Evidence map›Paper›PMID 29566793›Full record

ArticleNeuron2018

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.

Aude Nicolas, Kevin P Kenna, Alan E Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A Dominov, Brendan J Kenna, Mike A Nalls, Pamela Keagle and 203 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01459302 (Family Studies in Neuromuscular Disorders), which is not on this map. Cited by 436 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
436citing papers in PubMed, 5 pooled it
52.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01459302 withdrawnnot on this map

Family Studies in Neuromuscular Disorders

TypeobservationalSponsorUniversity of Massachusetts, WorcesterRan2009 to 2024Enrolled0ConditionsAmyotrophic Lateral Sclerosis, Frontotemporal Dementia, PLS, Motor Neuron Disease
3 · Its place in the literature

Who cites it

436 citing papers in PubMed, 5 syntheses or guidelines pooled it, 709 citations in OpenAlex.

  1. A systematic review and functionalFrontiers in neuroscience · 2025
    Pooled it
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  6. Article
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  10. Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
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  12. Review
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  20. TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026
    Review

376 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

213 authors at 20 institutions in 17 countries.

Aude NicolasNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Kevin P KennaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Alan E RentonNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Nicola TicozziDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center - Università degli Studi di Milano, Milan 20122, Italy.
Faraz FaghriMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Ruth ChiaNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Janice A DominovDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Brendan J KennaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Mike A NallsMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Data Tecnica International, Glen Echo, MD, USA.
Pamela KeagleDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Alberto M RiveraNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Wouter van RheenenDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Natalie A MurphyNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Joke J F A van VugtDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Joshua T GeigerNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Rick A Van der SpekDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Hannah A PlinerNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
ShankaracharyaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Bradley N SmithMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Giuseppe MarangiNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Institute of Genomic Medicine, Catholic University, Roma, Italy.
Simon D ToppMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Yevgeniya AbramzonNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Sobell Department of Motor Neuroscience and Movement Disorders, University College London, Institute of Neurology, London, UK.
Athina Soragia GkaziMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
John D EicherGenetics and Pharmacogenomics, MRL, Merck & Co., Inc., Boston, MA 02115, USA.
Aoife KennaDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
ITALSGEN Consortium
Gabriele MoraALS Center, Salvatore Maugeri Foundation, IRCCS, Mistretta, Messina, Italy.
Andrea Calvo"Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy.
Letizia Mazzini"Maggiore della Carità" University Hospital, Novara, Italy.
Nilo RivaDepartment of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Jessica MandrioliDepartment of Neuroscience, St. Agostino Estense Hospital, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
Claudia CaponnettoDepartment of Neurosciences, Ophthalmology, Genetics, Rehabilitation, Maternal and Child Health, Ospedale Policlinico San Martino, Genoa, Italy.
Stefania BattistiniDepartment of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Paolo VolantiALS Center, Salvatore Maugeri Foundation, IRCCS, Mistretta, Messina, Italy.
Vincenzo La BellaALS Clinical Research Center, University of Palermo, Palermo, Italy.
Francesca L ConfortiInstitute of Neurological Sciences, National Research Council, Mangone, Cosenza, Italy.
Giuseppe BorgheroDepartment of Neurology, Azienda Universitario Ospedaliera di Cagliari and University of Cagliari, Cagliari, Italy.
Sonia MessinaDepartment of Clinical and Experimental Medicine, University of Messina and Nemo Sud Clinical Center for Neuromuscular Diseases, Aurora Foundation, Messina, Italy.
Isabella L SimoneDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
Francesca TrojsiDepartment of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.
Fabrizio Salvi"Il Bene" Center for Immunological and Rare Neurological Diseases at Bellaria Hospital, IRCCS, Istituto delle Scienze Neurologiche, Bologna, Italy.
Francesco O LogulloNeurological Clinic, Marche Polytechnic University, Ancona, Italy.
Sandra D'AlfonsoDepartment of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Lucia CorradoDepartment of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Margherita CapassoDepartment of Neurology, University of Chieti, Chieti, Italy.
Luigi FerrucciLongitudinal Studies Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Genomic Translation for ALS Care (GTAC) Consortium
