ITEM METADATA RECORD
Title: Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
Authors: van Rheenen, Wouter ×
Shatunov, Aleksey
Dekker, Annelot M
McLaughlin, Russell L
Diekstra, Frank P
Pulit, Sara L
van der Spek, Rick A A
Võsa, Urmo
de Jong, Simone
Robinson, Matthew R
Yang, Jian
Fogh, Isabella
van Doormaal, Perry Tc
Tazelaar, Gijs H P
Koppers, Max
Blokhuis, Anna M
Sproviero, William
Jones, Ashley R
Kenna, Kevin P
van Eijk, Kristel R
Harschnitz, Oliver
Schellevis, Raymond D
Brands, William J
Medic, Jelena
Menelaou, Androniki
Vajda, Alice
Ticozzi, Nicola
Lin, Kuang
Rogelj, Boris
Vrabec, Katarina
Ravnik-Glavač, Metka
Koritnik, Blaž
Zidar, Janez
Leonardis, Lea
Grošelj, Leja Dolenc
Millecamps, Stéphanie
Salachas, François
Meininger, Vincent
de Carvalho, Mamede
Pinto, Susana
Mora, Jesus S
Rojas-García, Ricardo
Polak, Meraida
Chandran, Siddharthan
Colville, Shuna
Swingler, Robert
Morrison, Karen E
Shaw, Pamela J
Hardy, John
Orrell, Richard W
Pittman, Alan
Sidle, Katie
Fratta, Pietro
Malaspina, Andrea
Topp, Simon
Petri, Susanne
Abdulla, Susanne
Drepper, Carsten
Sendtner, Michael
Meyer, Thomas
Ophoff, Roel A
Staats, Kim A
Wiedau-Pazos, Martina
Lomen-Hoerth, Catherine
Van Deerlin, Vivianna M
Trojanowski, John Q
Elman, Lauren
McCluskey, Leo
Basak, A Nazli
Tunca, Ceren
Hamzeiy, Hamid
Parman, Yesim
Meitinger, Thomas
Lichtner, Peter
Radivojkov-Blagojevic, Milena
Andres, Christian R
Maurel, Cindy
Bensimon, Gilbert
Landwehrmeyer, Bernhard
Brice, Alexis
Payan, Christine A M
Saker-Delye, Safaa
Dürr, Alexandra
Wood, Nicholas W
Tittmann, Lukas
Lieb, Wolfgang
Franke, Andre
Rietschel, Marcella
Cichon, Sven
Nöthen, Markus M
Amouyel, Philippe
Tzourio, Christophe
Dartigues, Jean-François
Uitterlinden, Andre G
Rivadeneira, Fernando
Estrada, Karol
Hofman, Albert
Curtis, Charles
Blauw, Hylke M
van der Kooi, Anneke J
de Visser, Marianne
Goris, An
Weber, Markus
Shaw, Christopher E
Smith, Bradley N
Pansarasa, Orietta
Cereda, Cristina
Del Bo, Roberto
Comi, Giacomo P
D'Alfonso, Sandra
Bertolin, Cinzia
Sorarù, Gianni
Mazzini, Letizia
Pensato, Viviana
Gellera, Cinzia
Tiloca, Cinzia
Ratti, Antonia
Calvo, Andrea
Moglia, Cristina
Brunetti, Maura
Arcuti, Simona
Capozzo, Rosa
Zecca, Chiara
Lunetta, Christian
Penco, Silvana
Riva, Nilo
Padovani, Alessandro
Filosto, Massimiliano
Muller, Bernard
Stuit, Robbert Jan
Blair, Ian
Zhang, Katharine
McCann, Emily P
Fifita, Jennifer A
Nicholson, Garth A
Rowe, Dominic B
Pamphlett, Roger
Kiernan, Matthew C
Grosskreutz, Julian
Witte, Otto W
Ringer, Thomas
Prell, Tino
Stubendorff, Beatrice
Kurth, Ingo
Hübner, Christian A
Leigh, P Nigel
Casale, Federico
Chio, Adriano
Beghi, Ettore
Pupillo, Elisabetta
Tortelli, Rosanna
Logroscino, Giancarlo
Powell, John
Ludolph, Albert C
Weishaupt, Jochen H
Robberecht, Wim
Van Damme, Philip
Franke, Lude
Pers, Tune H
Brown, Robert H
Glass, Jonathan D
Landers, John E
Hardiman, Orla
Andersen, Peter M
Corcia, Philippe
Vourc'h, Patrick
Silani, Vincenzo
Wray, Naomi R
Visscher, Peter M
de Bakker, Paul I W
van Es, Michael A
Pasterkamp, R Jeroen
Lewis, Cathryn M
Breen, Gerome
Al-Chalabi, Ammar
van den Berg, Leonard H
Veldink, Jan H #
Issue Date: Sep-2016
Publisher: Nature Publishing Group
Series Title: Nature Genetics vol:48 issue:9
Article number: 10.1038/ng.3622
Abstract: To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
URI: 
ISSN: 1061-4036
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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