Embracing monogenic Parkinson's disease: the MJFF global genetic PD cohort

RESEARCH ARTICLE Embracing Monogenic Parkinson’s Disease: The MJFF Global Genetic PD Cohort Eva-Juliane Vollstedt, MD, 1 Susen Schaake, BSc, 1 Katja Lohmann, PhD, 1 Shalini Padmanabhan, PhD, 2 Alexis Brice, MD, 3 Suzanne Lesage, PhD, 4 Christelle Tesson, PhD, 4 Marie Vidailhet, MD, 3 Isabel Wurster, MD, 5 Faycel Hentati, MD, 6 Anat Mirelman, PhD, 7 Nir Giladi, MD, 8 Karen Marder, MD, MPH, 9 Cheryl Waters, MD, 10 Stanley Fahn, MD, 10 Meike Kasten, MD, 11 Norbert Brüggemann, MD, 12 Max Borsche, MD, 12 Tatiana Foroud, PhD, 13 Eduardo Tolosa, MD, PhD, 14 Alicia Garrido, MD, 14 Grazia Annesi, PhD, 15 Monica Gagliardi, PhD, 15 Maria Bozi, MD, PhD, 16 Leonidas Stefanis, MD, PhD, 17 Joaquim J. Ferreira, MD, PhD, 18 Leonor Correia Guedes, MD, PhD, 19 Micol Avenali, MD, 20 Simona Petrucci, MD, PhD, 21 Lorraine Clark, PhD, 22 Ekaterina Y. Fedotova, MD, 23 Natalya Y. Abramycheva, PhD, 23 Victoria Alvarez, MD, PhD, 24 --------------------------------------------------------- This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. *Correspondence to: Dr. Christine Klein, Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee, 160 23538 Lübeck, Germany; E-mail: [email protected]luebeck.de Members of the MJFF Global Genetic Parkinson’s Disease Study Group are listed in the Appendix. Relevant conflicts of interest/financial disclosures: Alexis Brice: France Parkinson +FRC Grant (toward the identification of novel recessive genes in Parkinson’s disease using homozygosity mapping, exome sequencing, and functional analysis in zebrafish), Grant ANREPIG—Agence nationale de recherche (DEcipher the ComplexIty and Plasticity of epigenomic cHaracteristics under influence of Environmental factors in the pathomechanistic Regulation of Parkinson’sDisease [DecipherPD]), Grant ANR-JPND—Agence nationale de recherche (Courage PD), Institut de France (Prize Allianz 2018); Faycel Hentati: Glaxo 2000–2001: Genetic epidemiological studies of Parkinson’s disease in Tunisia study 1993–2001 study, Genetic GlaxoSmithKline project epidemiological in Tunisia (2002–2002-2004), MJF 2008: Clinicogenetic studies of LRRK2 G2019S in Tunisia MJF 2008, Lundbeck A/S Denmark 2017: An epidemiological and longitudinal study of family members of Parkinson patients carrying LRRK2 gene mutations; Nir Giladi: receives support from the Sieratzki Family Foundation and the Aufzien Academic Center in Tel-Aviv University; Karen Marder: The Michael J. Fox Foundation, Parkinson’sDisease Foundation, NIH NS036630, UL1TR000040; Tatiana Foroud: MJFF, NIH/NINDS; Eduardo Tolosa: Spanish Network for Research on Neurodegenerative Disorders (CIBERNED)- Instituto Carlos III (ISCIII), and The Michael J. Fox Foundation for Parkinson’s Research (MJFF); Lorraine Clark: NIH R21 NS05847 (Clark) Glucocerebrosidase mutations and Parkinson’s disease in the Ashkenazim (07/01/05–06/30/07), NIH 2P50 AG008702-21 (Shelanski) Project 3 (Clark) Glucocerebrosidase mutations and dementia with Lewy bodies (06/01/10–05/31/15), NIH R01 NS060113 (Clark) Molecular genetic analysis of lysosomal storage disorder genes in Parkinson’s disease (09/29/08–08/31/12), NIH R03 NS113038 (Clark) Development of a GBA p.E326K associated Parkinson’s disease and dementia with Lewy body mouse model (07/31/19–06/30/21); Victoria Alvarez: Spanish Fondo de Investigaciones Sanitarias grants (grant number FIS-FEDER PI15/00878); Manuel Menéndez-Gonz alez: Instituto de Salud Carlos III; Andrea Carmine Belin: Karolinska Institutet Research Funds, the Swedish Parkinson Foundation; Jordi Clarimon: full-time employee at Lundbeck A/S (Denmark); Caroline H. Williams-Gray: This work was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care; Yih-Ru Wu: Minister of Science and Technology, Taiwan (NSC 95-2314-B-182A-061, NSC 98-2628-B-182A-001-MY3, NSC102-2314-B-182A-113-MY2), Chang Gung Memorial Hospital, Taipei, Taiwan (CMRPG3H0311–3; CMRPG3K1481); George D. Mellick: Australian NHMRC APP1084560, Identification of Parkinson’s