Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis.

Autor: van Rheenen W; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Shatunov A; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Dekker AM; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., McLaughlin RL; Population Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland., Diekstra FP; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Pulit SL; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands., van der Spek RA; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Võsa U; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands., de Jong S; 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., Robinson MR; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Yang J; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Fogh I; 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., van Doormaal PT; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Tazelaar GH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Koppers M; 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., Blokhuis AM; 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., Sproviero W; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Jones AR; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Kenna KP; Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., van Eijk KR; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Harschnitz O; 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., Schellevis RD; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Brands WJ; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Medic J; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Menelaou A; Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands., Vajda A; Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.; Department of Neurology, Beaumont Hospital, Dublin, Ireland., Ticozzi N; 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., Lin K; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Rogelj B; Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia.; Biomedical Research Institute BRIS, Ljubljana, Slovenia., Vrabec K; Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Ravnik-Glavač M; 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., Koritnik B; Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia., Zidar J; Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia., Leonardis L; Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia., Grošelj LD; Ljubljana ALS Centre, Institute of Clinical Neurophysiology, University Medical Centre Ljubljana, Ljubljana, Slovenia., Millecamps S; Institut du Cerveau et de la Moelle Epinière, INSERM U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06, UMRS 1127, Paris, France., Salachas F; 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., Meininger V; Ramsay Generale de Santé, Hôpital Peupliers, Paris, France.; Réseau SLA Ile de France, Paris, France., de Carvalho M; 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., Pinto S; 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., Mora JS; Department of Neurology, Hospital San Rafael, Madrid, Spain., Rojas-García R; 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., Polak M; Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.; Emory ALS Center, Emory University School of Medicine, Atlanta, Georgia, USA., Chandran S; 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., Colville S; Euan MacDonald Centre for Motor Neuron Disease Research, Edinburgh, UK., Swingler R; Euan MacDonald Centre for Motor Neuron Disease Research, Edinburgh, UK., Morrison KE; Faculty of Medicine, University of Southampton, Southampton, UK., Shaw PJ; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK., Hardy J; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK., Orrell RW; Department of Clinical Neuroscience, Institute of Neurology, University College London, London, UK., Pittman A; Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.; Reta Lila Weston Institute, Institute of Neurology, University College London, London, UK., Sidle K; Department of Clinical Neuroscience, Institute of Neurology, University College London, London, UK., Fratta P; Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK., Malaspina A; 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., Topp S; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Petri S; Department of Neurology, Hannover Medical School, Hannover, Germany., Abdulla S; Department of Neurology, Otto von Güricke University Magdeburg, Magdeburg, Germany., Drepper C; Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany., Sendtner M; Institute of Clinical Neurobiology, University Hospital Würzburg, Würzburg, Germany., Meyer T; Department of Neurology, Charité University Hospital, Humboldt University, Berlin, Germany., Ophoff RA; 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., Staats KA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, California, USA., Wiedau-Pazos M; Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA., Lomen-Hoerth C; Department of Neurology, University of California, San Francisco, San Francisco, California, USA., Van Deerlin VM; Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Trojanowski JQ; Center for Neurodegenerative Disease Research, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Elman L; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., McCluskey L; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA., Basak AN; Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey., Tunca C; Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey., Hamzeiy H; Neurodegeneration Research Laboratory, Bo[gcaron]aziçi University, Istanbul, Turkey., Parman Y; Neurology Department, Istanbul Medical School, Istanbul University, Istanbul, Turkey., Meitinger T; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Lichtner P; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Radivojkov-Blagojevic M; Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany., Andres CR; INSERM U930, Université François Rabelais, Tours, France., Maurel C; INSERM U930, Université François Rabelais, Tours, France., Bensimon G; 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., Landwehrmeyer B; Department of Neurology, Ulm University, Ulm, Germany., Brice A; 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., Payan CA; AP-HP, Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, Paris, France.; BESPIM, CHU de Nîmes, Nîmes, France., Saker-Delye S; Genethon, CNRS UMR 8587, Evry, France., Dürr A; Department of Medical Genetics, Institut du Cerveau et de la Moelle Epinière, Hôptial Pitié-Salpêtrière, Paris, France., Wood NW; Department of Neurogenetics, Institute of Neurology, University College London, London, UK., Tittmann L; PopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany., Lieb W; PopGen Biobank and Institute of Epidemiology, Christian Albrechts University Kiel, Kiel, Germany., Franke A; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany., Rietschel M; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Heidelberg, Germany., Cichon S; 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., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Department of Genomics, Life and Brain Center, Bonn, Germany., Amouyel P; University of Lille, INSERM, CHU de Lille, Institut Pasteur de Lille, U1167-RID-AGE Risk Factor and Molecular Determinants of Aging Diseases, Lille, France., Tzourio C; Bordeaux University, ISPED, Centre INSERM U1219-Epidemiologie Biostatistique et CIC-1401, CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France., Dartigues