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.
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 Psychosis in Alzheimer's disease. The EFO term Alzheimers disease, psychotic symptoms 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:
P Hollingworth, R Sweet, R Sims, D Harold, G Russo, R Abraham, A Stretton, N Jones, A Gerrish, J Chapman, D Ivanov, V Moskvina, S Lovestone, P Priotsi, M Lupton, C Brayne, M Gill, B Lawlor, A Lynch, D Craig, B McGuinness, J Johnston, C Holmes, G Livingston, NJ Bass, H Gurling, A McQuillin, P Holmans, L Jones, B Devlin, L Klei, MM Barmada, FY Demirci, ST DeKosky, OL Lopez, P Passmore, MJ Owen, MC O'Donovan, R Mayeux, MI Kamboh, J Williams
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 Alzheimer's disease (late onset). The EFO term Alzheimers 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:
AC Naj, G Jun, GW Beecham, LS Wang, BN Vardarajan, J Buros, PJ Gallins, JD Buxbaum, GP Jarvik, PK Crane, EB Larson, TD Bird, BF Boeve, NR Graff-Radford, PL De Jager, D Evans, JA Schneider, MM Carrasquillo, N Ertekin-Taner, SG Younkin, C Cruchaga, JS Kauwe, P Nowotny, P Kramer, J Hardy, MJ Huentelman, AJ Myers, MM Barmada, FY Demirci, CT Baldwin, RC Green, E Rogaeva, P St George-Hyslop, SE Arnold, R Barber, T Beach, EH Bigio, JD Bowen, A Boxer, JR Burke, NJ Cairns, CS Carlson, RM Carney, SL Carroll, HC Chui, DG Clark, J Corneveaux, CW Cotman, JL Cummings, C DeCarli, ST DeKosky, R Diaz-Arrastia, M Dick, DW Dickson, WG Ellis, KM Faber, KB Fallon, MR Farlow, S Ferris, MP Frosch, DR Galasko, M Ganguli, M Gearing, DH Geschwind, B Ghetti, JR Gilbert, S Gilman, B Giordani, JD Glass, JH Growdon, RL Hamilton, LE Harrell, E Head, LS Honig, CM Hulette, BT Hyman, GA Jicha, LW Jin, N Johnson, J Karlawish, A Karydas, JA Kaye, R Kim, EH Koo, NW Kowall, JJ Lah, AI Levey, AP Lieberman, OL Lopez, WJ Mack, DC Marson, F Martiniuk, DC Mash, E Masliah, WC McCormick, SM McCurry, AN McDavid, AC McKee, M Mesulam, BL Miller, CA Miller, JW Miller, JE Parisi, DP Perl, E Peskind, RC Petersen, WW Poon, JF Quinn, RA Rajbhandary, M Raskind, B Reisberg, JM Ringman, ED Roberson, RN Rosenberg, M Sano, LS Schneider, W Seeley, ML Shelanski, MA Slifer, CD Smith, JA Sonnen, S Spina, RA Stern, RE Tanzi, JQ Trojanowski, JC Troncoso, VM Van Deerlin, HV Vinters, JP Vonsattel, S Weintraub, KA Welsh-Bohmer, J Williamson, RL Woltjer, LB Cantwell, BA Dombroski, D Beekly, KL Lunetta, ER Martin, MI Kamboh, AJ Saykin, EM Reiman, DA Bennett, JC Morris, TJ Montine, AM Goate, D Blacker, DW Tsuang, H Hakonarson, WA Kukull, TM Foroud, JL Haines, R Mayeux, MA Pericak-Vance, LA Farrer, GD Schellenberg
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 Tourette syndrome. The EFO term Tourette syndrome 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:
