Frequency of loss of function variants in LRRK2 in Parkinson disease
Por:
Blauwendraat C., Reed X., Kia D.A., Gan-Or Z., Lesage S., Pihlstrøm L., Guerreiro R., Gibbs J.R., Sabir M., Ahmed S., Ding J., Alcalay R.N., Hassin-Baer S., Pittman A.M., Brooks J., Edsall C., Hernandez D.G., Chung S.J., Goldwurm S., Toft M., Schulte C., Bras J., Wood N.W., Brice A., Morris H.R., Scholz S.W., Nalls M.A., Singleton A.B., Cookson M.R., Gasser T., Sharma M., Simón-Sánchez J., Heutink P., Giri A., Brockmann K., Oertel W., Klein C., Mohamed F., Malard L., Elbaz A., Corti O., Drouet V., Corvol J.-C., Tesei S., Canesi M., Valente E.M., Petrucci S., Ginevrino M., Aasly J., Houlden H., Hardy J., Orr-Urtreger A., Giladi N., Ferreira J., Guedes L.C., Bouça-Machado R., Coelho M., Rosa M.M., Tolosa E., Fernandez R., Ezquerra M., Marti M.J., Krüger R., May P., Glaab E., Balling R., Agid Y., Anheim M., Bonnet A.-M., Borg M., Broussolle E., Damier P., Destée A., Dürr A., Durif F., Krack P., Klebe S., Lohmann E., Martinez M., Penet C., Pollak P., Rascol O., Tison F., Tranchant C., Vérin M., Viallet F., Vidailhet M., Noyce A.J., Kaiyrzhanov R., Middlehurst B., Tan M., Plun-Favreau H., Holmans P., Trabzuni D., Quinn J., Mok K.Y., Kinghorn K.J., Billingsley K., Lewis P., Lovering R., R'Bibo L., Manzoni C., Rizig M., Ryten M., Guelfi S., Escott-Price V., Chelban V., Foltynie T., Williams N., Shashakin C., Zharkinbekova N., Zholdybayeva E., Aitkulova A., Danjou F., Rizzu P., Bandres-Ciga S., Craig D.W., Faghri F., Van Keuren-Jensen K., Shulman J.M., Leonard H.L., Robak L., Lubbe S., Finkbeiner S., Mencacci N.E., Lungu C., Rouleau G.A., Van Hilten J.J., Marinus J., Botía J.A., Clarimón J., Pastor P., Zimprich A., Pihlstrom L., Koks S., Taba P.
Publicada:
1 ene 2018
Resumen:
IMPORTANCE Pathogenic variants in LRRK2 are a relatively common genetic cause of Parkinson disease (PD). Currently, the molecular mechanism underlying disease is unknown, and gain and loss of function (LOF) models of pathogenesis have been postulated. LRRK2 variants are reported to result in enhanced phosphorylation of substrates and increased cell death. However, the double knockout of Lrrk2 and its homologue Lrrk1 results in neurodegeneration in a mouse model, suggesting that disease may occur by LOF. Because LRRK2 inhibitors are currently in development as potential disease-modifying treatments in PD, it is critical to determine whether LOF variants in LRRK2 increase or decrease the risk of PD. OBJECTIVE To determine whether LRRK1 and LRRK2 LOF variants contribute to the risk of developing PD. DESIGN, SETTING, AND PARTICIPANTS To determine the prevailing mechanism of LRRK2-mediated disease in human populations, next-generation sequencing data from a large case-control cohort (>23 000 individuals) was analyzed for LOF variants in LRRK1 and LRRK2. Data were generated at 5 different sites and 5 different data sets, including cases with clinically diagnosed PD and neurologically normal control individuals. Data were collected from 2012 through 2017. MAIN OUTCOMES AND MEASURES Frequencies of LRRK1 and LRRK2 LOF variants present in the general population and compared between cases and controls. RESULTS Among 11 095 cases with PD and 12 615 controls, LRRK1 LOF variants were identified in 0.205%of cases and 0.139% of controls (odds ratio, 1.48; SE, 0.571; 95%CI, 0.45-4.44; P = .49) and LRRK2 LOF variants were found in 0.117%of cases and 0.087%of controls (odds ratio, 1.48; SE, 0.431; 95%CI, 0.63-3.50; P = .36). All association tests suggested lack of association between LRRK1 or LRRK2 variants and PD. Further analysis of lymphoblastoid cell lines from several heterozygous LOF variant carriers found that, as expected, LRRK2 protein levels are reduced by approximately half compared with wild-type alleles. CONCLUSIONS AND RELEVANCE Together these findings indicate that haploinsufficiency of LRRK1 or LRRK2 is neither a cause of nor protective against PD. Furthermore, these results suggest that kinase inhibition or allele-specific targeting of mutant LRRK2 remain viable therapeutic strategies in PD. © 2018 American Medical Association. All rights reserved.
