title: Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rheenen
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Shatunov
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Annelot M
authors.initials: AM
authors.lastname: Dekker
authors.affiliation: Population Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Russell L
authors.initials: RL
authors.lastname: McLaughlin
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Diekstra
authors.affiliation: Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pulit
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Rick A A
authors.initials: RA
authors.lastname: van der Spek
authors.affiliation: Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors.forename: Urmo
authors.initials: U
authors.lastname: Võsa
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: de Jong
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Robinson
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Jian
authors.identifier: 0000-0003-2001-2474
authors.initials: J
authors.lastname: Yang
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.|Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Fogh
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Perry Tc
authors.initials: PT
authors.lastname: van Doormaal
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Gijs H P
authors.initials: GH
authors.lastname: Tazelaar
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Koppers
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blokhuis
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: William
authors.identifier: 0000-0002-9335-9260
authors.initials: W
authors.lastname: Sproviero
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Jones
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Kenna
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Kristel R
authors.initials: KR
authors.lastname: van Eijk
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Harschnitz
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Raymond D
authors.initials: RD
authors.lastname: Schellevis
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: William J
authors.identifier: 0000-0002-7134-7584
authors.initials: WJ
authors.lastname: Brands
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jelena
authors.initials: J
authors.lastname: Medic
authors.affiliation: Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Androniki
authors.initials: A
authors.lastname: Menelaou
authors.affiliation: Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.|Department of Neurology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Alice
authors.initials: A
authors.lastname: Vajda
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Pathophysiology and Tranplantation, 'Dino Ferrari' Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Kuang
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.|Biomedical Research Institute BRIS, Ljubljana, Slovenia.
authors.forename: Boris
authors.identifier: 0000-0003-3898-1943
authors.initials: B
authors.lastname: Rogelj
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Vrabec
authors.affiliation: Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.|Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Metka
authors.initials: M
authors.lastname: Ravnik-Glavač
authors.affiliation: Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Blaž
authors.identifier: 0000-0002-5083-8261
authors.initials: B
authors.lastname: Koritnik
authors.affiliation: Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Zidar
authors.affiliation: Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Leonardis
authors.affiliation: Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Leja Dolenc
authors.initials: LD
authors.lastname: Grošelj
authors.affiliation: Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06, UMRS 1127, Paris, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Millecamps
authors.affiliation: Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06, UMRS 1127, Paris, France.|Centre de Référence Maladies Rares SLA Ile de France, Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Paris, France.|GRC-UPMC SLA et Maladies du Motoneurone, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Salachas
authors.affiliation: Ramsay Generale de Santé, Hôpital Peupliers, Paris, France.|Réseau SLA Ile de France, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.affiliation: Institute of Physiology, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.|Department of Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
authors.affiliation: Institute of Physiology, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.|Department of Neurosciences, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Department of Neurology, Hospital San Rafael, Madrid, Spain.
authors.forename: Jesus S
authors.initials: JS
authors.lastname: Mora
authors.affiliation: Neurology Department, Hospital de la Santa Creu i Sant Pau de Barcelona, Autonomous University of Barcelona, Barcelona, Spain.|Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rojas-García
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.|Emory ALS Center, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Meraida
authors.initials: M
authors.lastname: Polak
authors.affiliation: Euan MacDonald Centre for Motor Neuron Disease Research, Edinburgh, UK.|Centre for Neuroregeneration and Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Siddharthan
authors.initials: S
authors.lastname: Chandran
authors.affiliation: Euan MacDonald Centre for Motor Neuron Disease Research, Edinburgh, UK.
authors.forename: Shuna
authors.initials: S
authors.lastname: Colville
authors.affiliation: Euan MacDonald Centre for Motor Neuron Disease Research, Edinburgh, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Swingler
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Morrison
authors.affiliation: Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Clinical Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Orrell
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.|Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Pittman
authors.affiliation: Department of Clinical Neuroscience, Institute of Neurology, University College London, London, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Sidle
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK.
authors.forename: Pietro
authors.initials: P
authors.lastname: Fratta
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK.|North-East London and Essex Regional Motor Neuron Disease Care Centre, London, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Simon
authors.identifier: 0000-0002-5200-3284
authors.initials: S
authors.lastname: Topp
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
authors.affiliation: Department of Neurology, Otto von Güricke University Magdeburg, Magdeburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Abdulla
authors.affiliation: Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Drepper
authors.affiliation: Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sendtner
authors.affiliation: Department of Neurology, Charité University Hospital, Humboldt University, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.affiliation: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Roel A
authors.initials: RA
authors.lastname: Ophoff
authors.affiliation: Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Staats
authors.affiliation: Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Wiedau-Pazos
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lomen-Hoerth
authors.affiliation: Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Vivianna M
authors.identifier: 0000-0002-7400-9097
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Elman
authors.affiliation: Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Leo
authors.initials: L
authors.lastname: McCluskey
authors.affiliation: Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey.
