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DC Field | Value | Language |
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dc.contributor.author | Rheenen, Wouter van | - |
dc.contributor.author | Spek, Rick A.A. van der | - |
dc.contributor.author | Bakker, Mark K. | - |
dc.contributor.author | Vugt, Joke J.F.A. van | - |
dc.contributor.author | Hop, Paul J. | - |
dc.contributor.author | Zwamborn, Ramona A. J. | - |
dc.contributor.author | Klein, Niek de | - |
dc.contributor.author | Westra, Harm-Jan | - |
dc.contributor.author | Bakker, Olivier B. | - |
dc.contributor.author | Deelen, Patrick | - |
dc.contributor.author | Shireby, Gemma | - |
dc.contributor.author | Hannon, Eilis | - |
dc.contributor.author | Moisse, Matthieu | - |
dc.contributor.author | Baird, Denis | - |
dc.contributor.author | Restuadi, Restuadi | - |
dc.contributor.author | Dolzhenko, Egor | - |
dc.contributor.author | Dekker, Annelot M. | - |
dc.contributor.author | Gawor, Klara | - |
dc.contributor.author | Westeneng, Henk-Jan | - |
dc.contributor.author | Tazelaar, Gijs H.P. | - |
dc.contributor.author | Eijk, Kristel R. van | - |
dc.contributor.author | Kooyman, Maarten | - |
dc.contributor.author | Byrne, Ross P. | - |
dc.contributor.author | Doherty, Mark | - |
dc.contributor.author | Heverin, Mark | - |
dc.contributor.author | Khleifat, Ahmad Al | - |
dc.contributor.author | Iacoangeli, Alfredo | - |
dc.contributor.author | Shatunov, Aleksey | - |
dc.contributor.author | Ticozzi, Nicola | - |
dc.contributor.author | Cooper-Knock, Johnathan | - |
dc.contributor.author | Smith, Bradley N. | - |
dc.contributor.author | Gromicho, Marta | - |
dc.contributor.author | Chandran, Siddharthan | - |
dc.contributor.author | Pal, Suvankar | - |
dc.contributor.author | Morrison, Karen E. | - |
dc.contributor.author | Shaw, Pamela J. | - |
dc.contributor.author | Hardy, John | - |
dc.contributor.author | Orrell, Richard W. | - |
dc.contributor.author | Sendtner, Michael | - |
dc.contributor.author | Meyer, Thomas | - |
dc.contributor.author | Başak, Nazli | - |
dc.contributor.author | Kooi, Anneke J. van der | - |
dc.contributor.author | Ratti, Antonia | - |
dc.contributor.author | Fogh, Isabella | - |
dc.contributor.author | Gellera, Cinzia | - |
dc.contributor.author | Lauria, Giuseppe | - |
dc.contributor.author | Corti, Stefania | - |
dc.contributor.author | Cereda, Cristina | - |
dc.contributor.author | Sproviero, Daisy | - |
dc.contributor.author | D’Alfonso, Sandra | - |
dc.contributor.author | Sorarù, Gianni | - |
dc.contributor.author | Siciliano, Gabriele | - |
dc.contributor.author | Filosto, Massimiliano | - |
dc.contributor.author | Padovani, Alessandro | - |
dc.contributor.author | Chiò, Adriano | - |
dc.contributor.author | Calvo, Andrea | - |
dc.contributor.author | Moglia, Cristina | - |
dc.contributor.author | Brunetti, Maura | - |
dc.contributor.author | Canosa, Antonio | - |
dc.contributor.author | Grassano, Maurizio | - |
dc.contributor.author | Beghi, Ettore | - |
dc.contributor.author | Pupillo, Elisabetta | - |
dc.contributor.author | Logroscino, Giancarlo | - |
dc.contributor.author | Nefussy, Beatrice | - |
dc.contributor.author | Osmanovic, Alma | - |
dc.contributor.author | Nordin, Angelica | - |
dc.contributor.author | Lerner, Yossef | - |
dc.contributor.author | Zabari, Michal | - |
dc.contributor.author | Gotkine, Marc | - |
dc.contributor.author | Baloh, Robert H. | - |
dc.contributor.author | Bell, Shaughn | - |
dc.contributor.author | Vourc’h, Patrick | - |
dc.contributor.author | Corcia, Philippe | - |
dc.contributor.author | Couratier, Philippe | - |