Filiaciones:
Blauwendraat C.:
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
NIA, National Institute of Neurological Disorders and Stroke (NINDS), United States
Reed X.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Kia D.A.:
Department of Molecular Neurosciences, Institute of Neurology, University College London (UCL), London, United Kingdom
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
University College London (UCL), Genetics Institute, London, United Kingdom
Gan-Or Z.:
Department of Human Genetics, McGill University, Montréal, Quebec, Canada
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada
Lesage S.:
Institut National de la Santé et de la Recherche Medicale U1127, Centre National de la Recherche Scientifique-Unité Mixte de Recherché (UMR) 7225, Sorbonne Universites, Université Pierre-et-Marie-Curie, University of Paris 06, UMR S1127, Institut du Cerveau et de la Moelle Épinière, Paris, F-75013, France
ICM INSERM U1127, Paris, France
ICM, INSERM U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S1127, CIC Pitié Neurosciences 1422, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
Pihlstrøm L.:
Department of Neurology, Oslo University Hospital, Oslo, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Guerreiro R.:
Dementia Research Institute, UCL, London, United Kingdom
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Department of Medical Sciences, Institute for Research in Biomedicine, University of Aveiro, Aveiro, Portugal
Gibbs J.R.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Sabir M.:
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Ahmed S.:
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Ding J.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Alcalay R.N.:
Department of Neurology, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, United States
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, United States
Hassin-Baer S.:
Movement Disorders Institute, Department of Neurology, Sagol Neuroscience Center, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, 5262101, Israel
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Pittman A.M.:
Department of Molecular Neurosciences, Institute of Neurology, University College London (UCL), London, United Kingdom
Brooks J.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Edsall C.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Hernandez D.G.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Chung S.J.:
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Goldwurm S.:
Parkinson Institute of Milan, Azienda Socio Sanitaria Territoriale Gaetano Pini/CTO, Milano, Italy
Department of Neuroscience, Rita Levi Montalcini, University of Turin, Turin, Italy
Toft M.:
Department of Neurology, Oslo University Hospital, Oslo, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Schulte C.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Bras J.:
Dementia Research Institute, UCL, London, United Kingdom
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Department of Medical Sciences, Institute for Research in Biomedicine, University of Aveiro, Aveiro, Portugal
Wood N.W.:
Department of Molecular Neurosciences, Institute of Neurology, University College London (UCL), London, United Kingdom
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
University College London (UCL), Genetics Institute, London, United Kingdom
Brice A.:
Institut National de la Santé et de la Recherche Medicale U1127, Centre National de la Recherche Scientifique-Unité Mixte de Recherché (UMR) 7225, Sorbonne Universites, Université Pierre-et-Marie-Curie, University of Paris 06, UMR S1127, Institut du Cerveau et de la Moelle Épinière, Paris, F-75013, France
Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Neurologie and Centre d'Investigation Clinique (CIC), Hôpital de la Pitié Salpêtrière, Paris, F-75013, France
Department of Genetics, Cytogenetics and Embryology, Pitié-Salpêtrière Hospital, Paris, France
ICM, INSERM U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S1127, CIC Pitié Neurosciences 1422, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
Morris H.R.:
Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom
Scholz S.W.:
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, United States
Nalls M.A.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Data Tecnica International, Glen Echo, MD, United States
Singleton A.B.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Cookson M.R.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Gasser T.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Sharma M.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany
Simón-Sánchez J.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Heutink P.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Hertie Institute for Clinical Brain Research, Tübingen, Germany
Giri A.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Brockmann K.:
Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Oertel W.:
University Hospital Marburg, University of Marburg, Marburg, Germany
Klein C.:
Institute of Neurogenetics, University of Lübeck, University Hospital of Schleswig-Holstein, Lübeck, Germany
Mohamed F.:
Université Paris-Saclay, Université Paris-Sud, Université de Versailles Saint-Quentinen-Yvelines (UVSQ), Center for Research in Epidemiology and Population Health (CESP), Institut National de la Santé et de la Recherche Medicale (INSERM), Villejuif, France
