Search

Your search keyword '"Biederer, Thomas"' showing total 267 results
Start Over Author "Biederer, Thomas"
267 results on '"Biederer, Thomas"'

1. CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice

Author

Sanchez-Roige, Sandra, Jennings, Mariela V, Thorpe, Hayley HA, Mallari, Jazlene E, van der Werf, Lieke C, Bianchi, Sevim B, Huang, Yuye, Lee, Calvin, Mallard, Travis T, Barnes, Samuel A, Wu, Jin Yi, Barkley-Levenson, Amanda M, Boussaty, Ely C, Snethlage, Cedric E, Schafer, Danielle, Babic, Zeljana, Winters, Boyer D, Watters, Katherine E, Biederer, Thomas, Mackillop, James, Stephens, David N, Elson, Sarah L, Fontanillas, Pierre, Khokhar, Jibran Y, Young, Jared W, and Palmer, Abraham A

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Social and Personality Psychology, Psychology, Pharmacology and Pharmaceutical Sciences, Behavioral and Social Science, Clinical Research, Mental Health, Human Genome, Substance Misuse, Drug Abuse (NIDA only), Genetics, Basic Behavioral and Social Science, Brain Disorders, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Good Health and Well Being, Humans, Animals, Mice, Genome-Wide Association Study, Phenotype, Impulsive Behavior, Substance-Related Disorders, Personality, Polymorphism, Single Nucleotide, Cell Adhesion Molecules, 23andMe Research Team, Clinical Sciences, Public Health and Health Services, Clinical sciences, Neurosciences, Biological psychology
Abstract

Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale (N = 123,509-133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation (N = 130,684). Because these GWAS implicated the gene CADM2, we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort (N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS ("MouseWAS") by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6-11%), and moderate genetic correlations (rg = 0.20-0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF, and also identified nominal associations proximal to DRD2 and CRHR1. PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

Published
2023

2. 69. CADM2 IS IMPLICATED IN IMPULSIVE PERSONALITY AND NUMEROUS OTHER TRAITS BY GENOME- AND PHENOME-WIDE ASSOCIATION STUDIES IN HUMANS, WITH FURTHER SUPPORT FROM STUDIES OF CADM2 MUTANT MICE

Author

Sanchez-Roige, Sandra, Jennings, Mariela V, Thorpe, Hayley HA, Mallari, Jazlene, van der Werf, Lieke C, Bianchi, Sevim B, Mallard, Travis T, Watters, Katherine E, Biederer, Thomas, Team, 23andMe Research, Elson, Sarah L, Fontanillas, Pierre, Khokhar, Jibran Y, Young, Jared W, and Palmer, Abraham A

Subjects
Biological Psychology, Psychology, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Neurosciences, Biological psychology
Published
2022

5. Three-dimensional adaptive optical nanoscopy for thick specimen imaging at sub-50-nm resolution

Author

Hao, Xiang, Allgeyer, Edward S, Lee, Dong-Ryoung, Antonello, Jacopo, Watters, Katherine, Gerdes, Julianne A, Schroeder, Lena K, Bottanelli, Francesca, Zhao, Jiaxi, Kidd, Phylicia, Lessard, Mark D, Rothman, James E, Cooley, Lynn, Biederer, Thomas, Booth, Martin J, and Bewersdorf, Joerg

Subjects
Biological Sciences, Bioengineering, Imaging, Three-Dimensional, Microscopy, Fluorescence, Nanotechnology, Optics and Photonics, Signal-To-Noise Ratio, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

Understanding cellular organization demands the best possible spatial resolution in all three dimensions. In fluorescence microscopy, this is achieved by 4Pi nanoscopy methods that combine the concepts of using two opposing objectives for optimal diffraction-limited 3D resolution with switching fluorescent molecules between bright and dark states to break the diffraction limit. However, optical aberrations have limited these nanoscopes to thin samples and prevented their application in thick specimens. Here we have developed an improved iso-stimulated emission depletion nanoscope, which uses an advanced adaptive optics strategy to achieve sub-50-nm isotropic resolution of structures such as neuronal synapses and ring canals previously inaccessible in tissue. The adaptive optics scheme presented in this work is generally applicable to any microscope with a similar beam path geometry involving two opposing objectives to optimize resolution when imaging deep in aberrating specimens.

Published
2021

6. A synaptomic analysis reveals dopamine hub synapses in the mouse striatum

Author

Paget-Blanc, Vincent, Pfeffer, Marlene E., Pronot, Marie, Lapios, Paul, Angelo, Maria-Florencia, Walle, Roman, Cordelières, Fabrice P., Levet, Florian, Claverol, Stéphane, Lacomme, Sabrina, Petrel, Mélina, Martin, Christelle, Pitard, Vincent, De Smedt Peyrusse, Véronique, Biederer, Thomas, Perrais, David, Trifilieff, Pierre, and Herzog, Etienne

Published
2022
Full Text
View/download PDF

7. Transient Impairment in Microglial Function Causes Sex-Specific Deficits in Synaptic and Hippocampal Function in Mice Exposed to Early Adversity

Author

Ahmed, Sahabuddin, primary, Polis, Baruh, additional, Jamwal, Sumit, additional, Sanganahalli, Basavaraju G., additional, MacDowell Kaswan, Zoe, additional, Islam, Rafiad, additional, Kim, Dana, additional, Bowers, Christian, additional, Giuliano, Lauryn, additional, Biederer, Thomas, additional, Hyder, Fahmeed, additional, and Kaffman, Arie, additional

Published
2024
Full Text
View/download PDF

10. NeuroD2 regulates the development of hippocampal mossy fiber synapses

Author

Wilke, Scott A, Hall, Benjamin J, Antonios, Joseph K, DeNardo, Laura A, Otto, Stefanie, Yuan, Bo, Chen, Fading, Robbins, Elissa M, Tiglio, Katie, Williams, Megan E, Qiu, Zilong, Biederer, Thomas, and Ghosh, Anirvan

Abstract

Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF) synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Published
2012

14. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

Trubetskoy, Vassily, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Braun, Alice, Kraft, Julia, Skarabis, Nora, Walter, Henrik, Ripke, Stephan, Pardiñas, Antonio F., Dennison, Charlotte A., Hall, Lynsey S., Harwood, Janet C., Richards, Alexander L., Legge, Sophie E., Lynham, Amy, Williams, Nigel M., Bray, Nicholas J., Escott-Price, Valentina, Kirov, George, Holmans, Peter A., Pocklington, Andrew J., Owen, Michael J., Walters, James T. R., O’Donovan, Michael C., Qi, Ting, Sidorenko, Julia, Wu, Yang, Zeng, Jian, Gratten, Jacob, Visscher, Peter M., Yang, Jian, Wray, Naomi R., Bigdeli, Tim B., Fanous, Ayman H., Bryois, Julien, Bergen, Sarah E., Kähler, Anna K., Magnusson, Patrik K. E., Hultman, Christina M., Sullivan, Patrick F., Chen, Chia-Yen, Atkinson, Elizabeth G., Goldstein, Jacqueline I., Howrigan, Daniel P., Martin, Alicia R., Daly, Mark J., Huang, Hailiang, Neale, Benjamin M., Ge, Tian, Lam, Max, Belliveau, Richard A., Chambert, Kimberley D., Genovese, Giulio, Lee, Phil H., Pietiläinen, Olli, McCarroll, Steven A., Moran, Jennifer L., Smoller, Jordan W., Brown, Tyler C., Feng, Guoping, Hyman, Steven E., Sheng, Morgan, Chong, Siow Ann, Subramaniam, Mythily, Lencz, Todd, Malhotra, Anil K., Watanabe, Kyoko, Frei, Oleksandr, Agartz, Ingrid, Athanasiu, Lavinia, Melle, Ingrid, Andreassen, Ole A., Steen, Nils Eiel, DeLisi, Lynn E., Mesholam-Gately, Raquelle I., Seidman, Larry J., Koopmans, Frank, Magnusson, Sigurdur, Stefánsson, Hreinn, Stefansson, Kari, Grove, Jakob, Agerbo, Esben, Als, Thomas D., Bybjerg-Grauholm, Jonas, Demontis, Ditte, Hougaard, David M., Mors, Ole, Mortensen, Preben B., Nordentoft, Merete, Børglum, Anders D., Mattheisen, Manuel, Kim, Minsoo, Gandal, Michael J., Li, Zhiqiang, Shi, Yongyong, Zhou, Wei, Qin, Shengying, Voloudakis, Georgios, Zhang, Wen, Roussos, Panos, Adams, Mark, McIntosh, Andrew, Söderman, Erik, Jönsson, Erik G., McGrath, John J., Al Eissa, Mariam, Bass, Nicholas J., Fiorentino, Alessia, O’Brien, Niamh Louise, Pimm, Jonathan, Sharp, Sally Isabel, McQuillin, Andrew, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z., Bruggeman, Richard, Alptekin, Köksal, Amin, Farooq, Arolt, Volker, Lencer, Rebecca, Rothermundt, Matthias, Baune, Bernhard T., Arrojo, Manuel, Azevedo, Maria Helena, Bacanu, Silviu A., Webb, Bradley T., Wormley, Brandon K., Riley, Brien P., Kendler, Kenneth S., Begemann, Martin, Mitjans, Marina, Steixner-Kumar, Agnes A., Ehrenreich, Hannelore, Bene, Judit, Benyamin, Beben, Blasi, Giuseppe, Rampino, Antonio, Torretta, Silvia, Bertolino, Alessandro, Bobes, Julio, Bonassi, Stefano, Bressan, Rodrigo Affonseca, Gadelha, Ary, Noto, Cristiano, Ota, Vanessa Kiyomi, Santoro, Marcos Leite, Belangero, Sintia Iole, Bromet, Evelyn J., Buckley, Peter F., Buckner, Randy L., Cahn, Wiepke, Kahn, René S., Cairns, Murray J., Scott, Rodney J., Tooney, Paul A., Schall, Ulrich, Calkins, Monica E., Gur, Raquel E., Gur, Ruben C., Turetsky, Bruce I., Carr, Vaughan J., Castle, David, Harvey, Carol, Catts, Stanley V., Chan, Raymond C. K., Chaumette, Boris, Kebir, Oussama, Krebs, Marie-Odile, Cheng, Wei, Cheung, Eric F. C., Cohen, David, Consoli, Angèle, Giannitelli, Marianna, Laurent-Levinson, Claudine, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Quattrone, Diego, Breen, Gerome, Collier, David A., Di Forti, Marta, Vassos, Evangelos, Mondelli, Valeria, van Amelsvoort, Therese, Murray, Robin M., Davidson, Michael, Davis, Kenneth L., Haroutunian, Vahram, Malaspina, Dolores, Reichenberg, Abraham, Siever, Larry J., Silverman, Jeremy M., Buxbaum, Joseph D., de Haan, Lieuwe, Degenhardt, Franziska, Forstner, Andreas, Nöthen, Markus M., Dickerson, Faith, Dikeos, Dimitris, Papadimitriou, George N., Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Gejman, Pablo V., Sanders, Alan R., Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G., Fañanás, Lourdes, Peñas, Javier González, González-Pinto, Ana, Molto, María Dolores, Moreno, Carmen, Parellada, Mara, Sanjuan, Julio, Crepo-Facorro, Benedicto, Mata, Ignacio, Arango, Celso, Faraone, Stephen V., Frank, Josef, Streit, Fabian, Witt, Stephanie H., Rietschel, Marcella, Freimer, Nelson B., Ophoff, Roel A., Fromer, Menachem, Stahl, Eli A., Frustaci, Alessandra, Gershon, Elliot S., Giegling, Ina, Hartmann, Annette M., Konte, Bettina, Rujescu, Dan, Giusti-Rodríguez, Paola, Szatkiewicz, Jin P., Godard, Stephanie, González Peñas, Javier, Gopal, Srihari, Savitz, Adam, Li, Qingqin S., Green, Michael F., Nuechterlein, Keith H., Sugar, Catherine A., Greenwood, Tiffany A., Light, Gregory A., Swerdlow, Neal R., Braff, David, Guillin, Olivier, Campion, Dominique, Gülöksüz, Sinan, Luykx, Jurjen J., Rutten, Bart P. F., van Winkel, Ruud, Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Pellegrino, Renata, Pantelis, Christos, Hayward, Caroline, Henskens, Frans A., Kelly, Brian J., Herms, Stefan, Hoffmann, Per, Ikeda, Masashi, Iwata, Nakao, Iyegbe, Conrad, van Os, Jim, Joa, Inge, Julià, Antonio, Marsal, Sara, Kam-Thong, Tony, Rautanen, Anna, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Toncheva, Draga, Keller, Matthew C., Khrunin, Andrey, Limborska, Svetlana, Slominsky, Petr, Kim, Sung-Wan, Klovins, Janis, Nikitina-Zake, Liene, Kondratiev, Nikolay, Golimbet, Vera, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C., Levinson, Douglas F., Petryshen, Tracey L., Lehrer, Douglas S., Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Stroup, T. Scott, Liu, Chih-Min, Hwu, Hai-Gwo, Lönnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Bakker, Steven, Kahn, René, Macek, Milan, Mackinnon, Andrew, Maher, Brion S., Maier, Wolfgang, Atbaşoğlu, Eşref