dc.contributor.author | Millecamps, Stéphanie | - |
dc.contributor.author | Meininger, Vincent | - |
dc.contributor.author | Salachas, François | - |
dc.contributor.author | Mora Pardina, Jesus S. | - |
dc.contributor.author | Assialioui, Abdelilah | - |
dc.contributor.author | Rojas-García, Ricardo | - |
dc.contributor.author | Dion, Patrick A. | - |
dc.contributor.author | Ross, Jay P. | - |
dc.contributor.author | Ludolph, Albert C. | - |
dc.contributor.author | Weishaupt, Jochen H. | - |
dc.contributor.author | Brenner, David | - |
dc.contributor.author | Freischmidt, Axel | - |
dc.contributor.author | Bensimon, Gilbert | - |
dc.contributor.author | Brice, Alexis | - |
dc.contributor.author | Durr, Alexandra | - |
dc.contributor.author | Payan, Christine A.M. | - |
dc.contributor.author | Saker-Delye, Safa | - |
dc.contributor.author | Wood, Nicholas W. | - |
dc.contributor.author | Topp, Simon | - |
dc.contributor.author | Rademakers, Rosa | - |
dc.contributor.author | Tittmann, Lukas | - |
dc.contributor.author | Lieb, Wolfgang | - |
dc.contributor.author | Franke, Andre | - |
dc.contributor.author | Ripke, Stephan | - |
dc.contributor.author | Braun, Alice | - |
dc.contributor.author | Kraft, Julia | - |
dc.contributor.author | Whiteman, David C. | - |
dc.contributor.author | Olsen, Catherine M. | - |
dc.contributor.author | Uitterlinden, Andre G. | - |
dc.contributor.author | Hofman, Albert | - |
dc.contributor.author | Rietschel, Marcella | - |
dc.contributor.author | Cichon, Sven | - |
dc.contributor.author | Nöthen, Markus M. | - |
dc.contributor.author | Amouyel, Philippe | - |
dc.contributor.author | Traynor, Bryan J. | - |
dc.contributor.author | Singleton, Andrew B. | - |
dc.contributor.author | Mitne Neto, Miguel | - |
dc.contributor.author | Cauchi, Ruben J. | - |
dc.contributor.author | Ophoff, Roel A. | - |
dc.contributor.author | Wiedau-Pazos, Martina | - |
dc.contributor.author | Lomen-Hoerth, Catherine | - |
dc.contributor.author | Deerlin, Vivianna M. van | - |
dc.contributor.author | Grosskreutz, Julian | - |
dc.contributor.author | Roediger, Annekathrin | - |
dc.contributor.author | Gaur, Nayana | - |
dc.contributor.author | Jörk, Alexander | - |
dc.contributor.author | Barthel, Tabea | - |
dc.contributor.author | Theele, Erik | - |
dc.contributor.author | Ilse, Benjamin | - |
dc.contributor.author | Stubendorff, Beatrice | - |
dc.contributor.author | Witte, Otto W. | - |
dc.contributor.author | Steinbach, Robert | - |
dc.contributor.author | Hübner, Christian A. | - |
dc.contributor.author | Graff, Caroline | - |
dc.contributor.author | Brylev, Lev | - |
dc.contributor.author | Fominykh, Vera | - |
dc.contributor.author | Demeshonok, Vera | - |
dc.contributor.author | Ataulina, Anastasia | - |
dc.contributor.author | Rogelj, Boris | - |
dc.contributor.author | Koritnik, Blaž | - |
dc.contributor.author | Zidar, Janez | - |
dc.contributor.author | Ravnik-Glavač, Metka | - |
dc.contributor.author | Glavač, Damjan | - |
dc.contributor.author | Stević, Zorica | - |
dc.contributor.author | Drory, Vivian | - |
dc.contributor.author | Povedano, Monica | - |
dc.contributor.author | Blair, Ian P. | - |
dc.contributor.author | Kiernan, Matthew C. | - |
dc.contributor.author | Benyamin, Beben | - |
dc.contributor.author | Henderson, Robert D. | - |
dc.contributor.author | Furlong, Sarah | - |
dc.contributor.author | Mathers, Susan | - |
dc.contributor.author | McCombe, Pamela A. | - |
dc.contributor.author | Needham, Merrilee | - |
dc.contributor.author | Ngo, Shyuan T. | - |
dc.contributor.author | Nicholson, Garth A. | - |