Cristiane de Araujo Martins MorenoDepartment of Neurology, Columbia University, New York, NY 10032, USA.
Sitharthan KamalakaranInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
David B GoldsteinInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
ALS Sequencing Consortium
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Tim HarrisBioverativ, 225 2nd Avenue, Waltham, MA 02145, USA.
Richard M MyersHudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
NYGC ALS Consortium
Hemali PhatnaniCenter for Genomics of Neurodegenerative Diseases (CGND), New York Genome Center, New York, NY, USA.
Rajeeva Lochan MusunuriComputational Biology, New York Genome Center, New York, NY, USA.
Uday Shankar EvaniComputational Biology, New York Genome Center, New York, NY, USA.
Avinash AbhyankarComputational Biology, New York Genome Center, New York, NY, USA.
Michael C ZodyComputational Biology, New York Genome Center, New York, NY, USA.
Answer ALS Foundation
Julia KayeGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Steven FinkbeinerGladstone Institute of Neurological Disease, San Francisco, CA, USA; Departments of Neurology and Physiology, University of California San Francisco, San Francisco, CA, USA.
Stacia K WymanGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Alex LeNailDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Leandro LimaGladstone Institute of Neurological Disease, San Francisco, CA, USA.
Ernest FraenkelDepartment of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
Clive N SvendsenBoard of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Leslie M ThompsonDepartment of Neurobiology and Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Department of Psychiatry and Human Behavior, Institute of Memory Impairment and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Jennifer E Van EykThe Heart Institute and Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
James D BerryHarvard Medical School, Department of Neurology, Massachusetts General Hospital (MGH), Boston, MA, USA; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA.
Timothy M MillerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Stephen J KolbDepartment of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Merit CudkowiczHarvard Medical School, Department of Neurology, Massachusetts General Hospital (MGH), Boston, MA, USA; Neurological Clinical Research Institute (NCRI), Massachusetts General Hospital, Boston, MA, USA.
Emily BaxiDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium
Michael BenatarDepartment of Neurology, University of Miami, Miami, FL 33136, USA.
J Paul TaylorHoward Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Evadnie RampersaudDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Gang WuDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Joanne WuuDepartment of Neurology, University of Miami, Miami, FL 33136, USA.
SLAGEN Consortium
Giuseppe Lauria3rd Neurology Unit, Motor Neuron Diseases Center, Fondazione IRCCS Istituto Neurologico "Carlo Besta," and Department of Biomedical and Clinical Sciences "Luigi Sacco," University of Milan, Milan, Italy.
Federico VerdeDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Isabella FoghDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Cinzia TilocaDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Giacomo P ComiNeurology Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Gianni SorarùDepartment of Neurosciences, University of Padova, Padova, Italy.
Cristina CeredaGenomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy.
French ALS Consortium
Philippe CorciaALS Center, CHU Bretonneau, Tours University, Tours, France.
Hannu LaaksovirtaDepartment of Neurology, Helsinki University Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki FIN-02900, Finland.
Liisa MyllykangasDepartment of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Lilja JanssonDepartment of Neurology, Helsinki University Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki FIN-02900, Finland.
Miko ValoriDepartment of Neurology, Helsinki University Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki FIN-02900, Finland.
John EalingGreater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK.
Hisham HamdallaGreater Manchester Neurosciences Centre, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK.
Sara RollinsonFaculty of Human and Medical Sciences, University of Manchester, Manchester M13 9PT, UK.
Stuart Pickering-BrownFaculty of Human and Medical Sciences, University of Manchester, Manchester M13 9PT, UK.
Richard W OrrellDepartment of Clinical Neuroscience, Institute of Neurology, University College London, London NW3 2PG, UK.
Katie C SidleDepartment of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square House, London WC1N 3BG, UK.
Andrea MalaspinaCentre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, NorthEast London and Essex Regional Motor Neuron Disease Care Centre, London E1 2AT, UK.
John HardyDepartment of Molecular Neuroscience and Reta Lila Weston Laboratories, Institute of Neurology, University College London, Queen Square House, London WC1N 3BG, UK.