Cem, Mallet, Jacques, Marder, Stephen R., Martorell, Lourdes, Muntané, Gerard, Vilella, Elisabet, Meier, Sandra, Schulze, Thomas G., McCarley, Robert W., McDonald, Colm, Donohoe, Gary, Morris, Derek W., Periyasamy, Sathish, Mowry, Bryan J., Medeiros, Helena, Sobell, Janet L., Melegh, Bela, Metspalu, Andres, Milani, Lili, Esko, Tõnu, Michie, Patricia T., Milanova, Vihra, Molden, Espen, Molina, Esther, Morley, Christopher P., Murphy, Kieran C., Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Pulver, Ann E., O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Freedman, Robert, Paunio, Tiina, Perkins, Diana O., Pfuhlmann, Bruno, Benner, Christian, Pirinen, Matti, Palotie, Aarno, Porteous, David, Powell, John, Quested, Digby, Radant, Allen D., Tsuang, Debby W., Rapaport, Mark H., Roe, Cheryl, Liu, Chunyu, Roffman, Joshua L., Roth, Julian, Gawlik, Micha, Saker-Delye, Safaa, Salomaa, Veikko, Suvisaari, Jaana, Shi, Jianxin, Sigurdsson, Engilbert, Sim, Kang, So, Hon-Cheong, Stain, Helen J., Stögmann, Elisabeth, Zimprich, Fritz, Stone, William S., Straub, Richard E., Hyde, Thomas, Jaffe, Andrew, Weinberger, Daniel R., Strengman, Eric, Svrakic, Dragan M., Cloninger, C. Robert, Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Tosato, Sarah, Tura, Gian Battista, Üçok, Alp, Vaaler, Arne, Veijola, Juha, Waddington, John, Waterreus, Anna, Morgan, Vera A., Jablensky, Assen V., Weiser, Mark, Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C., Kennedy, James L., Zhu, Feng, Saka, Meram C., Ayub, Muhammad, Black, Donald W., Buccola, Nancy G., Byerley, William F., Chen, Wei J., Crespo-Facorro, Benedicto, Galletly, Cherrie, Gennarelli, Massimo, Müller-Myhsok, Bertram, Neil, Amanda L., Pato, Michele T., Pato, Carlos N., Wang, Shi-Heng, Xu, Shuhua, Adolfsson, Rolf, Bramon, Elvira, Cervilla, Jorge A., Cichon, Sven, Corvin, Aiden, Gill, Michael, Curtis, David, Domenici, Enrico, Gareeva, Anna, Khusnutdinova, Elza, Glatt, Stephen J., Hong, Kyung Sue, Knowles, James A., Lee, Jimmy, Liu, Jianjun, Malhotra, Dheeraj, Menezes, Paulo R., Nimgaonkar, Vishwajit, Paciga, Sara A., Rivera, Margarita, Schwab, Sibylle G., Serretti, Alessandro, Sham, Pak C., Clair, David St, Tsuang, Ming T., Vawter, Marquis P., Werge, Thomas, Wildenauer, Dieter B., Yu, Xin, Yue, Weihua, Verhage, Matthijs, Sahasrabudhe, Dnyanada, Toonen, Ruud F., Posthuma, Danielle, Dai, Nan, Wenwen, Qin, Wildenauer, D. B., Agiananda, Feranindhya, Amir, Nurmiati, Antoni, Ronald, Arsianti, Tiana, Asmarahadi, Asmarahadi, Diatri, H., Djatmiko, Prianto, Irmansyah, Irmansyah, Khalimah, Siti, Kusumadewi, Irmia, Kusumaningrum, Profitasari, Lukman, Petrin R., Nasrun, Martina W., Safyuni, N. S., Prasetyawan, Prasetyawan, Semen, G., Siste, Kristiana, Tobing, Heriani, Widiasih, Natalia, Wiguna, Tjhin, Wulandari, D., Evalina, None, Hananto, A. J., Ismoyo, Joni H., Marini, T. M., Henuhili, Supiyani, Reza, Muhammad, Yusnadewi, Suzy, Abyzov, Alexej, Akbarian, Schahram, van Bakel, Harm, Breen, Michael, Charney, Alex, Dracheva, Stella, Girdhar, Kiran, Hoffman, Gabriel, Jiang, Yan, Pinto, Dalila, Purcell, Shaun, Roussos, Panagiotis, Wiseman, Jennifer, Ashley-Koch, Allison, Crawford, Gregory, Reddy, Tim, Brown, Miguel, Grennan, Kay, Carlyle, Becky, Emani, Prashant, Galeev, Timur, Gerstein, Mark, Gu, Mengting, Guerra, Brittney, Gursoy, Gamze, Kitchen, Robert, Lee, Donghoon, Li, Mingfeng, Liu, Shuang, Navarro, Fabio, Pan, Xinghua, Pochareddy, Sirisha, Rozowsky, Joel, Sestan, Nenad, Sethi, Anurag, Shi, Xu, Szekely, Anna, Wang, Daifeng, Warrell, Jonathan, Weissman, Sherman, Wu, Feinan, Xu, Xuming, Coetzee, Gerard, Farnham, Peggy, Lay, Fides, Rhie, Suhn, Witt, Heather, Wood, Shannon, Yao, Lijing, Gandal, Mike, Polioudakis, Damon, Swarup, Vivek, Won, Hyejung, Giase, Gina, Jiang, Shan, Kefi, Amira, Shieh, Annie, Goes, Fernando, Zandi, Peter, Kim, Yunjung, Mattei, Eugenio, Purcaro, Michael, Pratt, Henry, Peters, Mette A., Sanders, Stephan, Weng, Zhiping, White, Kevin, Arranz, Maria J., Lewis, Cathryn, Lin, Kuang, Walshe, Muriel, Bender, Stephan, Weisbrod, Matthias, Hall, Jeremy, Lawrie, Stephen, Linszen, Don H., Achsel, Tilmann, Bagni, Claudia, Andres-Alonso, Maria, Kreutz, Michael R., Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Coba, Marcelo P., Cornelisse, L. Niels, van Weering, Jan R. T., de Jong, Arthur P. H., MacGillavry, Harold D., de Juan-Sanz, Jaime, Dieterich, Daniela C., Pielot, Rainer, Smalla, Karl-Heinz, Gundelfinger, Eckart D., Goldschmidt, Hana L., Huganir, Richard L., Hoogenraad, Casper, Imig, Cordelia, Jahn, Reinhard, Jung, Hwajin, Kim, Eunjoon, Kaeser, Pascal S., Lipstein, Noa, Malenka, Robert, McPherson, Peter S., O’Connor, Vincent, Ryan, Timothy A., Sala, Carlo, Verpelli, Chiara, Smit, August B., Südhof, Thomas C., Thomas, Paul D., Medical Research Council (UK), National Natural Science Foundation of China, Royal Society (UK), Chinese Academy of Sciences, Shanghai Science and Technology Committee, Research Council of Norway, European Commission, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Comunidad de Madrid, Fundación Alicia Koplowitz, Fundación Alonso Lozano, Mental Health Research UK, Wellcome Trust, Brain and Behavior Research Foundation, NIHR Biomedical Research Centre (UK), University College London, Generalitat Valenciana, Internal medicine, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), MUMC+: MA Med Staf Spec Psychiatrie (9), MUMC+: Hersen en Zenuw Centrum (3), Trubetskoy, Vassily, Pardiñas, Antonio F., Qi, Ting, Panagiotaropoulou, Georgia, Benyamin, Beben, O'Donovan, Michael C, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Molecular and Cellular Neurobiology, Functional Genomics, and Complex Trait Genetics