disease genes in Queensland families showing patterns of Mendelian inheritance; Jolanta Dorszewska: Grant for independent researchers (Ministry of Science and Higher Education, Poland 10/KG/2018), no. 502-01-11111677-05851, Grant of Poznan University of Medical Sciences, no. 502-14-01111677-10342, The Michael J. Fox Foundation for Parkinson’s Research, USA through Prof. Christine Klein, University of Lübeck, Germany; Wataru Satake: AMED (grant numbers 17ek0109207h0001 and 22kk030517h0001 to Wataru SATAKE) and JSPS (under grant numbers 21H02836 and 17H04056 to Wataru SATAKE); Shen-Yang Lim: Grants from The Michael J. Fox Foundation; Melinda Barkhuizen: Genetic research funding: National Research Foundation South Africa (doctoral grant), DST/NWU Preclinical Drug Development Platform internal funding, sample collection sponsored by Ampath Laboratories in South Africa; Rachel Saunders- Pullman: NIH 1U01NS107016-01A1, 5U01NS094148-04, Bigglesworth Family Foundation; Mathias Toft: Regional Health Authority South- Eastern Norway; Silke Appel-Cresswell: Pacific Parkinson’sResearch Institute; Matej Skorvanek: This work was supported by the Operational Programme Integrated Infrastructure, and MS was funded by the ERDF [ITMS2014+:313011V455]; Rejko Krüger: The work of RK is supported by the Fonds National de Recherche (FNR) within the following projects: National Centre for Excellence in Research on Parkinson’s disease (NCER-PD), MotaSYN (12719684), MAMaSyn, MiRisk (C17/BM/11676395) and i2TRON DTU. Moreover, RK is supported by The Michael J. Fox Foundation, and the European Union’s Horizon2020 research and innovation program (Orchestra). RK serves as an editorial board member of the European Journal of Clinical Investigation,theJournal of Parkinsonism and Related Disorders and the Journal of Neural Transmission. RK has received research grants from Fonds National de Recherche de Luxembourg (FNR) as coordinator of the National Centre for Excellence in Research on Parkinson’s disease (NCER-PD), coordinator of the study on COVID-19 National survey for assessing VIral spread by Non-affected CarriErs (CON-VINCE). RK received speaker’s honoraria and/or travel grants from Abbvie, Zambon, and Medtronic, and he participated as PI or site-PI for industry-sponsored clinical trials without receiving honoraria; Eng-King Tan: National Medical Research Council (STaR and PD LCG 0002); Péter Klivényi: Hungarian Brain Research Program (2017–1.2.1-NKP-2017-00002 NAP VI/4), no conflict of interest; Maria Skaalum Petersen: Funding obtained from the Faroese Health Assurance Foundation and the Faroese Parkinson Association; Ruey-Meei Wu: Ministry of Science and Technology, Taiwan (R.O.C.); National Taiwan University Hospital, National Taiwan University; Roy N. Alcalay: RNA is funded by the NIH, DoD, the Parkinson’s Foundation, and The Michael. J. Fox Foundation; Kathrin Brockmann: The Michael J. Fox Foundation; Christine Klein: Grant by The Michael J. Fox Foundation; all other authors report no specific funding and no conflict of Interest concerning the research related to the manuscript. Funding agency: This project was funded by The Michael J. Fox Foundation (ID 15015.02). Received: 22 April 2022; Revised: 20 July 2022; Accepted: 27 July 2022 Published online 24 January 2023 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.29288 286 Movement Disorders, Vol. 38, No. 2, 2023 Manuel Menéndez-Gonz alez, MD, PhD, 25 Silvia Jesús Maestre, MD, PhD, 26 Pilar G omez-Garre, PhD, 26 Pablo Mir, MD, PhD, 26 Andrea Carmine Belin, PhD, 27 Caroline Ran, PhD, 27 Chin-Hsien Lin, MD, PhD, 28 Ming-Che Kuo, MD, 28 David Crosiers, MD, PhD, 29 Zbigniew K. Wszolek, MD, 30 Owen A. Ross, PhD, 31 Joseph Jankovic, MD, 32 Kenya Nishioka, MD, PhD, 33 Manabu Funayama, PhD, 34 Jordi Clarimon, PhD, 35 Caroline H. Williams-Gray, BMBCh, MRCP, PhD, 36 Marta Camacho, MSc, 36 Mario Cornejo-Olivas, MD, 37 Luis Torres-Ramirez, MD, 38 Yih-Ru Wu, MD, 39 Guey-Jen Lee-Chen, PhD, 40 Ana Morgadinho, MD, 41 Teeratorn Pulkes, MD, FRCP, PhD, 42 Pichet