Andrew B SingletonMolecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Janel O JohnsonNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Sampath ArepalliGenomics Technology Group, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Peter C SappDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Diane McKenna-YasekDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Meraida PolakDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Seneshaw AsressDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Safa Al-SarrajMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Andrew KingMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Claire TroakesMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Caroline VanceMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Jacqueline de BellerocheDivision of Brain Sciences, Department of Medicine, Imperial College London, London W120NN, UK.
Frank BaasDepartment of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Anneloor L M A Ten AsbroekDepartment of Neurogenetics and Neurology, Academic Medical Centre, Amsterdam, the Netherlands.
José Luis Muñoz-BlancoALS-Neuromuscular Unit, Hospital General Universitario Gregorio Marañón, IISGM, Madrid, Spain.
Dena G HernandezGenomics Technology Group, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Jinhui DingComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
J Raphael GibbsComputational Biology Group, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA.
Sonja W ScholzNeurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Mary Kay FloeterMotor Neuron Disorders Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Roy H CampbellDepartment of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Francesco LandiCenter for Geriatric Medicine, Department of Geriatrics, Neurosciences and Orthopedics, Catholic University of Sacred Heart, Rome 00168, Italy.
Robert BowserDivision of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
Stefan M PulstDepartment of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
John M RavitsDepartment of Neuroscience, University of California, San Diego, La Jolla, CA, USA.
Daniel J L MacGowanMount Sinai Beth Israel Hospital, Mount Sinai School of Medicine, New York, NY, USA.
Janine KirbySheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Erik P PioroDepartment of Neurology, Neuromuscular Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Roger PamphlettDiscipline of Pathology, Brain and Mind Centre, The University of Sydney, 94 Mallett Street, Camperdown, NSW 2050, Australia.
James BroachDepartment of Biochemistry, Penn State College of Medicine, Hershey, PA, USA.
Glenn GerhardDepartment of Pathology, Penn State College of Medicine, Hershey, PA, USA.
Travis L DunckleyNeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Christopher B BradyResearch and Development Service, Veterans Affairs Boston Healthcare System, Boston, MA, USA; Department of Neurology, Program in Behavioral Neuroscience, Boston University School of Medicine, Boston, MA, USA.
Neil W KowallNeurology Service, VA Boston Healthcare System and Boston University Alzheimer's Disease Center, Boston, MA 02130, USA.
Juan C TroncosoDepartments of Pathology and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Isabelle Le BerSorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et la Moelle (ICM), Assistance Publique Hôpitaux de Paris (AP-HP) - Hôpital Pitié-Salpêtrière, Paris, France.
Kevin MouzatINM, University Montpellier, Montpellier, France; Department of Biochemistry, CHU Nîmes, Nîmes, France.
Serge LumbrosoINM, University Montpellier, Montpellier, France; Department of Biochemistry, CHU Nîmes, Nîmes, France.
Terry D Heiman-PattersonDepartment of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA; Department of Neurology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Freya KamelEpidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
Ludo Van Den BoschKU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium; VIB, Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
Robert H BalohDepartment of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Tim M StromInstitute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Thomas MeitingerInstitute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Aleksey ShatunovMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Kristel R Van EijkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Mamede de CarvalhoInstitute of Physiology, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Department of Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
Maarten KooymanSURFsara, Amsterdam, the Netherlands.
Bas MiddelkoopDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Matthieu MoisseKU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium; VIB, Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium.
Russell L McLaughlinPopulation Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Republic of Ireland.
Michael A Van EsDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Markus WeberNeuromuscular Diseases Center/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Kevin B BoylanDepartment of Neurology, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Marka Van BlitterswijkDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Karen E MorrisonFaculty of Medicine, University of Southampton, Southampton, UK.
A Nazli BasakSuna and Inan Kırac Foundation, Neurodegeneration Research Laboratory, Bogazici University, Istanbul, Turkey.
Jesús S MoraALS Unit/Neurology, Hospital San Rafael, Madrid, Spain.
Vivian E DroryDepartment of Neurology, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel.
Pamela J ShawSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Martin R TurnerNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Kevin TalbotNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Orla HardimanAcademic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Republic of Ireland.