Subjects
Genetics of the nervous system, Schizophrenia/genetics, VARIANTS, PROFILE, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, DISEASE, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, Alleles, Genomics, Genome-Wide Association Study, Schizophrenia, Polymorphism, RISK, ARCHITECTURE, Science & Technology, Multidisciplinary, MUTATIONS, Genetic Predisposition to Disease/genetics, Settore BIO/13, Single Nucleotide, ASSOCIATION, Polymorphism, Single Nucleotide/genetics, STATISTICS, Multidisciplinary Sciences, INDIVIDUALS, Science & Technology - Other Topics, Diseases of the nervous system, ddc:500, Single Nucleotide/genetics, INTEGRATION
Abstract

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., The work at Cardiff University was additionally supported by Medical Research Council Centre grant no. MR/L010305/1 and program grant no. G0800509. S. Xu also gratefully acknowledges the support of the National Natural Science Foundation of China (NSFC) grants (31525014, 91731303, 31771388, 31961130380 and 32041008), the UK Royal Society-Newton Advanced Fellowship (NAF\R1\191094), the Key Research Program of Frontier Sciences (QYZDJ-SSW-SYS009) and the Strategic Priority Research Program (XDB38000000) of the Chinese Academy of Sciences, and the Shanghai Municipal Science and Technology Major Project (2017SHZDZX01). O. A. Andreassen was supported by the Research Council of Norway (283798, 262656, 248980, 273291, 248828, 248778, 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, EU H2020 no. 847776. B. Melegh was supported in part by the National Scientific Research Program (NKFIH) K 138669. S. V. Faraone is supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreements 667302 and 728018 and NIMH grants 5R01MH101519 and U01 MH109536-01. S. I. Belangero was supported by FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), grant numbers: 2010/08968-6; 2014/07280-1 2011/50740-5 (including R. A. Bressan). The Singapore team (J. Lee, J. Liu, K. Sim, S. A. Chong and M. Subramanian) acknowledges the National Medical Research Council Translational and Clinical Research Flagship Programme (grant no.: NMRC/TCR/003/2008). M. Macek was supported by LM2018132, CZ.02.1.01/0.0/0.0/18_046/0015515 and IP6003 –VZFNM00064203. C. Arango has been funded by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds, European Union Seventh Framework Program and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement no 115916, project PRISM; and grant agreement no. 777394, project AIMS-2-TRIALS), Fundación Familia Alonso and Fundación Alicia Koplowitz. E. Bramon acknowledges support from the National Institute of Health Research UK (grant NIHR200756); Mental Health Research UK John Grace QC Scholarship 2018; an ESRC collaborative award 2020; BMA Margaret Temple Fellowship 2016; Medical Research Council New Investigator Award (G0901310); MRC Centenary Award (G1100583); MRC project grant G1100583; National Institute of Health Research UK post-doctoral fellowship (PDA/02/06/016); NARSAD Young Investigator awards 2005 and 2008; Wellcome Trust Research Training Fellowship; Wellcome Trust Case Control Consortium awards (085475/B/08/Z, 085475/Z/08/Z); European Commission Horizon 2020 (747429); NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and King’s College London; and NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London (UCLH BRC - Mental Health Theme). D. Molto is funded by the European Regional Development Fund (ERDF)–Valencian Community 2014–2020, Spain. E. G. Atkinson was supported by the NIMH K01MH121659.

