JE Huffman, KM Williams, O Polasek, H Campbell, I Rudan, Z Vatavuk, JF Wilson, PK Joshi, G McMahon, B St Pourcain, DM Evans, CL Simpson, TH Schwantes-An, RP Igo, A Mirshahi, A Cougnard-Gregoire, C Bellenguez, M Blettner, O Raitakari, M Kähönen, I Seppala, T Zeller, T Meitinger, JS Ried, C Gieger, L Portas, EM van Leeuwen, N Amin, AG Uitterlinden, F Rivadeneira, A Hofman, JR Vingerling, YX Wang, X Wang, E Tai-Hui Boh, MK Ikram, C Sabanayagam, P Gupta, V Tan, L Zhou, CE Ho, W Lim, RW Beuerman, R Siantar, ES Tai, E Vithana, E Mihailov, CC Khor, C Hayward, RN Luben, PJ Foster, BE Klein, R Klein, HS Wong, P Mitchell, A Metspalu, T Aung, TL Young, M He, O Pärssinen, CM van Duijn, J Jin Wang, C Williams, JB Jonas, YY Teo, DA Mackey, K Oexle, N Yoshimura, AD Paterson, N Pfeiffer, TY Wong, PN Baird, D Stambolian, JE Wilson, CY Cheng, CJ Hammond, CC Klaver, SM Saw, JS Rahi, JF Korobelnik, JP Kemp, NJ Timpson, GD Smith, JE Craig, KP Burdon, RD Fogarty, SK Iyengar, E Chew, S Janmahasatian, NG Martin, S MacGregor, L Xu, M Schache, V Nangia, S Panda-Jonas, AF Wright, JR Fondran, JH Lass, S Feng, JH Zhao, KT Khaw, NJ Wareham, T Rantanen, J Kaprio, CP Pang, LJ Chen, PO Tam, V Jhanji, AL Young, A Döring, LJ Raffel, MF Cotch, X Li, SP Yip, MK Yap, G Biino, S Vaccargiu, M Fossarello, B Fleck, S Yazar, JW Tideman, M Tedja, MM Deangelis, M Morrison, L Farrer, X Zhou, W Chen, N Mizuki, A Meguro, KM Mäkelä
Upregulated genes from TAA tissues of Fbn1(mgR/mgR) MFS male mice compared to WT at P16
Description:
Throracic Aortic Aneurysms (TAAs) are a major clinical feature of Marfan syndrome (MFS). It is associated with mutations in the MFN1 gene encoding the multifunctional extracellular matrix glycoprotein Fibrillin-1. TAAs are life-threatening pathologies characterized by progressive vessel dilations associated with smooth muscle (SMC) dysfunction, occasional localiized inflammatory infiltrates, and severe maladaptive extracellular matrix (ECM) remodelling that, together, predispose the arterial wall to dissection and rupture leading to premature death. For this geneset expression values were obtained from the GEO accession GSE128101, and the corresponding SRA study accession SRP188087. The control GEO sample accessions were GSM3673486, GSM3673487 and GSM3673488 (corresponding in the SRA to SRX5527666, SRX5527667 & SRX5527668) compared to the case GEO sample accessions GSM3673483, GSM3673484 and GSM3673485 (corresponding to SRA accessions SRX5527663, SRX552764 & SRX552765). 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 log base 2 of the fold change are presented with a FDR of <0.05. All ensembl gene ids were checked in MGI for duplicates. The strain background was C57BL/6J, and all mice were male and sacrificed at P16.
Authors:
Jens Hansen, Josephine Galatioto, Cristina I Caescu, Pauline Arnaud, Rhodora C Calizo, Bart Spronck, Sae-Il Murtada, Roshan Borkar, Alan Weinberg, Evren U Azeloglu, Maria Bintanel-Morcillo, James M Gallo, Jay D Humphrey, Guillaume Jondeau, Catherine Boileau, Francesco Ramirez, Ravi Iyengar
Chromosome 15 yielded consistent evidence of linkage across the samples (Fig. 2), with a maximum lod score of 2.0 in the combined sample between markersD15S143 (15:47903311-47903423) and GATA153 (GATA153f11 15:57434446-57434649) which are 8 cM apart. Factor two explains 14% of the variance and is loaded such that higher values reflect a later age of onset of drinking, higher harm avoidance and lower novelty seeking.
Authors:
Dick DM, Nurnberger J Jr, Edenberg HJ, Goate A, Crowe R, Rice J, Bucholz KK, Kramer J, Schuckit MA, Smith TL, Porjesz B, Begleiter H, Hesselbrock V, Foroud T
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
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
DEG methadone human cortical organoids cell line B_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 B_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
Whole Brain Gene Expression Correlates for ACTI_DIFF_20 measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTI_DIFF_20 measures Difference in distance traveled (cm) during the first last min (saline-ethanol) 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
Whole Brain Gene Expression Correlates for ACTITOT_DIFF measured in BXD RI Males obtained using INIA Brain mRNA M430 (Jun06) RMA. The ACTITOT_DIFF measures Difference in total distance traveled (cm) (saline-ethanol) 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
Hippocampus Gene Expression Correlates for LM_ALT_CONTEXT measured in BXD RI Males obtained using GeneNetwork Hippocampus Consortium M430v2 (Jun06) RMA. The LM_ALT_CONTEXT measures Activity in altered context in fear conditioning apparatus 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
Striatum Gene Expression Correlates for MDMA_ACT_SAL_2 measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The MDMA_ACT_SAL_2 measures Locomotor activity after second saline treatment. under the domain MDMA. 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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