JM Scharf, D Yu, CA Mathews, BM Neale, SE Stewart, JA Fagerness, P Evans, E Gamazon, CK Edlund, SK Service, A Tikhomirov, L Osiecki, C Illmann, A Pluzhnikov, A Konkashbaev, LK Davis, B Han, J Crane, P Moorjani, AT Crenshaw, MA Parkin, VI Reus, TL Lowe, M Rangel-Lugo, S Chouinard, Y Dion, S Girard, DC Cath, JH Smit, RA King, TV Fernandez, JF Leckman, KK Kidd, JR Kidd, AJ Pakstis, MW State, LD Herrera, R Romero, E Fournier, P Sandor, CL Barr, N Phan, V Gross-Tsur, F Benarroch, Y Pollak, CL Budman, RD Bruun, G Erenberg, AL Naarden, PC Lee, N Weiss, B Kremeyer, GB Berrío, DD Campbell, JC Cardona Silgado, WC Ochoa, SC Mesa Restrepo, H Muller, AV Valencia Duarte, GJ Lyon, M Leppert, J Morgan, R Weiss, MA Grados, K Anderson, S Davarya, H Singer, J Walkup, J Jankovic, JA Tischfield, GA Heiman, DL Gilbert, PJ Hoekstra, MM Robertson, R Kurlan, C Liu, JR Gibbs, A Singleton, J Hardy, E Strengman, RA Ophoff, M Wagner, R Moessner, DB Mirel, D Posthuma, C Sabatti, E Eskin, DV Conti, JA Knowles, A Ruiz-Linares, GA Rouleau, S Purcell, P Heutink, BA Oostra, WM McMahon, NB Freimer, NJ Cox, DL Pauls
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 Alzheimer's disease in APOE e4- carriers. The EFO term Alzheimers 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:
G Jun, CA Ibrahim-Verbaas, M Vronskaya, JC Lambert, J Chung, AC Naj, BW Kunkle, LS Wang, JC Bis, C Bellenguez, D Harold, KL Lunetta, AL Destefano, B Grenier-Boley, R Sims, GW Beecham, AV Smith, V Chouraki, KL Hamilton-Nelson, MA Ikram, N Fievet, N Denning, ER Martin, H Schmidt, Y Kamatani, ML Dunstan, O Valladares, AR Laza, D Zelenika, A Ramirez, TM Foroud, SH Choi, A Boland, T Becker, WA Kukull, SJ van der Lee, F Pasquier, C Cruchaga, D Beekly, AL Fitzpatrick, O Hanon, M Gill, R Barber, V Gudnason, D Campion, S Love, DA Bennett, N Amin, C Berr, M Tsolaki, JD Buxbaum, OL Lopez, V Deramecourt, NC Fox, LB Cantwell, L Tárraga, C Dufouil, J Hardy, PK Crane, G Eiriksdottir, D Hannequin, R Clarke, D Evans, TH Mosley, L Letenneur, C Brayne, W Maier, P De Jager, V Emilsson, JF Dartigues, H Hampel, MI Kamboh, RF de Bruijn, C Tzourio, P Pastor, EB Larson, JI Rotter, MC O'Donovan, TJ Montine, MA Nalls, S Mead, EM Reiman, PV Jonsson, C Holmes, PH St George-Hyslop, M Boada, P Passmore, JR Wendland, R Schmidt, K Morgan, AR Winslow, JF Powell, M Carasquillo, SG Younkin, J Jakobsdóttir, JS Kauwe, KC Wilhelmsen, D Rujescu, MM Nöthen, A Hofman, L Jones, JL Haines, BM Psaty, C Van Broeckhoven, P Holmans, LJ Launer, R Mayeux, M Lathrop, AM Goate, V Escott-Price, S Seshadri, MA Pericak-Vance, P Amouyel, J Williams, CM van Duijn, GD Schellenberg, LA Farrer
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 Alzheimer's disease. The EFO term Alzheimers 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:
C Antúnez, M Boada, A González-Pérez, J Gayán, R Ramírez-Lorca, J Marín, I Hernández, C Moreno-Rey, FJ Morón, J López-Arrieta, A Mauleón, M Rosende-Roca, F Noguera-Perea, A Legaz-García, L Vivancos-Moreau, J Velasco, JM Carrasco, M Alegret, M Antequera-Torres, S Manzanares, A Romo, I Blanca, S Ruiz, A Espinosa, S Castaño, B García, B Martínez-Herrada, G Vinyes, A Lafuente, JT Becker, JJ Galán, M Serrano-Ríos, E Vázquez, L Tárraga, ME Sáez, OL López, LM Real, A Ruiz
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 Alzheimer's disease. The EFO term Alzheimers 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:
D Harold, R Abraham, P Hollingworth, R Sims, A Gerrish, ML Hamshere, JS Pahwa, V Moskvina, K Dowzell, A Williams, N Jones, C Thomas, A Stretton, AR Morgan, S Lovestone, J Powell, P Proitsi, MK Lupton, C Brayne, DC Rubinsztein, M Gill, B Lawlor, A Lynch, K Morgan, KS Brown, PA Passmore, D Craig, B McGuinness, S Todd, C Holmes, D Mann, AD Smith, S Love, PG Kehoe, J Hardy, S Mead, N Fox, M Rossor, J Collinge, W Maier, F Jessen, B Schürmann, R Heun, H van den Bussche, I Heuser, J Kornhuber, J Wiltfang, M Dichgans, L Frölich, H Hampel, M Hüll, D Rujescu, AM Goate, JS Kauwe, C Cruchaga, P Nowotny, JC Morris, K Mayo, K Sleegers, K Bettens, S Engelborghs, PP De Deyn, C Van Broeckhoven, G Livingston, NJ Bass, H Gurling, A McQuillin, R Gwilliam, P Deloukas, A Al-Chalabi, CE Shaw, M Tsolaki, AB Singleton, R Guerreiro, TW Mühleisen, MM Nöthen, S Moebus, KH Jöckel, N Klopp, HE Wichmann, MM Carrasquillo, VS Pankratz, SG Younkin, PA Holmans, M O'Donovan, MJ Owen, J Williams
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 Alzheimer's disease (late onset). The EFO term Alzheimers 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:
JC Lambert, CA Ibrahim-Verbaas, D Harold, AC Naj, R Sims, C Bellenguez, AL DeStafano, JC Bis, GW Beecham, B Grenier-Boley, G Russo, TA Thorton-Wells, N Jones, AV Smith, V Chouraki, C Thomas, MA Ikram, D Zelenika, BN Vardarajan, Y Kamatani, CF Lin, A Gerrish, H Schmidt, B Kunkle, ML Dunstan, A Ruiz, MT Bihoreau, SH Choi, C Reitz, F Pasquier, C Cruchaga, D Craig, N Amin, C Berr, OL Lopez, PL De Jager, V Deramecourt, JA Johnston, D Evans, S Lovestone, L Letenneur, FJ Morón, DC Rubinsztein, G Eiriksdottir, K Sleegers, AM Goate, N Fiévet, MW Huentelman, M Gill, K Brown, MI Kamboh, L Keller, P Barberger-Gateau, B McGuiness, EB Larson, R Green, AJ Myers, C Dufouil, S Todd, D Wallon, S Love, E Rogaeva, J Gallacher, P St George-Hyslop, J Clarimon, A Lleo, A Bayer, DW Tsuang, L Yu, M Tsolaki, P Bossù, G Spalletta, P Proitsi, J Collinge, S Sorbi, F Sanchez-Garcia, NC Fox, J Hardy, MC Deniz Naranjo, P Bosco, R Clarke, C Brayne, D Galimberti, M Mancuso, F Matthews, S Moebus, P Mecocci, M Del Zompo, W Maier, H Hampel, A Pilotto, M Bullido, F Panza, P Caffarra, B Nacmias, JR Gilbert, M Mayhaus, L Lannefelt, H Hakonarson, S Pichler, MM Carrasquillo, M Ingelsson, D Beekly, V Alvarez, F Zou, O Valladares, SG Younkin, E Coto, KL Hamilton-Nelson, W Gu, C Razquin, P Pastor, I Mateo, MJ Owen, KM Faber, PV Jonsson, O Combarros, MC O'Donovan, LB Cantwell, H Soininen, D Blacker, S Mead, TH Mosley, DA Bennett, TB Harris, L Fratiglioni, C Holmes, RF de Bruijn, P Passmore, TJ Montine, K Bettens, JI Rotter, A Brice, K Morgan, TM Foroud, WA Kukull, D Hannequin, JF Powell, MA Nalls, K Ritchie, KL Lunetta, JS Kauwe, E Boerwinkle, M Riemenschneider, M Boada, M Hiltuenen, ER Martin, R Schmidt, D Rujescu, LS Wang, JF Dartigues, R Mayeux, C Tzourio, A Hofman, MM Nöthen, C Graff, BM Psaty, L Jones, JL Haines, PA Holmans, M Lathrop, MA Pericak-Vance, LJ Launer, LA Farrer, CM van Duijn, C Van Broeckhoven, V Moskvina, S Seshadri, J Williams, GD Schellenberg, P Amouyel
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