authors.forename: A Nazli
authors.initials: AN
authors.lastname: Basak
authors.affiliation: Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey.
authors.forename: Ceren
authors.initials: C
authors.lastname: Tunca
authors.affiliation: Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey.
authors.forename: Hamid
authors.initials: H
authors.lastname: Hamzeiy
authors.affiliation: Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Parman
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.affiliation: Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Milena
authors.initials: M
authors.lastname: Radivojkov-Blagojevic
authors.affiliation: INSERM U930, Université François Rabelais, Tours, France.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.affiliation: INSERM U930, Université François Rabelais, Tours, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Maurel
authors.affiliation: AP-HP, Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, Paris, France.|UPMC, Pharmacologie, Paris VI, Paris, France.|BESPIM, CHU de Nîmes, Nîmes, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bensimon
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Landwehrmeyer
authors.affiliation: INSERM U1127, Hôpital de la Pitié-Salpêtrière, Paris, France.|CNRS UMR 7225, Hôpital de la Pitié-Salpêtrière, Paris, France.|Sorbonne Universités, UPMC Paris 06, UMRS 1127, Hôpital de la Pitié-Salpêtrière, Paris, France.|Institut du Cerveau et de la Moelle Epinière, Hôpital de la Pitié-Salpêtrière, Paris, France.|AP-HP, Département de Génétique, Hôpital de la Pitié-Salpêtrière, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: AP-HP, Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, Paris, France.|BESPIM, CHU de Nîmes, Nîmes, France.
authors.forename: Christine A M
authors.initials: CA
authors.lastname: Payan
authors.affiliation: Genethon, CNRS UMR 8587, Evry, France.
authors.forename: Safaa
authors.initials: S
authors.lastname: Saker-Delye
authors.affiliation: Department of Medical Genetics, Institut du Cerveau et de la Moelle Epinière, Hôptial Pitié-Salpêtrière, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dürr
authors.affiliation: Department of Neurogenetics, Institute of Neurology, University College London, London, UK.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.affiliation: PopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Tittmann
authors.affiliation: PopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life and Brain Center, Bonn, Germany.|Division of Medical Genetics, University Hospital Basel, University of Basel, Basel, Switzerland.|Department of Biomedicine, University of Basel, Basel, Switzerland.|Institute of Neuroscience and Medicine INM-1, Research Center Juelich, Juelich, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany.|Department of Genomics, Life and Brain Center, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: University of Lille, INSERM, CHU de Lille, Institut Pasteur de Lille, U1167-RID-AGE Risk Factor and Molecular Determinants of Aging Diseases, Lille, France.
authors.forename: Philippe
authors.identifier: 0000-0001-9088-234X
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: Bordeaux University, ISPED, Centre INSERM U1219-Epidemiologie Biostatistique et CIC-1401, CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tzourio
authors.affiliation: Bordeaux University, ISPED, Centre INSERM U1219-Epidemiologie Biostatistique et CIC-1401, CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dartigues
authors.affiliation: Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Fernando
authors.identifier: 0000-0001-9435-9441
authors.initials: F
authors.lastname: Rivadeneira
authors.affiliation: Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Karol
authors.initials: K
authors.lastname: Estrada
authors.affiliation: Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Curtis
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Hylke M
authors.initials: HM
authors.lastname: Blauw
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.affiliation: Department of Neurosciences, Experimental Neurology, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven-University of Leuven, Leuven, Belgium.
authors.forename: An
authors.identifier: 0000-0002-1276-6682
authors.initials: A
authors.lastname: Goris
authors.affiliation: Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Shaw
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Bradley N
authors.initials: BN
authors.lastname: Smith
authors.affiliation: Laboratory of Experimental Neurobiology, IRCCS 'C. Mondino' National Institute of Neurology Foundation, Pavia, Italy.
