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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
Neuron, Volume 97, No. 6, Year 2018
Notification
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Description
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Using a large-scale genome-wide association study and exome sequencing, we identified KIF5A as a novel gene associated with ALS. Our data broaden the phenotype resulting from mutations in KIF5A and highlight the importance of cytoskeletal defects in the pathogenesis of ALS. © 2018 Elsevier Inc.
Authors & Co-Authors
Nicolas, Aude
United States, Bethesda
National Institutes of Health Nih
Ticozzi, Nicola
Italy, Milan
Irccs Istituto Auxologico Italiano
Italy, Milan
Università Degli Studi Di Milano
Faghri, Faraz
United States, Bethesda
National Institutes of Health Nih
United States, Urbana
University of Illinois Urbana-champaign
Nalls, Mike A.
United States, Bethesda
National Institutes of Health Nih
United States, Glen Echo
Data Tecnica International
van Rheenen, Wouter
Netherlands, Utrecht
University Medical Center Utrecht
Abramzon, Yevgeniya A.
United States, Bethesda
National Institutes of Health Nih
United Kingdom, London
University College London
Eicher, John D.
United States, Rahway
Merck & Co., Inc.
Logroscino, Giancarlo C.
Unknown Affiliation
Mandich, Paola
Unknown Affiliation
Conforti, Francesca Luisa
Italy, Rome
Consiglio Nazionale Delle Ricerche
Penco, Silvana
Unknown Affiliation
Carrera, Paola
Unknown Affiliation
Ferrarese, Carlo
Unknown Affiliation
Tedeschi, Gioacchino M.
Unknown Affiliation
Sabatelli, Mario
Italy, Rome
Università Cattolica Del Sacro Cuore, Campus Di Roma
Zollino, Marcella
Unknown Affiliation
Luigetti, Marco
Unknown Affiliation
Restagno, Gabriella
Unknown Affiliation
Messina, Sonia
Italy, Messina
Università Degli Studi Di Messina
D’Alfonso, Sandra
Italy, Vercelli
Università Degli Studi Del Piemonte Orientale Amedeo Avogadro
Ferrucci, Luigi G.
United States, Bethesda
National Institutes of Health Nih
Harms, Matthew B.
United States, New York
Columbia University
Goldstein, David B.
United States, New York
Columbia University
Miller, Timothy M.
United States, St. Louis
Washington University School of Medicine in St. Louis
Chandran, Siddharthan
Unknown Affiliation
Pal, Suvankar
Unknown Affiliation
Moreno, Cristiane Araújo Martins
United States, New York
Columbia University
Allen, Andrew S.
Unknown Affiliation
Boone, Braden E.
Unknown Affiliation
Brown, Robert H.
United States, Worcester
University of Massachusetts Chan Medical School
Chesi, Alessandra
Unknown Affiliation
Chung, Wendy Kay
Unknown Affiliation
Cirulli, Elizabeth Trilby
Unknown Affiliation
Cooper, Gregory M.
Unknown Affiliation
Day-Williams, Aaron Garth
Unknown Affiliation
Dion, Patrick A.
Unknown Affiliation
Glass, Jonathan D.
United States, Atlanta
Emory University School of Medicine
Jones, Angela L.
Unknown Affiliation
Levy, Shawn E.
Unknown Affiliation
Maniatis, Tom
Unknown Affiliation
McKenna-Yasek, Diane M.
United States, Worcester
University of Massachusetts Chan Medical School
Petrovski, Slavé D.Sign©
Unknown Affiliation
Rouleau, Guy Armand
Canada, Montreal
Université Mcgill
Sapp, Peter C.
United States, Worcester
University of Massachusetts Chan Medical School
Waite, Lindsay L.
Unknown Affiliation
Broach, James R.
United States, Hershey
Penn State College of Medicine
van Deerlin, Vivianna M.D.
United States, Philadelphia
University of Pennsylvania
Baas, Frank F.
Netherlands, Leiden
Universiteit Leiden
Zaitlen, Noah A.
Unknown Affiliation
Cox, Gregory A.
Unknown Affiliation
Finkbeiner, Steven M.
United States, San Francisco
Gladstone Institute of Neurological Disease
United States, San Francisco
University of California, San Francisco
Dardiotis, Efthymios
Unknown Affiliation
Nath, Avindra
Unknown Affiliation
Musunuri, Rajeeva Lochan
United States, New York
New York Genome Center
Evani, Uday Shankar
United States, New York
New York Genome Center
Abhyankar, Avinash
United States, New York
New York Genome Center
Zody, Michael C.
United States, New York
New York Genome Center
van Eyk, Jennifer E.
United States, Los Angeles
Cedars-sinai Medical Center
Kolb, Stephen James
United States, Columbus
The Ohio State University Wexner Medical Center
Benatar, Michael G.
United States, Coral Gables
University of Miami
Wu, Gang
United States, Memphis
St. Jude Children's Research Hospital
Rampersaud, Evadnie
United States, Memphis
St. Jude Children's Research Hospital
Wuu, Joanne
United States, Coral Gables
University of Miami
Rademakers, Rosa V.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Züchner, Stephan L.
Unknown Affiliation
Schüle, Rebecca
Unknown Affiliation
McCauley, Jacob L.
Unknown Affiliation
Cooley, Anne
Unknown Affiliation
Barohn, Richard J.
Unknown Affiliation
Jackson, Carlayne E.
Unknown Affiliation
Heckmann, Jeannine M.
Unknown Affiliation
Walk, David
Unknown Affiliation
Maiser, Samuel J.