Termsarasab, MD, 42 Daniela Berg, MD, 43 Gregor Kuhlenbäumer, MD, 43 Andrea A. Kühn, MD, 44 Friederike Borngräber, MD, 44 Giuseppe de Michele, MD, 45 Anna De Rosa, MD, 45 Alexander Zimprich, MD, 46 Andreas Puschmann, MD, PhD, 47 George D. Mellick, MD, 48 Jolanta Dorszewska, MD, PhD, 49 Jonathan Carr, MD, 50 Rosangela Ferese, PhD, 51 Stefano Gambardella, PhD, 51 Bruce Chase, PhD, 52 Katerina Markopoulou, MD, PhD, 53 Wataru Satake, MD, PhD, 54 Tatsushi Toda, MD, PhD, 55 Malco Rossi, MD, PhD, 54 Marcelo Merello, MD, PhD, 56 Timothy Lynch, FRCPI, FRCP, 57 Diana A. Olszewska, MD, PhD, 57 Shen-Yang Lim, MD, FRACP, 58 Azlina Ahmad-Annuar, PhD, 59 Ai Huey Tan, MD, PhD, FRCP, 58 Bashayer Al-Mubarak, PhD, 60 Hasmet Hanagasi, MD, 61 Dariusz Koziorowski, MD, PhD, 62 Sibel Ertan, MD, 63 Gençer Genç, MD, 64 Patricia de Carvalho Aguiar, MD, PhD, 65 Melinda Barkhuizen, PhD, 66 Marcia M.G. Pimentel, PhD, 67 Rachel Saunders-Pullman, MD, 68 Bart van de Warrenburg, MD, PhD, 69 Susan Bressman, MD, 70 Mathias Toft, MD, PhD, 71 Silke Appel-Cresswell, MD, 72 Anthony E. Lang, MD, 73 Matej Skorvanek, MD, PhD, 74 Agnita J.W. Boon, MD, PhD, 75 Rejko Krüger, MD, 76 Esther M. Sammler, MD, PhD, 77 Vitor Tumas, MD, 78 Bao-rong Zhang, MD, 79 Gaetan Garraux, MD, PhD, 80 Sun Ju Chung, MD, PhD, 81 Yun Joong Kim, MD, PhD, 82 Juliane Winkelmann, MD, 83 Carolyn M. Sue, MD, 84 Eng-King Tan, MD, 85 Joana Dam asio, MD, 86 Péter Klivényi, MD, 87 Vladimir S. Kostic, MD, 88 David Arkadir, MD, PhD, 89 Mika Martikainen, MD, PhD, 90 Vanderci Borges, MD, PhD, 91 Jens Michael Hertz, MD, 92 Laura Brighina, MD, PhD, 93 Mariana Spitz, MD, PhD, 94 Oksana Suchowersky, MD, 95 Olaf Riess, MD, 96 Parimal Das, PhD, 97 Brit Mollenhauer, MD, 98 Emilia M. Gatto, MD, 99 Maria Skaalum Petersen, PhD, 100 Nobutaka Hattori, MD, PhD, 34 Ruey-Meei Wu, MD, PhD, 28 Sergey N. Illarioshkin, MD, PhD, 23 Enza Maria Valente, MD, PhD, 101 Jan O. Aasly, 102,103 Anna Aasly, MSc, 104 Roy N. Alcalay, MD, MS, 10 Avner Thaler, MD, PhD, 105 Matthew J. Farrer, PhD, 106 Kathrin Brockmann, MD, 5 Jean-Christophe Corvol, MD, 107 Christine Klein, MD, 1 *and on behalf of the MJFF Global Genetic Parkinson’s Disease Study Group 1 Institute of Neurogenetics, University of Lübeck, Lübeck, Germany 2 Research Programs, The Michael J. Fox Foundation for Parkinson’s Research, New York, New York, USA 3 Department of Neurology, Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié- Salpêtrière Hospital, Paris, France 4 Sorbonne University, Paris Brain Institute –ICM, Inserm, CNRS, Paris, France 5 Department of Neurodegenerative Diseases, University of Tuebingen, Tuebingen, Baden Wuerttemberg, Germany, Hertie Institute for Clinical Brain Research and German Centre for Neurodegenerative Diseases, Tuebingen, Germany 6 Mongi Ben Hmida National Institute of Neurology, Tunis, Tunisia 7 Laboratory of Early Markers of Neurodegeneration, 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 8 Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel 9 Department of Neurology, Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York, USA 10 Department of Neurology, Columbia University, New York, New York, USA 11 Department of Psychiatry and Psychotherapy and Institute of Neurogenetics, University of Lübeck, Lübeck, Germany 12 Department of Neurology and Institute of Neurogenetics, University of Lübeck, Lübeck, Germany 13 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA 14 Parkinson Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Barcelona, Spain 15 Institute of Biomedical Research and Innovation, National Research Council, Cosenza, Italy 16 Parkinson’s and Movement Disorders Unit, 2nd Department of Neurology of the University of Athens, Attikon Hospital, Haidari, Athens, Greece; Psychiatry Hospital of Attica "Dafni,"Neurology Department, Haidari, Athens, Greece 17 First Department of Neurology, Medical School of the National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece 18 Laboratory of Clinical Pharmacology and Therapeutics, University of Lisbon, Lisbon, Portugal; Instituto