authors.forename: Orietta
authors.initials: O
authors.lastname: Pansarasa
authors.affiliation: Laboratory of Experimental Neurobiology, IRCCS 'C. Mondino' National Institute of Neurology Foundation, Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.affiliation: Neurologic Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.affiliation: Neurologic Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.affiliation: Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: D'Alfonso
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bertolin
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Sorarù
authors.affiliation: Department of Neurology, Università del Piemonte Orientale, Novara, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Mazzini
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Pensato
authors.affiliation: Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Gellera
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tiloca
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Pathophysiology and Tranplantation, 'Dino Ferrari' Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ratti
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.|Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.|Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.|Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.affiliation: Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Arcuti
authors.affiliation: Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Capozzo
authors.affiliation: Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Zecca
authors.affiliation: NEMO Clinical Center, Serena Onlus Foundation, Niguarda Ca' Granda Hostipal, Milan, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Penco
authors.affiliation: Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.affiliation: Project MinE Foundation, Rotterdam, the Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Muller
authors.affiliation: Project MinE Foundation, Rotterdam, the Netherlands.
authors.forename: Robbert Jan
authors.initials: RJ
authors.lastname: Stuit
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Blair
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Katharine
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Emily P
authors.initials: EP
authors.lastname: McCann
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Fifita
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.|University of Sydney, ANZAC Research Institute, Concord Hospital, Sydney, New South Wales, Australia.
authors.forename: Garth A
authors.initials: GA
authors.lastname: Nicholson
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Dominic B
authors.initials: DB
authors.lastname: Rowe
authors.affiliation: Stacey MND Laboratory, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Roger
authors.identifier: 0000-0003-3326-7273
authors.initials: R
authors.lastname: Pamphlett
authors.affiliation: Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Kiernan
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Grosskreutz
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ringer
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Tino
authors.initials: T
authors.lastname: Prell
authors.affiliation: Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Stubendorff
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Ingo
authors.identifier: 0000-0002-5642-8378
authors.initials: I
authors.lastname: Kurth
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Jena, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Department of Neurology, Brighton and Sussex Medical School Trafford Centre for Biomedical Research, University of Sussex, Falmer, UK.
authors.forename: P Nigel
authors.initials: PN
authors.lastname: Leigh
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Casale
authors.affiliation: 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.|Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Chio
authors.affiliation: Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
authors.affiliation: Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pupillo
authors.affiliation: Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tortelli
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.|Unit of Neurodegenerative Diseases, Department of Clinical Research in Neurology, University of Bari 'Aldo Moro' at Pia Fondazione Cardinale G. Panico, Tricase, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Weishaupt
authors.affiliation: Department of Neurosciences, Experimental Neurology, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven-University of Leuven, Leuven, Belgium.|Vesalius Research Center, Laboratory of Neurobiology, VIB, Leuven, Belgium.|Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.affiliation: Department of Neurosciences, Experimental Neurology, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven-University of Leuven, Leuven, Belgium.|Vesalius Research Center, Laboratory of Neurobiology, VIB, Leuven, Belgium.|Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.affiliation: Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors.forename: Lude
authors.identifier: 0000-0002-5159-8802
authors.initials: L
authors.lastname: Franke
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.|Division of Genetics, Boston Children's Hospital, Boston, Massachusetts, USA.|Center for Basic Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: Tune H
authors.initials: TH
authors.lastname: Pers
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.|Emory ALS Center, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Landers
authors.affiliation: Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.|Department of Neurology, Beaumont Hospital, Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.|Department of Pharmacology and Clinical Neurosience, Umeå University, Umeå, Sweden.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Andersen
authors.affiliation: INSERM U930, Université François Rabelais, Tours, France.|Centre SLA, CHRU de Tours, Tours, France.|Federation des Centres SLA Tours and Limoges, LITORALS, Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.affiliation: INSERM U930, Université François Rabelais, Tours, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.|Department of Pathophysiology and Tranplantation, 'Dino Ferrari' Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Naomi R
authors.identifier: 0000-0001-7421-3357
authors.initials: NR
authors.lastname: Wray
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.|Diamantina Institute, University of Queensland Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Peter M
authors.identifier: 0000-0002-2143-8760
authors.initials: PM
authors.lastname: Visscher
authors.affiliation: Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.|Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Michael A
authors.initials: MA
authors.lastname: van Es
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: R Jeroen
authors.identifier: 0000-0003-1631-6440
authors.initials: RJ
authors.lastname: Pasterkamp
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Medical and Molecular Genetics, King's College London, London, UK.
authors.forename: Cathryn M
authors.identifier: 0000-0002-8249-8476
authors.initials: CM
authors.lastname: Lewis
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|NIHR Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.affiliation: Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK.
authors.forename: Ammar
authors.initials: A
authors.lastname: Al-Chalabi
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
authors.affiliation: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Veldink
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D051938:Munc18 Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009185:Myelin Proteins / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D011506:Proteins / Q000235:genetics*
chemical_list: C111475:CFAP410 protein, human; D003598:Cytoskeletal Proteins; C560487:MOBP protein, human; D051938:Munc18 Proteins; D009185:Myelin Proteins; D011506:Proteins