Malard L.:
Université Paris-Saclay, Université Paris-Sud, Université de Versailles Saint-Quentinen-Yvelines (UVSQ), Center for Research in Epidemiology and Population Health (CESP), Institut National de la Santé et de la Recherche Medicale (INSERM), Villejuif, France
Elbaz A.:
Université Paris-Saclay, Université Paris-Sud, Université de Versailles Saint-Quentinen-Yvelines (UVSQ), Center for Research in Epidemiology and Population Health (CESP), Institut National de la Santé et de la Recherche Medicale (INSERM), Villejuif, France
Corti O.:
Institut National de la Santé et de la Recherche Medicale U1127, Centre National de la Recherche Scientifique-Unité Mixte de Recherché (UMR) 7225, Sorbonne Universites, Université Pierre-et-Marie-Curie, University of Paris 06, UMR S1127, Institut du Cerveau et de la Moelle Épinière, Paris, F-75013, France
Drouet V.:
Institut National de la Santé et de la Recherche Medicale U1127, Centre National de la Recherche Scientifique-Unité Mixte de Recherché (UMR) 7225, Sorbonne Universites, Université Pierre-et-Marie-Curie, University of Paris 06, UMR S1127, Institut du Cerveau et de la Moelle Épinière, Paris, F-75013, France
Corvol J.-C.:
Institut National de la Santé et de la Recherche Medicale U1127, Centre National de la Recherche Scientifique-Unité Mixte de Recherché (UMR) 7225, Sorbonne Universites, Université Pierre-et-Marie-Curie, University of Paris 06, UMR S1127, Institut du Cerveau et de la Moelle Épinière, Paris, F-75013, France
Assistance Publique-Hôpitaux de Paris (AP-HP), Département de Neurologie and Centre d'Investigation Clinique (CIC), Hôpital de la Pitié Salpêtrière, Paris, F-75013, France
Centre for Clinical Investigations, Paris, France
ICM, INSERM U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S1127, CIC Pitié Neurosciences 1422, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
Tesei S.:
Parkinson Institute of Milan, Azienda Socio Sanitaria Territoriale Gaetano Pini/CTO, Milano, Italy
Canesi M.:
Parkinson Institute of Milan, Azienda Socio Sanitaria Territoriale Gaetano Pini/CTO, Milano, Italy
Valente E.M.:
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Neurogenetics Laboratory, Istituto di Ricovero e Cura A Carattere Scientifico (IRCCS), Santa Lucia Foundation, Rome, Italy
Petrucci S.:
Neurogenetics Laboratory, Istituto di Ricovero e Cura A Carattere Scientifico (IRCCS), Santa Lucia Foundation, Rome, Italy
Department of Neurological Sciences, Sapienza University, Rome, Italy
Ginevrino M.:
Department of Molecular Medicine, University of Pavia, Pavia, Italy
Neurogenetics Laboratory, Istituto di Ricovero e Cura A Carattere Scientifico (IRCCS), Santa Lucia Foundation, Rome, Italy
Aasly J.:
Department of Neurology, St Olav's Hospital and Norwegian University of Science and Technology, Trondheim, Norway
Houlden H.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Hardy J.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Orr-Urtreger A.:
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Giladi N.:
Center for Neurodegeneration, Neurological Institute, Sackler School of Medicine, Sagol School for Neuroscience, Tel Aviv University, Israel
Ferreira J.:
Neurological Clinical Research Unit, Instituto de Medicina Molecular, Lisbon, Portugal
Guedes L.C.:
Neurology Service, Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Bouça-Machado R.:
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Coelho M.:
Neurology Service, Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Rosa M.M.:
Neurology Service, Department of Neurosciences, Hospital de Santa Maria, Lisbon, Portugal
Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal
Tolosa E.:
Neurology Service, Hospital Clínic, Department of Neurology, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Barcelona, Spain
Fernandez R.:
Neurology Service, Hospital Clínic, Department of Neurology, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Barcelona, Spain
Ezquerra M.:
Neurology Service, Hospital Clínic, Department of Neurology, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Barcelona, Spain
Marti M.J.:
Neurology Service, Hospital Clínic, Department of Neurology, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Barcelona, Spain
Krüger R.:
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
May P.:
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
Glaab E.:
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
Balling R.:
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Luxembourg, Luxembourg
Agid Y.:
Department for the Central Nervous System, UPMC, Paris, France
Anheim M.:
Centre de Reference des Maladies Neurogenetiques de l'Enfant et de l'Adulte, Paris, France
Bonnet A.-M.:
Department for the Central Nervous System, UPMC, Paris, France
Borg M.:
Department of Clinical Neurosciences (Movement Disorders), Nice University Hospital, Nice, France
Broussolle E.:
Pôle des Spécialités Neurologiques, Lyon, France
Damier P.:
Department of Neurology, Centre Hospitalier Universitaire de Nantes, Nantes, France
Destée A.:
Department of Neurology A, Centre Hospitalier Regional Universitaire de Lille, Lille, France
Dürr A.:
Department of Genetics and Cytogenetics, Pitié-Salpêtrière Hospital, Paris, France
Durif F.:
Department of Neurology A, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
