Rapidly advancing sequencing technologies offer new and cost-effective approaches to identify patients with hereditary neurological diseases. While studying small numbers of patients may suffice to elucidate the pathophysiology of a specific disease, establishing accurate genotype-phenotype and genotype-treatment relationships necessitates large sample sizes. This typically requires large multi-center approaches and poses a challenge to systematically and uniformly investigating patients. Meta-analyses and systematic reviews can serve as instruments to combine information from several small samples, but unfortunately, this is often complicated by inconsistent and incomplete reporting of clinical and genetic data.
Using genetic Parkinson’s disease (PD) as an example, and Illustrating the magnitude of the problem, up to ~300,000 patients worldwide are estimated to have hereditary forms of PD, representing 5% of an estimated total of 6 million patients with PD in 20181. Monogenic forms of Parkinson’s disease (PD) can be caused by mutations in SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ1 2, and in addition, GBA variants represent the strongest known genetic risk factor for PD, with an age-dependent penetrance of ~30% at the age of 80 years3. Clinical information for patients with genetic PD is, however, only reported for a fraction of cases (n=1,769, Pubmed and Movement Disorder Society Genetic mutation database; MDSGene, www.mdsgene.org) in the international medical literature and publications often focus on unusual presentations. Both clinical expression and penetrance of gene mutations may vary considerably across different populations and ethnicities4,5, making the pooling of data and its interpretation even more difficult. As a result, neurologists commonly lack reliable reference data to be able to offer tailored counseling and treatment to patients with genetic PD and other hereditary neurological diseases.
Targeted treatment options for genetic PD are increasingly being developed, with several gene-specific frontrunners now entering clinical trial6,7. Identifying eligible patients for such trials is imperative and eligibility criteria do not only comprise the genotype, but also demographic and clinical characteristics. The need for reliable data on the one hand and the need to identify and characterize more patients on the other are in fact mutually dependent on one another and can both be addressed with a ‘global neurologist mindset’ where collaboration is key. Since the 1990s, there has been a growing interest and investment in large-scale, team-based research initiatives to address complex and multifaceted problems that require collaboration across different disciplines8. Likewise, there is an increasing necessity for – ideally global-scale - team science approaches of clinicians and researchers with similar interests joining forces to promote advanced research and to improve patient care.
Employing novel ways of team science, electronic databases, and global communication, we performed a worldwide survey of genetic PD with an emphasis on availability of demographic, clinical and biomarker data and materials, to both foster and exploit global collaboration. In order to identify possible participants for our survey, we compiled the names of corresponding authors from articles included in the Movement Disorder Society Genetic mutation database (MDSGene, see Supplement 1 and www.mdsgene.org). Six causes of monogenic PD were included: SNCA, LRRK2, VPS35, Parkin, PINK1, and DJ1. When the project was conceived, GBA had yet to be included in the MDSGene database, so we screened the literature according to MDSGene criteria to identify corresponding authors of eligible articles (articles published in English with clinical information available). In addition, the “Genetic Epidemiology of Parkinson’s disease” consortium (https://geopd.lcsb.uni.lu) contributed members not already identified as a corresponding author of publications represented in MDSGene. Additional contacts were included upon recommendation of participants (see Supplement 2).
We developed an online survey on demographic, clinical, genetic, and additional data (for details, see Supplement 3) and invited the previously identified researchers to report availability of information in their samples of genetic PD patients. To avoid multiple reporting of the same cases, we asked participants to indicate sharing of samples and encouraged participants from the same center to nominate one person to report all cases or to divide up the cases between reporting researchers. The survey was open for contributions for 5 weeks from March until May 2018. Two rounds of email reminders were sent out after two weeks each to enhance the response rate. Participants received no financial compensation for their contribution.
A total of 103 researchers from different centers in 43 countries reported n=8,453 PD patients with mutations in PD genes (Figure 1). The overall response rate to our invitation to participate in this project was 45% (n=162); 79% (n=128) of the respondents completed the survey (see Supplement 2). Of these, 98% (n=125) indicated their interest in further collaboration, and 45% (n=57) of the researchers sent personal emails expressing their interest to contribute further to this project and/or suggesting additional collaborative projects (Figure 2). Reflecting the worldwide distribution of participating centers, the backgrounds of the reported patient samples were diverse and include Arab, Asian, Ashkenazi Jewish, Caucasian, Hispanic, Indian, Mennonites, and North African. Patients were reported to carry mutations in SNCA (n=263), LRRK2 (n=3,182), VPS35 (n=35), Parkin (n=1,530), PINK1 (n=260), DJ1 (n=29), or GBA risk alleles (n=3,154). The total number of reported monogenic PD cases in the present study exceeds published cases by a factor of 2.6 (n=5,299 vs. n=2,064 cases (www.mdsgene.org), both excluding GBA) indicating that the majority of patients with genetic PD are not yet reflected in the published literature. There is, thus, a large number of genetically defined patients readily available but not yet included in specific research projects, let alone clinical trials.