Unknown Affiliation
Ratti, Antonia
Italy, Milan
Irccs Istituto Auxologico Italiano
Italy, Milan
Università Degli Studi Di Milano
Taroni, Franco
Italy, Milan
Foundation Irccs Neurological Institute C. Besta
Lauria Pinter, Giuseppe
Italy, Milan
Università Degli Studi Di Milano
Comi, Giacomo Pietro
Italy, Bologna
Ospedale Maggiore
Sorarù, Gianni
Italy, Padua
Università Degli Studi Di Padova
Cereda, Cristina
Italy, Pavia
Irccs Fondazione Mondino
de Marchi, Fabiola D.
Unknown Affiliation
Siciliano, Gabriele
Unknown Affiliation
Peverelli, Silvia
Unknown Affiliation
Castellotti, B.
Unknown Affiliation
Camu, William
France, Montpellier
Hopital Gui de Chauliac
Lumbroso, Serge
France, Montpellier
Institut Des Neurosciences de Montpellier
France, Nimes
Centre Hospitalier Universitaire de Nîmes
Corcia, Philippe
France, Tours
Hopital Bretonneau
Lagrange, Emmeline
Unknown Affiliation
Clavelou, Pierre
Unknown Affiliation
Couratier, Philippe P.
Unknown Affiliation
Vourc'H, Patrick
Unknown Affiliation
Le-Masson, Gwendal
Unknown Affiliation
Hardy, John A.
United Kingdom, London
University College London
Singleton, Andrew B.
United States, Bethesda
National Institutes of Health Nih
Johnson, Janel O.
United States, Bethesda
National Institutes of Health Nih
Arepalli, Sampath K.
United States, Bethesda
National Institutes of Health Nih
Polak, Meraida A.
United States, Atlanta
Emory University School of Medicine
Al-Sarraj, Safa Taha
United Kingdom, London
King's College London
King, Andrew P.
United Kingdom, London
King's College London
Hernandez, Dena G.
United States, Bethesda
National Institutes of Health Nih
Ding, Jinhui
United States, Bethesda
National Institutes of Health Nih
Gibbs, J. Raphael
United States, Bethesda
National Institutes of Health Nih
Scholz, Sonja W.
United States, Bethesda
National Institutes of Health Nih
United States, Baltimore
Johns Hopkins University
R. Broach, James Harold
United States, Urbana
University of Illinois Urbana-champaign
Landi, Francesco L.
Italy, Rome
Università Cattolica Del Sacro Cuore, Campus Di Roma
Kirby, Janine
United Kingdom, Sheffield
The University of Sheffield
Gerhard, Glenn S.
United States, Hershey
Penn State College of Medicine
Troncoso, Juan Carlos
United States, Baltimore
Johns Hopkins School of Medicine
Le Ber, Isabelle
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Strom, Tim Matthias
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Meitinger, Thomas A.
Germany, Munich
Technische Universität München
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Munich Cluster for Systems Neurology Synergy
van Eijk, Kristel R.
Netherlands, Utrecht
University Medical Center Utrecht
De Carvalho, Mamede Alves
Portugal, Lisbon
Universidade de Lisboa
Portugal, Lisbon
Santa Maria Hospital, Lisbon
Moisse, Matthieu
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
McLaughlin, Russell Lewis
Ireland, Dublin
Trinity College Dublin
Van Blitterswijk, Marka M.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Morrison, Karen E.
United Kingdom, Southampton
University of Southampton
Basak, Nazli Nazli
Turkey, Bebek
Boğaziçi Üniversitesi
Drory, Vivian E.
Israel, Tel Aviv-yafo
Tel Aviv Sourasky Medical Center
Shaw, Pamela J.
United Kingdom, Sheffield
The University of Sheffield
Turner, Martin R.
United Kingdom, Oxford
University of Oxford
Talbot, Kevin
United Kingdom, Oxford
University of Oxford
Hardiman, Orla M.
Ireland, Dublin
Trinity College Dublin
Fifita, Jennifer A.
Australia, Sydney
Macquarie University
Nicholson, Garth A.
Australia, Sydney
Macquarie University
Australia, Sydney
Concord Repatriation General Hospital
Cooper-Knock, Johnathan
United Kingdom, Sheffield
The University of Sheffield
Dekker, Annelot M.
Unknown Affiliation
Landers, John E.
United States, Worcester
University of Massachusetts Chan Medical School
Newhouse, Stephen J.
Unknown Affiliation
Pinto, Susana
Unknown Affiliation
Pulit, Sara L.
Unknown Affiliation
Robberecht, Wim
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Leuven
Ku Leuven– University Hospital Leuven
Shaw, Christopher E.
Unknown Affiliation
van Damme, Philip
Belgium, Leuven
Ku Leuven
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Belgium, Leuven
Ku Leuven– University Hospital Leuven
van den Berg, Leonard H.
Netherlands, Utrecht
University Medical Center Utrecht
Veldink, Jan Herman
Netherlands, Utrecht
University Medical Center Utrecht
Zatz, Mayana
Unknown Affiliation
Bauer, Denis C.
Unknown Affiliation
Twine, Natalie A.
Unknown Affiliation
Rogaeva, Ekaterina A.
Canada, Toronto
University of Toronto
Brice, Alexis
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Ludolph, Albert Christian
Germany, Ulm
Universität Ulm
Weishaupt, Jochen Hans
Germany, Ulm
Universität Ulm
Traynor, B. J.
United States, Bethesda
National Institutes of Health Nih
United States, Baltimore
Johns Hopkins University
Statistics
Citations: 398
Authors: 143
Affiliations: 110
Identifiers
Doi:
10.1016/j.neuron.2018.02.027
ISSN:
08966273
Research Areas
Genetics And Genomics