Krack P.:
Pôle Psychiatrie et Neurologie, Grenoble, France
Klebe S.:
Centre for Clinical Investigations, Paris, France
Lohmann E.:
Department of Genetics and Cytogenetics, Pitié-Salpêtrière Hospital, Paris, France
Martinez M.:
INSERM Unit 563, Toulouse, France
INSERM UMR 1220, Paul Sabatier University, Toulouse, France
Penet C.:
ICM INSERM U1127, DNA and Cell Bank, Paris, France
Pollak P.:
Pôle Psychiatrie et Neurologie, Grenoble, France
Rascol O.:
Clinical Investigation Centre, Toulouse, France
Tison F.:
Pôle des Neurosciences, Cliniques de Neurologie, Pessac, France
Tranchant C.:
Department of Neurology, Centre Hospitalier Universitaire de Strasbourg, Strasbourg, France
Vérin M.:
Department of Neurology, Centre Hospitalier Universitaire Pontchaillou, Rennes, France
Viallet F.:
Department of Neurology, Hôpital d'Aix en Provence, Aix-en-Provence, France
Vidailhet M.:
Department for the Central Nervous System, UPMC, Paris, France
Noyce A.J.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, Queen Mary University of London (QMUL), London, United Kingdom
Kaiyrzhanov R.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Middlehurst B.:
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Tan M.:
Department of Clinical Neuroscience, UCL Institute of Neurology, London, United Kingdom
Plun-Favreau H.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Holmans P.:
Biostatistics and Bioinformatics Unit, Institute of Psychological Medicine and Clinical Neuroscience, MRC (Medical Research Council) Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom
Trabzuni D.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
Quinn J.:
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Mok K.Y.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
Kinghorn K.J.:
Institute of Healthy Ageing, UCL, United Kingdom
UCL, United Kingdom
Billingsley K.:
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Lewis P.:
University of Reading, Reading, United Kingdom
Lovering R.:
UCL, United Kingdom
R'Bibo L.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Manzoni C.:
University of Reading, Reading, United Kingdom
Rizig M.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Ryten M.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Guelfi S.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Escott-Price V.:
MRC Centre for Neuropsychiatric Genetics and Genomics, Dementia Research Institute, Cardiff University School of Medicine, Cardiff, United Kingdom
Chelban V.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Foltynie T.:
UCL Institute of Neurology, United Kingdom
Williams N.:
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, United Kingdom
Shashakin C.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Zharkinbekova N.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Zholdybayeva E.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Aitkulova A.:
Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom
Danjou F.:
ICM, INSERM U 1127, CNRS, UMR 7225, Sorbonne Universités, UPMC University Paris 06, UMR S1127, CIC Pitié Neurosciences 1422, AP-HP, Pitié-Salpêtrière Hospital, Paris, France
Rizzu P.:
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
Bandres-Ciga S.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Craig D.W.:
Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, United States
Faghri F.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana-Champaign, United States
Van Keuren-Jensen K.:
Neurogenomics Division, TGen, Phoenix, Arizona, United States
Shulman J.M.:
Departments of Neurology, Neuroscience, and Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States
Leonard H.L.:
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
Robak L.:
Baylor College of Medicine, Houston, United States
Lubbe S.:
Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Finkbeiner S.:
Departments of Neurology and Physiology, University of California, San Francisco, United States
Gladstone Institute of Neurological Disease, Taube/Koret Center for Neurodegenerative Disease Research, San Francisco, United States
Mencacci N.E.:
Northwestern University Feinberg School of Medicine, United States
Lungu C.:
National Institutes of Health Division of Clinical Research, NINDS, NIH, United States
Rouleau G.A.:
Montreal Neurological Institute and Hospital, Department of Neurology and Neurosurgery, McGill University, Canada
Van Hilten J.J.:
Department of Neurology, Leiden University Medical Center, Leiden, Netherlands
Marinus J.:
Department of Neurology, Leiden University Medical Center, Leiden, Netherlands
Botía J.A.:
Universidad de Murcia, Murcia, Spain
Clarimón J.:
Memory Unit, Department of Neurology, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, CIBERNED, Madrid, Spain
Pastor P.:
Fundació Docència i Recerca Mútua de Terrassa and Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain
Zimprich A.:
Department of Neurology, Medical University of Vienna, Austria
Pihlstrom L.:
Department of Neurology, Oslo University Hospital, Oslo, Norway
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Koks S.:
Department of Pathophysiology, University of Tartu, Tartu, Estonia
Department of Reproductive Biology, Estonian University of Life Sciences, Tartu, Estonia
Taba P.:
Department of Neurology and Neurosurgery, University of Tartu, Estonia
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