Figure 1.
Worldwide centers reporting patients with monogenic Parkinson disease (PD) and PD patients with variants in GBA . Please find a detailed list of the participating members of the MJFF Global Genetic Parkinson's Disease Study Group in Supplementary Table 1.
Figure 2: Response quantification.
Of the n=336 researchers we contacted, n=125 (98% of those who completed the survey) were interested in further collaboration on genetic PD. Of those researchers who did not respond to our invitation to participate, we identified n=52 (29%) to be affiliated with one of the responding centers. For details, please see eFigure 1.
Regarding data quality and completeness, information on PD nonmotor signs is scarce in the literature, and even for cognition, published information is available only for about a third (660/2064) of the cases with monogenic PD (www.mdsgene.org)4,5. In contrast, our present approach indicates availability of nonmotor signs in general for 67% (3,525/5,299) of the reported cases. Given the increasing difficulty to publish clinical-genetic case reports or series, along with broad(er) access to diagnostic genetic testing, we predict this trend of, first, non-reporting of genetic PD patients and, second, of not publishing data at the individual patient level to quickly grow.
To fill these gaps, a new collaborative mindset is indispensable. By joining forces in a worldwide collaborative effort, our study was able to reveal an unprecedented level of data completeness, a paramount prerequisite when aiming to perform meaningful genotype-phenotype correlations and when selecting patients for clinical studies and trials4,5. In addition to sharing unpublished data, team science of clinicians and researchers in the field of rare neurological diseases will facilitate sharing of expertise, promote new research opportunities, offer a network to foster new training opportunities for young researchers, and finally, advance development of individualized therapies. Based on the enthusiastic responses to our survey and the high willingness to collaborate, we are confident that we have successfully established a team science approach that will specifically enable i) successfully increasing sample sizes of patients with rare neurological diseases; ii) leveraging neurology expertise globally; and iii) fostering team science among neurologists worldwide.
Supplementary Material
Table 1. Availability of information.
The participating centers were asked to report availability of an item if the relating data was available for at least a subset of the reported PD patients registered at their center.
| number of centers reporting available information (percentage of total participating centers (n=103)) |
|
|---|---|
| Age | 102 (99%) |
| Sex | 102 (99%) |
| Ethnicity | 101 (98%) |
| Pedigree | 94 (91%) |
| Age at onset | 97 (94%) |
| Unified Parkinson Disease Rating Scale (UPDRS) | 68 (66%) |
| Hoehn & Yahr Scale | 75 (73%) |
| Dopaminergic medications | 79 (77%) |
| Nonmotor signs | 68 (66%) |
| Environmental exposures | 48 (47%) |
| Life style variables | 36 (35%) |
| Treatment response | 76 (74%) |
| Omics data | 17 (17%) |
| -Genomics | 14 (14%) |
| -Transcriptomics | 2 (2%) |
| -Proteomics | 1 (1%) |
| -Metabolomics | 1 (1%) |
| Imaging | 38 (37%) |
| -MRI | 33 (32%) |
| -SPECT/PET | 19 (18%) |
| -TCS | 7 (7%) |
| DNA | 88 (85%) |
| RNA | 22 (21%) |
| Serum | 28 (27%) |
| Plasma | 26 (25%) |
| Whole blood | 23 (22%) |
| Cerebrospinal fluid | 8 (8%) |
| Fibroblasts | 12 (12%) |
| iPSCs | 11 (11%) |
| Brain tissue | 11 (11%) |
Acknowledgments
Michael J. Fox Foundation: EJV, HM, CK
German Research Foundation FOR2488: NB, KL, MK, CK
Appendix
MJFF Global Genetic Parkinson’s Disease Study Group
| Name | Title | Affiliations |
|---|---|---|
| Eva-Juliane Vollstedt | MD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany |
| Norbert Brüggemann | MD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany; Department of Neurology, University of Luebeck, Luebeck, Germany |
| Katja Lohmann | PhD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany |
| Harutyun Madoev | MSc | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany |
| Shalini Padmanabhan | PhD | Research Programs, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA |
| Anna Naito | PhD | Research Programs, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA; Research Programs, Parkinson’s Foundation, Miami, Florida, USA |
| Sonja Petkovic | PhD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany |
| Jan Aasly | MD | Department of Neurology, St. Olavs Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway |
| Charles Adler | MD, PhD | Department of Neurology, Mayo Clinic College of Medicine, Scottdale, Arizona, USA |
| Azlina Ahmad-Annuar | PhD | Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia |
| Alberto Albanese | MD | Department of Neurology, IRCCS Istituto Clinico Humanitas, Rozzano, Milano, Italy; Department of Neurology, Catholic University, Milano, Italy |
| Roy Alcalay | MD, MS | Department of Neurology, Columbia University, New York, New York, USA |
| Bashayer Al-Mubarak | PhD | Behavioural genetics Unit, Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia |
| Victoria Alvarez | PhD | Laboratório de Genética, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain |
| Brennie Andree-Muñoz | MD | Department of Neurology, Hospital Luis Vernaza, Guayaquil, Equador |
| Grazia Annesi | PhD | Institute of Molecular Bioimaging and Physiology, National Research Council, Germaneto, Cantazaro, Italy |
| Silke Appel-Cresswell | MD | Pacific Parkinson’s Research Centre, Division of Neurology, Department of Medicine, Vancouver, British Columbia, Canada |
| David Arkadir | MD, PhD | Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel |
| Sebastian Armasu | MSc | Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA |
| Thomas R. Barber | MD | Oxford Parkinson’s Disease Centre, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, Oxfordshire, United Kingdom |
| Soraya Bardien | MD | Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa |
| Melinda Barkhuizen | PhD | DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, North-West, South Africa |
| Matthew J. Barrett | MD | Department of Neurology, University of Virginia, Charlottesville, Virginia, USA |
| A. Nazli Başak | PhD | Department of Molecular Biology and Genetics, Koç University School of Medicine, KUTTAM, Suna and Inan Kiraç Foundation, NDAL, Istanbul, Turkey |
| Thomas Beach MD | MD, PhD | Civin Laboratory of Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, USA |
| Bruno A. Benitez | MD | Department of Psychiatry, Washington University in Saint Louis, Saint Louis, Missouri, USA |
| Daniela Berg | MD | Department of Neurology, Christian-Albrechts-Universität, Kiel, Germany |
| Kailash Bhatia | MD | Clinical Movement Disorders, UCL Institute of Neurology, University College London, London, United Kingdom; Clinical Neurology, National Hospital for Neurology, University College London, London, United Kingdom |
| Ferdinand Binkofski | MD | Clinical Cognitive Research, Department of Neurology, University Hospital RWTH Aachen, Aachen, Germany; Institute for Neuroscience and Medicine (INM-4), Research Center Juelich, Juelich, Germany |
| Cornelis Blauwendraat | PhD | Laboratory of Neurogenetics, National Institute on Ageing, National Institutes of Health, Bethesda, Maryland, USA |
| Vincenzo Bonifati | MD, PhD | Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands |
| Vanderci Borges | MD | Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil |
| Maria Bozi | MD, PhD | Parkinson's and Movement Disorders Unit, Attiko Hospital, University of Athens, Haidari, Athens, Greece; Department of Neurology, Athens Psychiatry Hospital, NHS, Haidari, Athens, Greece |
| Alexis Brice | MD | ICM, Institut du Cerveau et de la Moelle épinière, Paris, France; UMR 1127, NS-PARK/FCRIN, Inserm, Paris, France; Sorbonne Université, Paris, France; UMR 7225, CNRS, Paris, France; Department of Genetics, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France |
| Laura Brighina | MD, PhD | Department of Neurology, Milan Center for Neuroscience, University of Milano-Bicocca/San Gerardo Hospital, Monza, Monza Brianza, Italy |
| Kathrin Brockmann | MD | Department of Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Baden Wuerttemberg, Germany; Hertie Institute for Clinical Brain Research and German Centre for Neurodegenerative Diseases, Tuebingen, Baden Wuerttemberg, Germany |
| Marta Camacho | MSc | Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom |
| Francisco Cardoso | MD, PhD | Department of Internal Medicine, UFMG, Belo Horizonte, Minas Gerais, Brazil |
| Andrea Carmine Belin | PhD | Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden |
| Jonathan Carr | MD | Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa |
| Piu Chan | MD, PhD | Department of Neurobiology and Neurology, Capital Medical University, Xuanwu Hospital, Beijing, Beijing, China |
| Jorge Chang-Castello | MD | Department of Molecular Biology, Hospital Luis Vernaza, Guayaquil, Ecuador |