Kelly L WilliamsCentre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Jennifer A FifitaCentre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Garth A NicholsonCentre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia; ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, NSW 2139, Australia.
Ian P BlairCentre for MND Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
Guy A RouleauMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada.
Jesús Esteban-PérezUnidad de ELA, Instituto de Investigación Hospital 12 de Octubre de Madrid, SERMAS, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U-723), Madrid, Spain.
Alberto García-RedondoUnidad de ELA, Instituto de Investigación Hospital 12 de Octubre de Madrid, SERMAS, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER U-723), Madrid, Spain.
Ammar Al-ChalabiMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Project MinE ALS Sequencing Consortium
Ekaterina RogaevaTanz Centre for Research of Neurodegenerative Diseases, Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada.
Lorne ZinmanDivision of Neurology, Department of Internal Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
Lyle W OstrowDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Nicholas J MaragakisDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Jeffrey D RothsteinDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Zachary SimmonsDepartment of Neurology, Penn State Hershey Medical Center, Hershey, PA, USA.
Johnathan Cooper-KnockSheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
Alexis BriceSorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du Cerveau et la Moelle (ICM), Assistance Publique Hôpitaux de Paris (AP-HP) - Hôpital Pitié-Salpêtrière, Paris, France.
Stephen A GoutmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Eva L FeldmanDepartment of Neurology, University of Michigan, Ann Arbor, MI, USA.
Summer B GibsonDepartment of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Franco TaroniUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan 20133, Italy.
Antonia RattiDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center - Università degli Studi di Milano, Milan 20122, Italy.
Cinzia GelleraUnit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico "Carlo Besta," Milan 20133, Italy.
Philip Van DammeKU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium; VIB, Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium; University Hospitals Leuven, Department of Neurology, Leuven, Belgium.
Wim RobberechtKU Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), B-3000 Leuven, Belgium; VIB, Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium; University Hospitals Leuven, Department of Neurology, Leuven, Belgium.
Pietro FrattaSobell Department of Motor Neuroscience and Movement Disorders, University College London, Institute of Neurology, London, UK.
Mario SabatelliCentro Clinico NeMO, Institute of Neurology, Catholic University, Largo F. Vito 1, 00168 Rome, Italy.
Christian LunettaNEuroMuscular Omnicenter (NEMO), Serena Onlus Foundation, Milan, Italy.
Albert C LudolphNeurology Department, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Peter M AndersenDepartment of Pharmacology and Clinical Neuroscience, Umeå University, Umeå SE-90185, Sweden.
Jochen H WeishauptNeurology Department, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
William CamuALS Center, CHU Gui de Chauliac, University of Montpellier, Montpellier, France.
John Q TrojanowskiDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Vivianna M Van DeerlinDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Robert H BrownDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Leonard H van den BergDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Jan H VeldinkDepartment of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Matthew B HarmsDepartment of Neurology, Columbia University, New York, NY 10032, USA.
Jonathan D GlassDepartment of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
David J StoneGenetics and Pharmacogenomics, MRL, Merck & Co., Inc., West Point, PA 19486, USA.
Pentti TienariDepartment of Neurology, Helsinki University Hospital and Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki FIN-02900, Finland.
Vincenzo SilaniDepartment of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center - Università degli Studi di Milano, Milan 20122, Italy.
Adriano Chiò"Rita Levi Montalcini" Department of Neuroscience, University of Turin, Turin, Italy; Neuroscience Institute of Torino, Turin 10124, Italy.
Christopher E ShawMaurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London SE5 9RS, UK.
Bryan J TraynorNeuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, NIH, Porter Neuroscience Research Center, Bethesda, MD 20892, USA; Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: bryan.traynor@nih.gov.
John E LandersDepartment of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: john.landers@umassmed.edu.
University Medical Center Utrecht · NLKing's College London · GBNational Institute on Aging · USUniversity of Massachusetts Chan Medical School · USJohns Hopkins University · USGladstone Institutes · USCedars-Sinai Medical Center · USEmory University · USUniversity of Milan · ITIRCCS Istituto Auxologico Italiano · ITSt. Jude Children's Research Hospital · USUniversità degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Siena · ITFondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity of Helsinki · FIUniversity of Utah · USWashington University in St. Louis · USUniversity of Miami · USVIB-KU Leuven Center for Brain & Disease Research · BEBoston University · US