de Medicina Molecular Jo˜ ao Lobo Antunes, Faculty of Medicine, University of Lisbon, Lisbon, Portugal 19 Department of Neuroscience and Mental Health, Neurology Department, Hospital de Santa Maria, CHULN, Lisbon, Portugal; Instituto de Medicina Molecular Jo˜ ao Lobo Antunes, Faculty of Medicine, University of Lisbon, Lisbon, Portugal 20 Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy 21 Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Sant’Andrea University Hospital, Rome, Italy 22 Department of Pathology and Cell Biology, Vagelos College of Physicians & Surgeons, Columbia University Irving Medical Center, New Movement Disorders, Vol. 38, No. 2, 2023 287 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 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 23 Department of Neurogenetics, Research Center of Neurology, Moscow, Russia 24 Laborat orio de Genética, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, Instituto de Investigaci on Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain 25 Servicio Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigaci on; Instituto de Investigaci on Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain 26 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain 27 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden 28 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan 29 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 30 Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA 31 Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA 32 Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA 33 Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan 34 Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Bunkyo, Tokyo, Japan 35 Department of Neurology, Biomedical Research Institute IIB-Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain 36 Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK 37 Neurogenetics Research Center, Instituto Nacional de Ciencias Neurologicas, Lima, Peru; Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru 38 Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru 39 Department of Neurology, Chang Gung University, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan 40 Department of Life Science, National Taiwan Normal University, Taipei, Taiwan 41 Movement Disorders Clinic, Department of Neurology, Centro Hospitalar e Universit ario de Coimbra, Coimbra, Portugal 42 Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand 43 Department of Neurology, Christian-Albrechts-Universität, Kiel, Germany 44 Movement Disorder and Neuromodulation Unit, Charité, Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany 45 Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy 46 Department of Neurology, Medical University, Vienna, Austria 47 Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden; Department of Neurology, Skåne University, Lund, Sweden 48 Griffith Institute for Drug Discovery (GRIDD), School of Environment and Science, Griffith University, Brisbane, Queensland, Australia 49 Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland 50 Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa 51 IRCCS Neuromed, Localita‘Camerelle, Pozzilli, Isernia, Italy; Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Urbino, Italy 52 Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA 53 Department of Neurology, NorthShore University HealthSystem, Evanston Illinois and Department of Neurology, University of Chicago, Chicago, Illinois, USA 54 Secci on Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina; Argentine National Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina 55 Department of Neurology, The University of Tokyo, Tokyo, Japan 56 Secci on Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina; Argentine National Scientific and Technological Research Council (CONICET), Argentina; Pontificia Universidad Cat olica Argentina (UCA), Buenos Aires, Argentina 57 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 58 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 