| Bruce Chase | PhD | Department of Biology, University of Nebraska at Omaha, Omaha, Nebraska, USA |
| Alice Chen-Plotkin | MD | Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA |
| Sun Ju Chung | MD, PhD | Medical Genetic Center, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea |
| Roberto Cilia | MD | ASST Pini-CTO, Parkinson Institute, Milan, Milan, Italy |
| Jordi Clarimon | PhD | Department of Neurology, Biomedical Research Institute IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain |
| Lorraine Clark | PhD | Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, New York, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, New York, USA; Laboratory of Personalized Genomic Medicine, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New York, New York, USA |
| Mario Cornejo-Olivas | MD | Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru |
| Jean-Christophe Corvol | MD | ICM, Institut du Cerveau et de la Moelle épinière, Paris, France; UMR 1127, NS-PARK/FCRIN, Inserm, Paris, France; Sorbonne Université, Paris, France; UMR 7225, CNRS, Paris, France; Department of Genetics, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France |
| Carlos Cosentino | MD | Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru |
| Patrick Cras | MD, PhD | Department of Neurology, Antwerp University Hospital, Edegem, Belgium; Born Bunge Institute, Department of Neurology, University of Antwerp, Wilrijk, Belgium |
| David Crosiers | MD, PhD | Department of Neurology, Antwerp University Hospital, Edegem, Belgium; Born Bunge Institute, Department of Neurology, University of Antwerp, Wilrijk, Belgium; Center for Molecular Neurology, VIB, Wilrijk, Belgium |
| Joana Damásio | MD | Department of Neurology, Hospital de Santo António - Centro Hospitalar do Porto, Porto, Portugal |
| Parimal Das | PhD | Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India |
| Patricia de Carvalho Aguiar | MD, PhD | Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil; Instituto Israelita de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo, Brazil |
| Giuseppe De Michele | MD | Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy |
| Anna De Rosa | MD, PhD | Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy |
| Elena Dieguez | MD | Neurology Institute, Universidad de la Republica, Montevideo, Uruguay |
| Jolanta Dorszewska | MD, PhD | Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland |
| Sevda Erer | MD | Department of Neurology, Uludag University, Neurology, Bursa, Turkey |
| Sibel Ertan | MD | Department of Neurology, Istanbul University, Cerrahpaşa School of Medicine, Istanbul, Turkey |
| Ekaterina Fedotova | MD, PhD | Department of Neurogenetics, Research Center of Neurology, Moscow, Russia |
| Rosangela Ferese | PhD | IRCCS Neuromed, Localita’ Camerelle, Pozzilli, Isernia, Italy |
| Carlo Ferrarese | MD | Department of Neurology, Milan Center for Neuroscience, University of Milano-Bicocca/San Gerardo Hospital, Monza, Monza Brianza, Italy |
| Henrique Ferraz | MD | Department of Neurology, Universidade Federal de São Paulo, São Paulo, Brazil |
| Ondrej Fiala | MD, PhD | Department of Neurology, Institute of Neuropsychiatric Care (INEP), Prague, Czech Republic |
| Tatiana Foroud | PhD | Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA |
| Andrzej Friedman | MD, PhD | Department of Neurology, Medical University in Warsaw, Warsaw, Poland |
| Roberta Frigerio | MD | Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA |
| Manabu Funayama | PhD | Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo, Tokyo, Japan |
| Stefano Gambardella | PhD | IRCCS Neuromed, Localita’ Camerelle, Pozzilli, Isernia, Italy |
| Gaetan Garraux | MD, PhD | Department of Neurology, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium; MoVeRe group, GIGA-CRC in vivo imaging, University of Liege, Liège, Belgium |
| Emilia M. Gatto | MD | Movement Disorders, Department of Neurology, Instituto de Neurosciencias Buenos Aires, Buenos Aires, Argentina |
| Gençer Genç | MD | Department of Neurology, Şişli Etfal Training and Research Hospital, Istanbul, Turkey |
| Stefano Goldwurm | MD, PhD | ASST Pini-CTO, Parkinson Institute, Milan, Milan, Italy; Department of Neuroscience "Rita Levi Montalcini", University of Turin, Turin, Italy |
| Juan Carlos Gomez-Esteban | PhD, MD | Neurodegenerative diseases, Biocruces Research Institute, Biocruces, Barakaldo, Bizkaia, Spain |
| Pilar Gómez-Garre | PhD | Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Instituto de Biomedicina de Sevilla, Seville, Seville, Spain |