Funding

'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6M
Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
Neuropathology CoreP30AG013846 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KOWALL, NEIL W. · 1996 to 2020
$29.1M
Uncovering new genes and disease modifiers for ALS and related disordersU54NS092091 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Michael Benatar · 2014 to 2026
$19.8M
Project 3: Neuropathology of the multi-proteinopathy of c9FTD/ALS.P01NS084974 · NINDS · MAYO CLINIC JACKSONVILLE · PI PETRUCELLI, LEONARD · 2014 to 2024
$17.6M
Genetic characterization of atypical parkinsonismZIANS003154 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI SCHOLZ, SONJA · 2016 to 2025
$15.4M
Neuron and Glial Cellular Signatures from Normal and Diseased iPS Cells-SupplementU54NS091046 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI FINKBEINER, STEVEN M, FRAENKEL, ERNEST · 2014 to 2020
$11.7M
Genome wide SNP analysis in Amyotrophic Lateral SclerosisZIAAG000933 · NIA · NATIONAL INSTITUTE ON AGING · PI TRAYNOR, BRYAN · 2009 to 2025
$9.8M
Identification of genes causative for familial ALS gene using exome sequencingR01NS073873 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LANDERS, JOHN E · 2011 to 2019
$4.6M
Genetic Discovery and Pathobiology of Frontotemporal Lobar Degeneration and Related TDP-43 ProteinopathiesR35NS097261 · NINDS · MAYO CLINIC JACKSONVILLE · PI RADEMAKERS, ROSA · 2017 to 2019
$2.9M
Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
HISPANIC SECONDARY STROKE PREVENTION INITIATIVER01MD009164 · NIMHD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN · 2014 to 2018
$1.9M
BLRD VA I01 BX002466Intramural NIH HHS Z01 AG000949Intramural NIH HHS ZIA AG000933Medical Research Council G0500289Medical Research Council G0600974Medical Research Council G0900688Medical Research Council MC_PC_17115Medical Research Council MR/K01014X/1Medical Research Council MR/L016397/1Medical Research Council MR/L021803/1Medical Research Council MR/L501529/1Medical Research Council MR/M008606/1Medical Research Council MR/R024804/1Motor Neurone Disease Association ALCHALABI-DOBSON/APR14/829-791Motor Neurone Disease Association FRATTA/JAN15/946-795Motor Neurone Disease Association MALASPINA/APR13/817-791Motor Neurone Disease Association MCLAUGHLIN/OCT15/957-799Motor Neurone Disease Association SHAW/APR15/933-794Motor Neurone Disease Association SHAW/NOV14/985-797Motor Neurone Disease Association SMITH/APR16/847-791Motor Neurone Disease Association SMITH/OCT16/888-792Motor Neurone Disease Association TURNER/JAN13/944-795Motor Neurone Disease Association TURNER/OCT18/989-797MRF_ MRF-060-0003-RG-SMITHNHLBI NIH HHS K25 HL121295NIA NIH HHS P01 AG017586NIA NIH HHS P30 AG013846NIA NIH HHS P50 AG005146NIEHS NIH HHS K23 ES027221NIMHD NIH HHS R01 MD009164NINDS NIH HHS P01 NS084974NINDS NIH HHS R01 NS061867NINDS NIH HHS R01 NS073873NINDS NIH HHS R35 NS097261NINDS NIH HHS R56 NS061867NINDS NIH HHS U54 NS091046NINDS NIH HHS U54 NS092091Wellcome Trust
6 · The paper itself

Abstract

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.

Indexed as

AdultAgedAged, 80 and overAmino Acid SequenceAmyotrophic Lateral SclerosisCohort StudiesFemaleGenome-Wide Association StudyHumansKinesinsLoss of Function MutationMaleMiddle AgedYoung AdultKIF5A protein, humanKinesinsALSaxonal transportcargoGWASKIF5AWESWGS

Identifiers

PMID29566793
PMCPMC5867896
OpenAlexW2790053519

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.