Published
2022

16. 69. CADM2 IS IMPLICATED IN IMPULSIVE PERSONALITY AND NUMEROUS OTHER TRAITS BY GENOME- AND PHENOME-WIDE ASSOCIATION STUDIES IN HUMANS, WITH FURTHER SUPPORT FROM STUDIES OF CADM2 MUTANT MICE

Author

Sanchez-Roige, Sandra, primary, Jennings, Mariela V, additional, Thorpe, Hayley HA, additional, Mallari, Jazlene, additional, van der Werf, Lieke C, additional, Bianchi, Sevim B, additional, Mallard, Travis T, additional, Watters, Katherine E, additional, Biederer, Thomas, additional, Elson, Sarah L, additional, Fontanillas, Pierre, additional, Khokhar, Jibran Y, additional, Young, Jared W, additional, and Palmer, Abraham A, additional

Published
2022
Full Text
View/download PDF

17. The human milk component myo-inositol promotes neuronal connectivity.

Author

Paquette, Andrew F., Carbone, Beatrice E., Vogel, Seth, Israel, Erica, Maria, Sarah D., Patil, Nikita P., Sah, Saroj, Chowdhury, Dhrubajyoti, Kondratiuk, Ilona, Labhart, Beau, Morrow, Ardythe L., Phillips, Shay C., Kuang, Chenzhong, Hondmann, Dirk, Pandey, Neeraj, and Biederer, Thomas

Subjects
BREAST milk, NEURAL development, DIETARY supplements, MILKFAT, FIREPROOFING agents, SYNAPSES, SYNAPTOGENESIS
Abstract

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo-inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. Myo-inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, myo-inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of myo-inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that myo-inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies myo-inositol as a breast milk component that promotes the formation of neuronal connections. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

18. Transcriptional diversity in specific synaptic gene sets discriminates cortical neuronal identity.

Author

Roig Adam, Amparo, Martínez-López, José A., van der Spek, Sophie J. F., The SYNGO consortium, Achsel, Tilmann, Andres-Alonso, Maria, Bagni, Claudia, Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Coba, Marcelo P., Cornelisse, L. Niels, de Juan-Sanz, Jaime, Goldschmidt, Hana L., Gundelfinger, Eckart D., Huganir, Richard L., Imig, Cordelia, Jahn, Reinhard, and Jung, Hwajin

Subjects
GENE expression, GENE regulatory networks, GENES, RNA sequencing, GENE ontology, PROTEOMICS
Abstract

Synapse diversity has been described from different perspectives, ranging from the specific neurotransmitters released, to their diverse biophysical properties and proteome profiles. However, synapse diversity at the transcriptional level has not been systematically identified across all synapse populations in the brain. To quantify and identify specific synaptic features of neuronal cell types we combined the SynGO (Synaptic Gene Ontology) database with single-cell RNA sequencing data of the mouse neocortex. We show that cell types can be discriminated by synaptic genes alone with the same power as all genes. The cell type discriminatory power is not equally distributed across synaptic genes as we could identify functional categories and synaptic compartments with greater cell type specific expression. Synaptic genes, and specific SynGO categories, belonged to three different types of gene modules: gradient expression over all cell types, gradient expression in selected cell types and cell class- or type-specific profiles. This data provides a deeper understanding of synapse diversity in the neocortex and identifies potential markers to selectively identify synapses from specific neuronal populations. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

22. All-optical visualization of specific molecules in the ultrastructural context of brain tissue

Author

M’Saad, Ons, primary, Kasula, Ravikiran, additional, Kondratiuk, Ilona, additional, Kidd, Phylicia, additional, Falahati, Hanieh, additional, Gentile, Juliana E., additional, Niescier, Robert F., additional, Watters, Katherine, additional, Sterner, Robert C., additional, Lee, Seong, additional, Liu, Xinran, additional, De Camilli, Pietro, additional, Rothman, James E., additional, Koleske, Anthony J., additional, Biederer, Thomas, additional, and Bewersdorf, Joerg, additional

Published
2022
Full Text
View/download PDF

25. CADM2is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice

Author

Sanchez-Roige, Sandra, primary, Jennings, Mariela V, additional, Thorpe, Hayley H A, additional, Mallari, Jazlene E, additional, van der Werf, Lieke C, additional, Bianchi, Sevim B, additional, Lee, Calvin, additional, Mallard, Travis T, additional, Barnes, Samuel A, additional, Wu, Jin Yi, additional, Barkley-Levenson, Amanda M, additional, Boussaty, Ely C, additional, Snethlage, Cedric E, additional, Schafer, Danielle, additional, Babic, Zeljana, additional, Winters, Boyer D, additional, Watters, Katherine E, additional, Biederer, Thomas, additional, Mackillop, James, additional, Stephens, David N, additional, Elson, Sarah L, additional, Fontanillas, Pierre, additional, Khokhar, Jibran Y, additional, Young, Jared W, additional, and Palmer, Abraham A, additional

Published
2022
Full Text
View/download PDF

28. L-histidine decarboxylase and Tourette's syndrome

Author

Ercan-Sencicek, A. Gulhan, Stillman, Althea A., Ghosh, Ananda K., Bilguvar, Kaya, O'Roak, Brian J., Mason, Christopher E., Abbott, Thomas, Gupta, Abha, King, Robert A., Pauls, David L., Tischfield, Jay A., Heiman, Gary A., Singer, Harvey S., Gilbert, Donald L., Hoekstra, Pieter J., Morgan, Thomas M., Loring, Erin, Yasuno, Katsuhito, Fernandez, Thomas, Sanders, Stephan, Louvi, Angeliki, Cho, Judy H., Mane, Shrikant, Colangelo, Christopher M., Biederer, Thomas, Lifton, Richard P., Gunel, Murat, and State, Matthew W.

Subjects
Decarboxylases -- Genetic aspects, Gene mutations -- Analysis, Histidine -- Research, Tourette's syndrome -- Genetic aspects, Tourette's syndrome -- Diagnosis, Tourette's syndrome -- Care and treatment
Abstract

An analysis of linkage in a two-generation pedigree leading to the identification of a rare functional mutation in the HDC gene encoding L-histidine decarboxylase and Tourette's syndrome, the rate-limiting enzyme in histamine biosynthesis is described. The study findings along with the published data from model system provide insight into the role for histaminergic neurotransmission in the mechanism and modulation of Tourette's syndrome and tics.