| Ana Gorostidi | PhD | Genomics Platform, Biodonostia Research Institute, San Sebastian, Gipuzkoa, Spain; Neuroscience Area, Biodonostia Research Institute, San Sebastian, Gipuzkoa, Spain |
| Donald Grosset | MD | Institute of Neurological Sciences, NHS Greater Glasgow & Clyde, Queen Elizabeth University Hospital, Glasgow, Scotland, United Kingdom; Institute of Neuroscience & Psychology, University of Glasgow, Glasgow, Scotland, United Kingdom |
| Hasmet Hanagasi | MD | Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey |
| John Hardy | MD | Neurodegenerative Disease, University College London, UCL Institute of Neurology, London, United Kingdom |
| Anhar Hassan | MD | Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA |
| Nobutaka Hattori | MD, PhD | Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan |
| Robert A. Hauser | MD | Parkinson's Disease and Movement Disorders Center, Department of Neurology, University of South Florida, Tampa, Florida, USA |
| Peter Hedera | MD, PhD | Division of Movement Disorders, Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA |
| Faycal Hentati | MD | Mongi Ben Hamida National Institute of Neurology, Tunis, Tunisia |
| Jens Michael Hertz | MD | Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark |
| Janice L. Holton | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom |
| Henry Houlden | MD | Neuromuscular Diseases, UCL Institute of Neurology, University College London, London, United Kingdom |
| Mara H. Hutz | PhD | Departamento de Genética, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil |
| Takeshi Ikeuchi | MD, PhD | Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Niigata, Japan |
| Sergey Illarioshkin | MD, PhD | Department of Neurogenetics, Research Center of Neurology, Moscow, Russia |
| Miguel Inca-Martinez | BS | Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru |
| Jon Infante | MD, PhD | Department of Neurology, University Hospital Marques de Valdecilla, IDIVAL, University of Cantabria, Santander, Cantabria, Spain |
| Joseph Jankovic | MD | Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA |
| Beom Seok Jeon | MD, PhD | Department of Neurology, Seoul National University Hospital, Seoul, South Korea |
| Silvia Jesús | MD, PhD | Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Instituto de Biomedicina de Sevilla, Seville, Seville, Spain |
| Marlene Jimenez-Del-Rio | MSc, DSc | Department of Neurosciences, Universidad de Antioquia, Medellin, Colombia |
| Hiroshi Kataoka | MD | Department of Neurology, Nara Medical University, Kashihara, Nara, Japan |
| Hideshi Kawakami | MD, PhD | Epidemiology, Research Institute for Radiation Biology & Medicine, Hiroshima University, Hiroshima, Hiroshima, Japan |
| Yun Joong Kim | MD, PhD | ILSONG Institute of Life Science, Hallym University, Anyang-si, Gyeonggi-do, South Korea; Department of Neurology, Hallym University, Anyang-si, Gyeonggi-do, South Korea |
| Péter Klivényi | MD | Department of Neurology, University of Szeged, Szeged, Hungary |
| Sulev Koks | MD, PhD | The Perron Institute for Neurological and Translational Science, Nedlands, Western Australia, Australia |
| Vladimir Kostić | MD | Department for Neurodegeneration, Clinic for Neurology CCS, Belgrade, Serbia |
| Dariusz Koziorowski | MD, PhD | Department of Neurology, Medical University in Warsaw, Warsaw, Poland |
| Anna Krygowska-Wajs | MD | Department of Neurology, Collegium Medicum, Jagiellonian University, Krakow, Poland |
| Jaime Kulisevsky | MD, PhD | Department of Neurology, Biomedical Research Institute IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain |
| Anthony Lang | MD | Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada |
| Mark LeDoux | MD, PhD | Department of Psychology and School of Health Studies, University of Memphis, Memphis, |
| Suzanne Lesage | MD | ICM, Institut du Cerveau et de la Moelle épinière, Paris, France; UMR 1127, NS-PARK/FCRIN, Inserm, Paris, France; Sorbonne Université, Paris, France; UMR 7225, CNRS, Paris, France; Department of Genetics, Hôpital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France |
| Shen-Yang Lim | MD | Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson’s & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia |
| Chin-Hsien Lin | MD, PhD | Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan |
| Francisco Lopera | MD | Department of Neurosciences, Universidad de Antioquia, Medellin, Colombia |
| Grisel Lopez | MD | Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA |
| Chin-Song Lu | MD | Professor Lu Neurological Clinic, Taoyuan, Taiwan |