JF; Bordeaux University, ISPED, Centre INSERM U1219-Epidemiologie Biostatistique et CIC-1401, CHU de Bordeaux, Pôle de Santé Publique, Bordeaux, France., Uitterlinden AG; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands., Rivadeneira F; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands., Estrada K; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands., Hofman A; Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Curtis C; 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., Blauw HM; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., van der Kooi AJ; Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands., de Visser M; Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Goris A; Department of Neurosciences, Experimental Neurology, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven-University of Leuven, Leuven, Belgium., Weber M; Neuromuscular Diseases Unit/ALS Clinic, Kantonsspital St. Gallen, St. Gallen, Switzerland., Shaw CE; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Smith BN; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Pansarasa O; Laboratory of Experimental Neurobiology, IRCCS 'C. Mondino' National Institute of Neurology Foundation, Pavia, Italy., Cereda C; Laboratory of Experimental Neurobiology, IRCCS 'C. Mondino' National Institute of Neurology Foundation, Pavia, Italy., Del Bo R; Neurologic Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Comi GP; Neurologic Unit, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., D'Alfonso S; Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases, Università del Piemonte Orientale, Novara, Italy., Bertolin C; Department of Neurosciences, University of Padova, Padova, Italy., Sorarù G; Department of Neurosciences, University of Padova, Padova, Italy., Mazzini L; Department of Neurology, Università del Piemonte Orientale, Novara, Italy., Pensato V; Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy., Gellera C; Unit of Genetics of Neurodegenerative and Metabolic Diseases, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', Milan, Italy., Tiloca C; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy., Ratti A; 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., Calvo A; 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.; Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy., Moglia C; 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.; Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy., Brunetti M; 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.; Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy., Arcuti S; Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy., Capozzo R; Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy., Zecca C; Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy., Lunetta C; NEMO Clinical Center, Serena Onlus Foundation, Niguarda Ca' Granda Hostipal, Milan, Italy., Penco S; Medical Genetics Unit, Department of Laboratory Medicine, Niguarda Ca' Granda Hospital, Milan, Italy., Riva N; Department of Neurology, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy., Padovani A; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy., Filosto M; Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy., Muller B; Project MinE Foundation, Rotterdam, the Netherlands., Stuit RJ; Project MinE Foundation, Rotterdam, the Netherlands., Blair I; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia., Zhang K; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia., McCann EP; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia., Fifita JA; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia., Nicholson GA; 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., Rowe DB; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia., Pamphlett R; Stacey MND Laboratory, Department of Pathology, University of Sydney, Sydney, New South Wales, Australia., Kiernan MC; Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia., Grosskreutz J; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany., Witte OW; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany., Ringer T; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany., Prell T; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany., Stubendorff B; Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany., Kurth I; Institute of Human Genetics, Jena University Hospital, Jena, Germany., Hübner CA; Institute of Human Genetics, Jena University Hospital, Jena, Germany., Leigh PN; Department of Neurology, Brighton and Sussex Medical School Trafford Centre for Biomedical Research, University of Sussex, Falmer, UK., Casale F; 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy., Chio A; 'Rita Levi Montalcini' Department of Neuroscience, ALS Centre, University of Torino, Turin, Italy.; Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy., Beghi E; Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy., Pupillo E; Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy., Tortelli R; Department of Clinical Research in Neurology, University of Bari 'A. Moro' at Pia Fondazione 'Card. G. Panico', Tricase, Italy., Logroscino G; 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., Powell J; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., Ludolph AC; Department of Neurology, Ulm University, Ulm, Germany., Weishaupt JH; Department of Neurology, Ulm University, Ulm, Germany., Robberecht W; 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., Van Damme P; 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., Franke L; Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands., Pers TH; 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., Brown RH; Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Glass JD; Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.; Emory ALS Center, Emory University School of Medicine, Atlanta, Georgia, USA., Landers JE; Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Hardiman O; Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin, Ireland.; Department of Neurology, Beaumont Hospital, Dublin, Ireland., Andersen PM; Department of Neurology, Ulm University, Ulm, Germany.; Department of Pharmacology and Clinical Neurosience, Umeå University, Umeå, Sweden., Corcia P; INSERM U930, Université François Rabelais, Tours, France.; Centre SLA, CHRU de Tours, Tours, France.; Federation des Centres SLA Tours and Limoges, LITORALS, Tours, France., Vourc'h P; INSERM U930, Université François Rabelais, Tours, France., Silani V; 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., Wray NR; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Visscher PM; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; Diamantina Institute, University of Queensland Translational Research Institute, Brisbane, Queensland, Australia., de Bakker PI; 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., van Es MA; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Pasterkamp RJ; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Lewis CM; 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., Breen G; 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., Al-Chalabi A; Maurice Wohl Clinical Neuroscience Institute, Department of Basic and Clinical Neuroscience, King's College London, London, UK., van den Berg LH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands., Veldink JH; Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2016 Sep; Vol. 48 (9), pp. 1043-8. Date of Electronic Publication: 2016 Jul 25.
DOI: 10.1038/ng.3622
Abstrakt: 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.
Databáze: MEDLINE