Published
2010

30. Molecular cytogenetic analysis and resequencing of contactin associated protein-like 2 in autism spectrum disorders

Author

Bakkaloglu, Betul, O'Roak, Brian J., Louvi, Angeliki, Gupta, Abha R., Abelson, Jesse F., Morgan, Thomas M., Chawarska, Katarzyna, Klin, Ami, Ercan-Sencicek, A. Gulhan, Stillman, Althea A., Tanriover, Gamze, Abrahams, Brett S., Duvall, Jackie A., Robbins, Elissa M., Geshwind, Daniel H., Biederer, Thomas, Gunel, Murat, Lifton, Richard P., and State, Matthew W.

Subjects
Human cytogenetics -- Research, Autistic children -- Genetic aspects, Autistic children -- Research, Amino acid sequence -- Research, Biological sciences
Abstract

A de novo chromosome 7q inversion disrupting Autism susceptibility candidate 2 (AUTS2) and Contactin Associated Protein-Like 2 (CNTNAP2) in a child with congitive and social delay is identified. It is suggested that rare variants contribute to the pathophysiology of autism spectrum disorders (ASD).

Published
2008

31. Synaptic and supra-synaptic organisation of the dopaminergic projection to the striatum

Author

Pfeffer, Marlene E., Pronot, Marie, Angelo, Maria-Florencia, Walle, Roman, Cordelières, Fabrice P., Levet, Florian, Claverol, Stéphane, Lacomme, Sabrina, Petrel, Melina, Martin, Christelle, Pitard, Vincent, Desmedt-Peyrusse, Véronique, Biederer, Thomas, Trifilieff, Pierre, Herzog, Etienne, Interdisciplinary Institute for Neuroscience (IINS), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract

SUMMARY Dopamine transmission is a monoaminergic system involved in reward processing and motor control. Volume transmission is thought to be the main mechanism by which monoamines modulate effector transmission though synaptic structures are scarcely described. Here, we applied a fluorescence activated synaptosome sorting workflow to dopaminergic projections to the striatum and explored cellular and molecular features of the dopaminergic synaptome. This demonstrated that dopaminergic varicosities adhere to post-synaptic membrane baring cognate receptors. We further identified a specific bond of varicosities to glutamatergic or GABAergic synapses in structures we named dopaminergic “hub synapses”. Finally, we showed that the synaptic adhesion protein SynCAM 2 is strongly expressed at dopaminergic hub synapses. Our data strongly suggest that neuromodulation frequently operates from hub-synapses on local receptors, presumably in conjunction with extra-synaptic volume transmission. We provide a new framework for the molecular exploration of dopaminergic synapses and more generally on discrete synapse populations ex-vivo. Highlights Fluorescence Activated Synaptosome Sorting allows for the establishment of a molecular synaptome of striatal dopaminergic projections. Dopaminergic varicosities adhere to receptor filled post-synaptic membranes. Dopaminergic projections build hub synapses with excitatory and inhibitory projections. SynCAM 2 is a strong candidate for the adhesion and differentiation of dopamine-effector hub synapses.

Published
2020

32. 3D Adaptive Optical Nanoscopy for Thick Specimen Imaging at sub-50 nm Resolution

Author

Hao, Xiang, primary, Allgeyer, Edward S., additional, Antonello, Jacopo, additional, Watters, Katherine, additional, Gerdes, Julianne A., additional, Schroeder, Lena K., additional, Bottanelli, Francesca, additional, Zhao, Jiaxi, additional, Kidd, Phylicia, additional, Lessard, Mark D., additional, Rothman, James E., additional, Cooley, Lynn, additional, Biederer, Thomas, additional, Booth, Martin J., additional, and Bewersdorf, Joerg, additional

Published
2020
Full Text
View/download PDF

34. SynCAM, a synaptic adhesion molecule that drives synapse assembly. (Research Articles)

Author

Biederer, Thomas, Sara, Yildirim, Mozhayeva, Marina, Atasoy, Deniz, Liu, Xinran, Kavalali, Ege T., and Sudhof, Thomas C.

Subjects
Synapses -- Composition -- Research, Neural transmission -- Research, Science and technology, Composition, Research
Abstract

Synapses, the junctions between nerve cells through which they communicate, are formed by the coordinated assembly and tight attachment of pre- and postsynaptic specializations. We now show that SynCAM is a brain-specific, immunoglobulin domain-containing protein that binds to intracellular PDZ-domain proteins and functions as a homophilic cell adhesion molecule at the synapse. Expression of the isolated cytoplasmic tail of SynCAM in neurons inhibited synapse assembly. Conversely, expression of full-length SynCAM in nonneuronal cells induced synapse formation by cocultured hippocampal neurons with normal release properties. Glutamatergic synaptic transmission was reconstituted in these nonneuronal cells by coexpressing glutamate receptors with SynCAM, which suggests that a single type of adhesion molecule and glutamate receptor are sufficient for a functional postsynaptic response., Synapses are specialized intercellular junctions that are assembled when an immature presynaptic terminal contacts a postsynaptic cell. At the site of contact, the presynaptic plasma membrane develops into an active [...]

Published
2002

38. FARP‐1 deletion is associated with lack of response to autism treatment by early start denver model in a multiplex family

Author

Cucinotta, Francesca, primary, Ricciardello, Arianna, additional, Turriziani, Laura, additional, Calabrese, Giorgia, additional, Briguglio, Marilena, additional, Boncoddo, Maria, additional, Bellomo, Fabiana, additional, Tomaiuolo, Pasquale, additional, Martines, Silvia, additional, Bruschetta, Marianna, additional, La Fauci Belponer, Francesca, additional, Di Bella, Tiziana, additional, Colombi, Costanza, additional, Baccarin, Marco, additional, Picinelli, Chiara, additional, Castronovo, Paola, additional, Lintas, Carla, additional, Sacco, Roberto, additional, Biederer, Thomas, additional, Kellam, Barbara, additional, Scherer, Stephen W., additional, and Persico, Antonio M., additional

