Authors
Wouter Van Rheenen, Rick AA Van Der Spek, Mark K Bakker, Joke JFA Van Vugt, Paul J Hop, Ramona AJ Zwamborn, Niek De Klein, Harm-Jan Westra, Olivier B Bakker, Patrick Deelen, Gemma Shireby, Eilis Hannon, Matthieu Moisse, Denis Baird, Restuadi Restuadi, Egor Dolzhenko, Annelot M Dekker, Klara Gawor, Henk-Jan Westeneng, Gijs HP Tazelaar, Kristel R van Eijk, Maarten Kooyman, Ross P Byrne, Mark Doherty, Mark Heverin, Ahmad Al Khleifat, Alfredo Iacoangeli, Aleksey Shatunov, Nicola Ticozzi, Johnathan Cooper-Knock, Bradley N Smith, Marta Gromicho, Siddharthan Chandran, Suvankar Pal, Karen E Morrison, Pamela J Shaw, John Hardy, Richard W Orrell, Michael Sendtner, Thomas Meyer, Nazli Başak, Anneke J van der Kooi, Antonia Ratti, Isabella Fogh, Cinzia Gellera, Giuseppe Lauria, Stefania Corti, Cristina Cereda, Daisy Sproviero, Sandra D’Alfonso, Gianni Sorarù, Gabriele Siciliano, Massimiliano Filosto, Alessandro Padovani, Adriano Chiò, Andrea Calvo, Cristina Moglia, Maura Brunetti, Antonio Canosa, Maurizio Grassano, Ettore Beghi, Elisabetta Pupillo, Giancarlo Logroscino, Beatrice Nefussy, Alma Osmanovic, Angelica Nordin, Yossef Lerner, Michal Zabari, Marc Gotkine, Robert H Baloh, Shaughn Bell, Patrick Vourc’h, Philippe Corcia, Philippe Couratier, Stéphanie Millecamps, Vincent Meininger, François Salachas, Jesus S Mora Pardina, Abdelilah Assialioui, Ricardo Rojas-García, Patrick A Dion, Jay P Ross, Albert C Ludolph, Jochen H Weishaupt, David Brenner, Axel Freischmidt, Gilbert Bensimon, Alexis Brice, Alexandra Durr, Christine AM Payan, Safa Saker-Delye, Nicholas W Wood, Simon Topp, Rosa Rademakers, Lukas Tittmann, Wolfgang Lieb, Andre Franke, Stephan Ripke, Alice Braun, Julia Kraft, David C Whiteman, Catherine M Olsen, Andre G Uitterlinden, Albert Hofman, Marcella Rietschel, Sven Cichon, Markus M Nöthen, Philippe Amouyel, Bryan J Traynor, Andrew B Singleton, Miguel Mitne Neto, Ruben J Cauchi, Roel A Ophoff, Martina Wiedau-Pazos, Catherine Lomen-Hoerth, Vivianna M van Deerlin, Julian Grosskreutz, Annekathrin Roediger, Nayana Gaur, Alexander Jörk, Tabea Barthel, Erik Theele, Benjamin Ilse, Beatrice Stubendorff, Otto W Witte, Robert Steinbach, Christian A Hübner, Caroline Graff, Lev Brylev, Vera Fominykh, Vera Demeshonok, Anastasia Ataulina, Boris Rogelj, Blaž Koritnik, Janez Zidar, Metka Ravnik-Glavač, Damjan Glavač, Zorica Stević, Vivian Drory, Monica Povedano, Ian P Blair, Matthew C Kiernan, Beben Benyamin, Robert D Henderson, Sarah Furlong, Susan Mathers
Publication date
2021/12
Journal
Nature genetics
Volume
53
Issue
12
Pages
1636-1648
Publisher
Nature Publishing Group US
Description
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 …
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Scholar articles
W Van Rheenen, RAA Van Der Spek, MK Bakker… - Nature genetics, 2021