dc.contributor.author | Pamphlett, Roger | - |
dc.contributor.author | Rowe, Dominic B. | - |
dc.contributor.author | Steyn, Frederik J. | - |
dc.contributor.author | Williams, Kelly L. | - |
dc.contributor.author | Mather, Karen A. | - |
dc.contributor.author | Sachdev, Perminder S. | - |
dc.contributor.author | Henders, Anjali K. | - |
dc.contributor.author | Wallace, Leanne | - |
dc.contributor.author | Carvalho, Mamede de | - |
dc.contributor.author | Pinto, Susana | - |
dc.contributor.author | Petri, Susanne | - |
dc.contributor.author | Weber, Markus | - |
dc.contributor.author | Rouleau, Guy A. | - |
dc.contributor.author | Silani, Vincenzo | - |
dc.contributor.author | Curtis, Charles J. | - |
dc.contributor.author | Breen, Gerome | - |
dc.contributor.author | Glass, Jonathan D. | - |
dc.contributor.author | Brown Jr., Robert H. | - |
dc.contributor.author | Landers, John E. | - |
dc.contributor.author | Shaw, Christopher E. | - |
dc.contributor.author | Andersen, Peter M. | - |
dc.contributor.author | Groen, Ewout J.N. | - |
dc.contributor.author | Es, Michael A. van | - |
dc.contributor.author | Jeroen Pasterkamp, R. | - |
dc.contributor.author | Fan, Dongsheng | - |
dc.contributor.author | Garton, Fleur C. | - |
dc.contributor.author | McRae, Allan F. | - |
dc.contributor.author | Davey Smith, George | - |
dc.contributor.author | Gaunt, Tom R. | - |
dc.contributor.author | Eberle, Michael A. | - |
dc.contributor.author | Mill, Jonathan | - |
dc.contributor.author | McLaughlin, Russell L. | - |
dc.contributor.author | Hardiman, Orla | - |
dc.contributor.author | Kenna, Kevin P. | - |
dc.contributor.author | Wray, Naomi R. | - |
dc.contributor.author | Tsai, Ellen | - |
dc.contributor.author | Runz, Heiko | - |
dc.contributor.author | Franke, Lude | - |
dc.contributor.author | Al-Chalabi, Ammar | - |
dc.contributor.author | Damme, Philip Van | - |
dc.contributor.author | Berg, Leonard H. van den | - |
dc.contributor.author | Veldink, Jan H. | - |
dc.date.accessioned | 2022-11-09T06:16:43Z | - |
dc.date.available | 2022-11-09T06:16:43Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Van Rheenen, W., Van Der Spek, R. A., Bakker, M. K., Van Vugt, J. J., Hop, P. J., Zwamborn, R. A., ... & Nicholson, G. A. (2021). Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nature genetics, 53(12), 1636-1648. | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar/handle/123456789/103513 | - |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. | en_GB |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.rights | info:eu-repo/semantics/openAccess | en_GB |
dc.subject | Genomes | en_GB |
dc.subject | Amyotrophic lateral sclerosis -- Diagnosis | en_GB |
dc.subject | Nervous system -- Degeneration | en_GB |
dc.title | Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology | en_GB |
dc.type | article | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.contributor.corpauthor | SLALOM Consortium | en_GB |
dc.contributor.corpauthor | PARALS Consortium | en_GB |
dc.contributor.corpauthor | SLAGEN Consortium | en_GB |
dc.contributor.corpauthor | SLAP Consortium | en_GB |
dc.description.reviewed | peer-reviewed | en_GB |
dc.identifier.doi | 10.1038/s41588-021-00973-1 | - |
dc.publication.title | Nature genetics | en_GB |
Appears in Collections: | Scholarly Works - FacM&SPB |
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Common and_rare_variant_association_analyses_in_amyotrophic_lateral_sclerosis_identify_15_risk_loci_with_distinct_genetic_architectures_and_neuron_specific_biology.pdf | 9.35 MB | Adobe PDF | View/Open |
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