Published
2020
Full Text
View/download PDF

40. Synaptomic analysis of dopaminergic inputs reveal hub synapses in the mouse striatum

Author

Paget-Blanc, Vincent, primary, Pfeffer, Marlene E., additional, Pronot, Marie, additional, Lapios, Paul, additional, Angelo, Maria-Florencia, additional, Walle, Roman, additional, Cordelières, Fabrice P., additional, Levet, Florian, additional, Claverol, Stéphane, additional, Lacomme, Sabrina, additional, Petrel, Melina, additional, Martin, Christelle, additional, Pitard, Vincent, additional, Desmedt-Peyrusse, Véronique, additional, Biederer, Thomas, additional, Perrais, David, additional, Trifilieff, Pierre, additional, and Herzog, Etienne, additional

Published
2020
Full Text
View/download PDF

42. Emerging Roles of Synapse Organizers in the Regulation of Critical Periods

Author

Ribic, Adema and Biederer, Thomas

Subjects
Article Subject
Abstract

Experience remodels cortical connectivity during developmental windows called critical periods. Experience-dependent regulation of synaptic strength during these periods establishes circuit functions that are stabilized as critical period plasticity wanes. These processes have been extensively studied in the developing visual cortex, where critical period opening and closure are orchestrated by the assembly, maturation, and strengthening of distinct synapse types. The synaptic specificity of these processes points towards the involvement of distinct molecular pathways. Attractive candidates are pre- and postsynaptic transmembrane proteins that form adhesive complexes across the synaptic cleft. These synapse-organizing proteins control synapse development and maintenance and modulate structural and functional properties of synapses. Recent evidence suggests that they have pivotal roles in the onset and closure of the critical period for vision. In this review, we describe roles of synapse-organizing adhesion molecules in the regulation of visual critical period plasticity and we discuss the potential they offer to restore circuit functions in amblyopia and other neurodevelopmental disorders.

Published
2019
Full Text
View/download PDF

43. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

Author

Sub Cell Biology, Celbiologie, Koopmans, Frank, van Nierop, Pim, Andres-Alonso, Maria, Byrnes, Andrea, Cijsouw, Tony, Coba, Marcelo P, Cornelisse, L Niels, Farrell, Ryan J, Goldschmidt, Hana L, Howrigan, Daniel P, Hussain, Natasha K, Imig, Cordelia, de Jong, Arthur P H, Jung, Hwajin, Kohansalnodehi, Mahdokht, Kramarz, Barbara, Lipstein, Noa, Lovering, Ruth C, MacGillavry, Harold, Mariano, Vittoria, Mi, Huaiyu, Ninov, Momchil, Osumi-Sutherland, David, Pielot, Rainer, Smalla, Karl-Heinz, Tang, Haiming, Tashman, Katherine, Toonen, Ruud F G, Verpelli, Chiara, Reig-Viader, Rita, Watanabe, Kyoko, van Weering, Jan, Achsel, Tilmann, Ashrafi, Ghazaleh, Asi, Nimra, Brown, Tyler C, De Camilli, Pietro, Feuermann, Marc, Foulger, Rebecca E, Gaudet, Pascale, Joglekar, Anoushka, Kanellopoulos, Alexandros, Malenka, Robert, Nicoll, Roger A, Pulido, Camila, de Juan-Sanz, Jaime, Sheng, Morgan, Südhof, Thomas C, Tilgner, Hagen U, Bagni, Claudia, Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Dieterich, Daniela C, Gundelfinger, Eckart D, Hoogenraad, Casper, Huganir, Richard L, Jahn, Reinhard, Kaeser, Pascal S, Kim, Eunjoon, Kreutz, Michael R, McPherson, Peter S, Neale, Ben M, O'Connor, Vincent, Posthuma, Danielle, Ryan, Timothy A, Sala, Carlo, Feng, Guoping, Hyman, Steven E, Thomas, Paul D, Smit, August B, Verhage, Matthijs, Sub Cell Biology, Celbiologie, Koopmans, Frank, van Nierop, Pim, Andres-Alonso, Maria, Byrnes, Andrea, Cijsouw, Tony, Coba, Marcelo P, Cornelisse, L Niels, Farrell, Ryan J, Goldschmidt, Hana L, Howrigan, Daniel P, Hussain, Natasha K, Imig, Cordelia, de Jong, Arthur P H, Jung, Hwajin, Kohansalnodehi, Mahdokht, Kramarz, Barbara, Lipstein, Noa, Lovering, Ruth C, MacGillavry, Harold, Mariano, Vittoria, Mi, Huaiyu, Ninov, Momchil, Osumi-Sutherland, David, Pielot, Rainer, Smalla, Karl-Heinz, Tang, Haiming, Tashman, Katherine, Toonen, Ruud F G, Verpelli, Chiara, Reig-Viader, Rita, Watanabe, Kyoko, van Weering, Jan, Achsel, Tilmann, Ashrafi, Ghazaleh, Asi, Nimra, Brown, Tyler C, De Camilli, Pietro, Feuermann, Marc, Foulger, Rebecca E, Gaudet, Pascale, Joglekar, Anoushka, Kanellopoulos, Alexandros, Malenka, Robert, Nicoll, Roger A, Pulido, Camila, de Juan-Sanz, Jaime, Sheng, Morgan, Südhof, Thomas C, Tilgner, Hagen U, Bagni, Claudia, Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Dieterich, Daniela C, Gundelfinger, Eckart D, Hoogenraad, Casper, Huganir, Richard L, Jahn, Reinhard, Kaeser, Pascal S, Kim, Eunjoon, Kreutz, Michael R, McPherson, Peter S, Neale, Ben M, O'Connor, Vincent, Posthuma, Danielle, Ryan, Timothy A, Sala, Carlo, Feng, Guoping, Hyman, Steven E, Thomas, Paul D, Smit, August B, and Verhage, Matthijs