| Tim Lynch | MD | Department of Neurology, The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland |
| Maciej Machaczka | MD | Department of Clinical Science and Education, Stockholm South Hospital and Karolinska Institutet, Stockholm, Sweden; Medical Faculty, University of Rzeszow, Rzeszow, Poland |
| Marina Magalhães | MD | Department of Neurology, Hospital de Santo António - Centro Hospitalar do Porto, Porto, Portugal |
| Kari Majamaa | MD | Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland; Department of Neurology, Medical Research Center, Oulu University Hospital, Oulu, Finland |
| Demetrius Maraganore | MD | Department of Neurology, Northshore University Health System, Glenview, Illinois, USA |
| Karen Marder | MD | Department of Neurology, Columbia University, New York, New York, USA |
| Katerina Markopoulou | MD, PhD | Department of Neurology, Northshore University Health System, Glenview, Illinois, USA; Department of Neurology, University of Chicago, Chicago, Illinois, USA |
| Mika Henrik Martikainen | MD, PhD | Department of Neurology, Faculty of Medicine, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Department of Neurology, Turku University Hospital, Turku, Finland |
| Ignacio Mata | PhD | Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Neurology, University of Washington, Seattle, Washington, USA |
| Pilar Mazzetti | MD | Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru |
| George Mellick | MD | Griffith Institute for Drug Discovery (GRIDD), School of Environment and Science, Griffith University, Brisbane, Queensland, Australia |
| Manuel Menéndez-González | MD | Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain |
| Federico Micheli | MD | Movement Disorders, Hospital de Clínicas José de San Martin, Buenos Aires, Argentina |
| Anat Mirelman | PhD | Movement Disorders, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel |
| Pablo Mir | MD, PhD | Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain; Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Instituto de Biomedicina de Sevilla, Seville, Seville, Spain |
| Hiroyuki Morino | MD, PhD | Epidemiology, Research Institute for Radiation Biology & Medicine, Hiroshima University, Hiroshima, Hiroshima, Japan |
| Huw Morris | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom |
| Renato P. Munhoz | MD, PhD | Parana Parkinson's Association, Curitiba, Paraná, Brazil; Movement Disorders Centre, Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada |
| Diana Angelika Olszewska | MD, PhD | Department of Neurology, The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland |
| Laurie J. Ozelius | PhD | Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA |
| Coro Paisán-Ruiz | PhD | Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Mindich Child Health and Development, Icahn School of Medicine at Mount Sinai, New York, New York, USA |
| Haydeh Payami | MD | Departments of Neurology and Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA |
| Silvio Peluso | MD, PhD | Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy |
| Simona Petrucci | MD, PhD | Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Division of Medical Genetics, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy |
| Gianni Pezzoli | MD | ASST Pini-CTO, Parkinson Institute, Milan, Milan, Italy |
| Márcia Pimentel | PhD | Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil |
| Walter Pirker | MD | Department of Neurology, Wilhelminenspital, Vienna, Austria |
| Peter P. Pramstaller | MD | Institute for Biomedicine, Affiliated Institute of the University of Lübeck, Eurac Research, Bolzano, South Tyrol, Italy; Department of Neurology, Central Hospital, Bolzano, South Tyrol, Italy |
| Teeratorn Pulkes | MD | Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Rajthevi, Bangkok, Thailand |
| Andreas Puschmann | MD, PhD | Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden; Department of Neurology, Skåne University, Lund, Sweden |
| Aldo Quattrone | MD | Institute of Molecular Bioimaging and Physiology, National Research Council, Germaneto, Cantazaro, Italy |
| Victor Raggio | MD | Department of Genetics, Universidad de la Republica, Montevideo, Uruguay |
| Gerhard Ransmayr | MD | Department of Neurology 2, Kepler University Hospital, Linz, Austria |
| Carlos Rieder | MD | Movement Disorders Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil |
| Olaf Riess | MD | Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany |
| Federico Rodriguez-Porcel | MD | Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA |
| Ekaterina Rogaeva | PhD | Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada |
| Owen A. Ross | MD | Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA |
| Javier Ruiz-Martinez | MD, PhD | Neuroscience Area, Biodonostia Research Institute, San Sebastian, Gipuzkoa, Spain; Department of Neurology, University Hospital Donostia, San Sebastian, Gipuzkoa, Spain |
| Esther Sammler | MD, PhD | Neurology Department, Ninewells Hospital and Medical School, Dundee, United Kingdom; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom |
| Marta San Luciano | MD, MS | Department of Neurology, Movement Disorders and Neuromodulation Center, University of California San Francisco, San Francisco, California, USA |
| Wataru Satake | MD, PhD | Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan |
| Rachel Saunders-Pullman | MD | Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA |
| Ali Sazci | PhD | Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli, Kocaeli, Turkey |
| Clemens Scherzer | MD | Center for Advanced Parkinson's Disease Research, Department of Neurology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA |
| Anette Schrag | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom |
| Artur Schumacher-Schuh | MD, PhD | Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil |
| Manu Sharma | PhD | Institute for Clinical Epidemiology and Applied Biometry, Centre for Genetic Epidemiology, University of Tuebingen, Tuebingen, Germany |
| Ellen Sidransky | MD | Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA |
| Andrew B. Singleton | PhD | Laboratory of Neurogenetics, National Institute on Ageing, National Institutes of Health, Bethesda, Maryland, USA |
| Maria Skaalum Petersen | PhD | Department of Occupational Medicine and Public Health, The Faroese Hospital System, Tórshavn, Faroe Islands; Faculty of Health Sciences, Centre of Health Science, University of the Faroe Islands, Tórshavn, Faroe Islands |
| Stefanie Smolders | Born Bunge Institute, Department of Neurology, University of Antwerp, Wilrijk, Belgium; Center for Molecular Neurology, VIB, Wilrijk, Belgium; Biomedical Sciences, University of Antwerp, Wilrijk, Belgium |
|
| Mariana Spitz | MD, PhD | Department of Neurology, State University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil |
| Leonidas Stefanis | MD | First Department of Neurology, Medical School of the National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece; Translational Medicine, Biomedical Research Foundation of the Academy of Athens, Athens, Greece |
| Walter Struhal | MD | Department for Neurology, Karl Landsteiner Private University, Tulln, Lower Austria, Austria |
| Carolyn Sue | MD | Department of Neurogenetics, Kolling Institute, University of Sydney, Sydney, New South Wales, Australia; Department of Neurology, Royal North Shore Hospital, St Leonards, New South Wales, Australia |
| Matthew Swan | MD | Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA |
| Maria Swanberg | PhD | Translational Neurogenetics Unit, Wallenberg Neuroscience Center, BMC A10, Experimental Medical Science, Lund University, Lund, Sweden |
| Pille Taba | MD, PhD | Department of Neurology and Neurosurgery, University of Tartu, Tartu, Estonia |
| Ricardo Taipa | MD, PhD | Portuguese Brain Bank, Neuropathology Unit, Department of Neurosciences, Centro Hospitalar Universitário do Porto, Porto, Portugal |
| Manuela Tan | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom |
| Ai Huey Tan | MD | Division of Neurology and the Mah Pooi Soo & Tan Chin Nam Centre for Parkinson’s & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia |
| Eng-King Tan | MD | Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore General Hospital, Singapore, Singapore |
| Beisha Tang | MD | Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; Department of Gerontology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; National Clinical Research Center for Geritatric Disorders (Xiangya), Changsha, Hunan Province, China; Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan Province, China |
| Nahid Tayebi | PhD | Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA |
| Avner Thaler | MD, PhD | Movement Disorders, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel |
| Astrid Thomas | MD, PhD | Department of Neuroscience Imaging and clinical sciences, Institute of Neurology, University Chieti Pescara, Chieti, Italy |
| Tatsushi Toda | MD, PhD | Department of Neurology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan |
| Mathias Toft | MD, PhD | Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway |
| Luis Torres | MD | Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru |
| Vitor Tumas | MD | Movement Disorders Unit, Universidade de São Paulo, Ribeirão Preto, Brazil |
| Enza Maria Valente | MD, PhD | Neurogenetics Unit, IRCCS Fondazione Santa Lucia, Rome, Italy; Division of Medical Genetics, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy |
| Christine Van Broeckhoven | MD | Born Bunge Institute, Department of Neurology, University of Antwerp, Wilrijk, Belgium; Center for Molecular Neurology, VIB, Wilrijk, Belgium; Biomedical Sciences, University of Antwerp, Wilrijk, Belgium |
| Laszlo Vecsei | MD | Department of Neurology, University of Szeged, Szeged, Hungary; Neuroscience Research Group, MTA-SZTE, Szeged, Hungary |
| Carlos Velez-Pardo | MSc, DSc | Department of Neurosciences, Universidad de Antioquia, Medellin, Colombia |
| Marie Vidailhet | MD | ICM, Institut du Cerveau et de la Moelle épinière, Paris, France; Sorbonne Université, Paris, France; Department of Neurology, Hôpital Pitié-Salpêtrière, Paris, France |
| Thomas T. Warner | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom; Reta Lila Weston Institute, UCL Institute of Neurology, University College London, London, United Kingdom |
| Caroline H. Williams-Gray | MRCP, PhD | Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom |
| Juliane Winkelmann | MD | Institute of Neurogenomics, Helmholtz Zentrum Muenchen, Neuherberg, Germany; Neurogenetics, Technische Universitaet Muenchen, Munich, Germany; Institute of Human Genetics, Klinikum rechts der Isar der TUM, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany |
| Dirk Woitalla | MD | Department of Neurology, St.Josef Krankenhaus, Essen, Germany; Department of Neurology, Ruhr-Universitaet Bochum, Bochum, Germany |
| Nicholas W. Wood | MD | Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom |
| Zbigniew K. Wszolek | MD | Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA |
| Ruey-Meei Wu | MD | Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan |
| Yih-Ru Wu | MD | Department of Neurology, Chang Gung University, Chang Gung Memorial Hospital, Taipei, Taiwan |
| Tao Xie | MD, PhD | Department of Neurology, University of Chicago, Chicago, Illinois, USA |
| Hiroyo Yoshino | PhD | Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo, Tokyo, Japan |
| Baorong Zhang | MD | Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China |
| Alexander Zimprich | MD | Department of Neurology, Medical University, Vienna, Austria |
| Rejko Krüger | MD | University of Luxembourg, Esch-sur-Alzette, Luxembourg |
| Matthew Farrer | PhD | Centre for Applied Neurosciences, University of British Columbia, Vancouver, British Columbia, Canada |
| Inke R. König | PhD | Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck, Germany |
| Meike Kasten | MD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany |
| Christine Klein | MD | Institute of Neurogenetics, University of Luebeck, Luebeck, Germany |
References
- 1.Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007;68(5):384–386. doi: 10.1212/01.wnl.0000247740.47667.03. [DOI] [PubMed] [Google Scholar]
- 2.Domingo A, Klein C. Genetics of Parkinson disease. Handb Clin Neurol. 2018;147:211–227. doi: 10.1016/B978-0-444-63233-3.00014-2. [DOI] [PubMed] [Google Scholar]
- 3.Anheim M, Elbaz A, Lesage S, et al. Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers. Neurology. 2012;78(6):417–420. doi: 10.1212/WNL.0b013e318245f476. [DOI] [PubMed] [Google Scholar]
- 4.Kasten M, Hartmann C, Hampf J, et al. Genotype-Phenotype Relations for the Parkinson’s Disease Genes Parkin , PINK1 , DJ1: MDSGene Systematic Review. Mov Disord. 2018;33(5):730–741. doi: 10.1002/mds.27352. [DOI] [PubMed] [Google Scholar]
- 5.Trinh J, Zeldenrust FMJ, Huang J, et al. Genotype-phenotype relations for the Parkinson’s disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Mov Disord. October 2018. doi: 10.1002/mds.27527. [DOI] [PubMed] [Google Scholar]
- 6.A Global Study to Assess the Drug Dynamics, Efficacy, and Safety of GZ/SAR402671 in Parkinson’s Disease Patients Carrying a Glucocerebrosidase (GBA) Gene Mutation (MOVES-PD). https://clinicaltrials.gov/ct2/show/NCT02906020. [Google Scholar]
- 7.Olanow CW, Kordower JH. Targeting α-Synuclein as a therapy for Parkinson’s disease: The battle begins. Mov Disord. 2017;32(2):203–207. doi: 10.1002/mds.26935. [DOI] [PubMed] [Google Scholar]
- 8.Stokols D, Hall KL, Taylor BK, Moser RP. The Science of Team Science. Am J Prev Med. 2008;35(2):S77–S89. doi: 10.1016/j.amepre.2008.05.002. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.