Published
2019

44. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

Author

Koopmans, F., van Nierop, Pim, Andres-Alonso, M., Byrnes, Andrea, Cijsouw, Tony, Coba, Marcelo P., Cornelisse, L. Niels, Farrell, Ryan J., Goldschmidt, Hana L., Howrigan, Daniel P., Hussain, Natasha K., Imig, Cordelia, de Jong, Arthur P.H., Jung, Hwajin, Kohansalnodehi, Mahdokht, Kramarz, Barbara, Lipstein, Noa, Lovering, Ruth C., MacGillavry, Harold, Mariano, Vittoria, Mi, Huaiyu, Ninov, Momchil, Osumi-Sutherland, D., Pielot, Rainer, Smalla, Karl Heinz, Tang, Haiming, Tashman, Katherine, Toonen, Ruud F.G., Verpelli, Chiara, Reig-Viader, Rita, Watanabe, K., van Weering, Jan, Achsel, Tilmann, Ashrafi, Ghazaleh, Asi, N., Brown, Tyler C., De Camilli, Pietro, Feuermann, Marc, Foulger, Rebecca E., Gaudet, Pascale, Joglekar, Anoushka, Kanellopoulos, Alexandros, Malenka, Robert, Nicoll, Roger A., Pulido, Camila, de Juan-Sanz, J., Sheng, Morgan, Südhof, Thomas C., Tilgner, Hagen U., Bagni, Claudia, Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Dieterich, Daniela C., Gundelfinger, Eckart D., Hoogenraad, Casper, Huganir, Richard L., Jahn, Reinhard, Kaeser, Pascal S., Kim, Eunjoon, Kreutz, Michael R., McPherson, Peter S., Neale, B. M., O'Connor, Vincent, Posthuma, Danielle, Ryan, Timothy A., Sala, C., Feng, Guoping, Hyman, Steven E., Thomas, Paul D., Smit, August B., Verhage, Matthijs, Koopmans, F., van Nierop, Pim, Andres-Alonso, M., Byrnes, Andrea, Cijsouw, Tony, Coba, Marcelo P., Cornelisse, L. Niels, Farrell, Ryan J., Goldschmidt, Hana L., Howrigan, Daniel P., Hussain, Natasha K., Imig, Cordelia, de Jong, Arthur P.H., Jung, Hwajin, Kohansalnodehi, Mahdokht, Kramarz, Barbara, Lipstein, Noa, Lovering, Ruth C., MacGillavry, Harold, Mariano, Vittoria, Mi, Huaiyu, Ninov, Momchil, Osumi-Sutherland, D., Pielot, Rainer, Smalla, Karl Heinz, Tang, Haiming, Tashman, Katherine, Toonen, Ruud F.G., Verpelli, Chiara, Reig-Viader, Rita, Watanabe, K., van Weering, Jan, Achsel, Tilmann, Ashrafi, Ghazaleh, Asi, N., Brown, Tyler C., De Camilli, Pietro, Feuermann, Marc, Foulger, Rebecca E., Gaudet, Pascale, Joglekar, Anoushka, Kanellopoulos, Alexandros, Malenka, Robert, Nicoll, Roger A., Pulido, Camila, de Juan-Sanz, J., Sheng, Morgan, Südhof, Thomas C., Tilgner, Hagen U., Bagni, Claudia, Bayés, Àlex, Biederer, Thomas, Brose, Nils, Chua, John Jia En, Dieterich, Daniela C., Gundelfinger, Eckart D., Hoogenraad, Casper, Huganir, Richard L., Jahn, Reinhard, Kaeser, Pascal S., Kim, Eunjoon, Kreutz, Michael R., McPherson, Peter S., Neale, B. M., O'Connor, Vincent, Posthuma, Danielle, Ryan, Timothy A., Sala, C., Feng, Guoping, Hyman, Steven E., Thomas, Paul D., Smit, August B., and Verhage, Matthijs

Abstract

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders (“synaptopathies”). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org). The SynGO consortium presents a framework to annotate synaptic protein locations and functions and annotations for 1,112 synaptic genes based on published experimental evidence. SynGO reports exceptional features and disease associations for synaptic genes and provides an online data analysis platform.

Published
2019
Full Text
View/download PDF

45. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

Author

Koopmans, Frank, primary, van Nierop, Pim, additional, Andres-Alonso, Maria, additional, Byrnes, Andrea, additional, Cijsouw, Tony, additional, Coba, Marcelo P., additional, Cornelisse, L. Niels, additional, Farrell, Ryan J., additional, Goldschmidt, Hana L., additional, Howrigan, Daniel P., additional, Hussain, Natasha K., additional, Imig, Cordelia, additional, de Jong, Arthur P.H., additional, Jung, Hwajin, additional, Kohansalnodehi, Mahdokht, additional, Kramarz, Barbara, additional, Lipstein, Noa, additional, Lovering, Ruth C., additional, MacGillavry, Harold, additional, Mariano, Vittoria, additional, Mi, Huaiyu, additional, Ninov, Momchil, additional, Osumi-Sutherland, David, additional, Pielot, Rainer, additional, Smalla, Karl-Heinz, additional, Tang, Haiming, additional, Tashman, Katherine, additional, Toonen, Ruud F.G., additional, Verpelli, Chiara, additional, Reig-Viader, Rita, additional, Watanabe, Kyoko, additional, van Weering, Jan, additional, Achsel, Tilmann, additional, Ashrafi, Ghazaleh, additional, Asi, Nimra, additional, Brown, Tyler C., additional, De Camilli, Pietro, additional, Feuermann, Marc, additional, Foulger, Rebecca E., additional, Gaudet, Pascale, additional, Joglekar, Anoushka, additional, Kanellopoulos, Alexandros, additional, Malenka, Robert, additional, Nicoll, Roger A., additional, Pulido, Camila, additional, de Juan-Sanz, Jaime, additional, Sheng, Morgan, additional, Südhof, Thomas C., additional, Tilgner, Hagen U., additional, Bagni, Claudia, additional, Bayés, Àlex, additional, Biederer, Thomas, additional, Brose, Nils, additional, Chua, John Jia En, additional, Dieterich, Daniela C., additional, Gundelfinger, Eckart D., additional, Hoogenraad, Casper, additional, Huganir, Richard L., additional, Jahn, Reinhard, additional, Kaeser, Pascal S., additional, Kim, Eunjoon, additional, Kreutz, Michael R., additional, McPherson, Peter S., additional, Neale, Ben M., additional, O’Connor, Vincent, additional, Posthuma, Danielle, additional, Ryan, Timothy A., additional, Sala, Carlo, additional, Feng, Guoping, additional, Hyman, Steven E., additional, Thomas, Paul D., additional, Smit, August B., additional, and Verhage, Matthijs, additional

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results