59 Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 60 Behavioural Genetics Unit, Department of Genetics, Research Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia 61 Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey 62 Department of Neurology, Medical University in Warsaw, Warsaw, Poland 63 Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey 64 Department of Neurology, University of Health Sciences, Şis¸li Hamidiye Etfal Training and Research Hospital, _ Istanbul, Turkey 65 Hospital Israelita Albert Einstein, S˜ ao Paulo, Brazil; Department of Neurology and Neurosurgery, Universidade Federal de S˜ ao Paulo, S˜ ao Paulo, Brazil 66 DST/NWU Preclinical Drug Development Platform, North-West University, Potchefstroom, North-West, South Africa 67 Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil 288 Movement Disorders, Vol. 38, No. 2, 2023 VOLLSTEDT ET AL 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 68 Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA 69 Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands 70 Department of Neurology, Beth Israel Medical Center, New York, New York, USA; Department of Neurology at Albert Einstein College of Medicine, New York, New York, USA 71 Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway 72 Pacific Parkinson’s Research Centre, Division of Neurology, Department of Medicine, Vancouver, British Columbia, Canada 73 Edmond J. Safra Program in Parkinson’s Disease, Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada 74 Department of Neurology, Pavol Jozef ˇ Saf arik University in Koˇ sice, Koˇ sice, Slovakia; Department of Neurology, University Hospital L. Pasteur, Kosice, Slovakia 75 Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands 76 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg 77 Neurology Department, Ninewells Hospital and Medical School, Dundee, United Kingdom; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK 78 Behavioral and Movement Disorders Section, Ribeir˜ ao Preto Medical School, University of S˜ ao Paulo, Brazil 79 Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China 80 Department of Neurology, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium; MoVeRe Group, GIGA-CRC In Vivo Imaging, University of Liege, Liège, Belgium 81 Medical Genetic Center, Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea 82 Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea 83 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 84 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 85 Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore General Hospital, Singapore, Singapore 86 Department of Neurology, Hospital de Santo Ant onio - Centro Hospitalar Universit ario do Porto, Porto, Portugal; UnIGENe, Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigaç˜ ao e Inovaç˜ ao em Saúde (i3S), Universidade do Porto, Portugal 87 Department of Neurology, University of Szeged, Szeged, Hungary 88 Department for Neurodegeneration, Clinic for Neurology CCS, Belgrade, Serbia 89 Department of Neurology, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel 90 Neurocenter, Turku University Hospital, Turku, Finland; Clinical Neurosciences, Faculty of Medicine, University of Turku, Turku, Finland 91 Department of Neurology and Neurosurgery, Universidade Federal de S˜ ao Paulo, S˜ ao Paulo, Brazil 92 Department of Clinical Genetics, Odense University Hospital, Odense C, Denmark 93 Department of Neurology, Milan Center for Neuroscience, University of Milano-Bicocca/San Gerardo Hospital, Monza, Italy 94 Neurology Service, State University of Rio de Janeiro, Rio de Janeiro, Brazil 95 Department of Medicine, Medical Genetics and Pediatrics, University of Alberta, Edmonton, Alberta, Canada 96 Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany 97 Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India 98 Movement Disorder Paracelsus-Elena-Klinik, Kassel, Germany; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany 99 Movement Disorders, Department of Neurology, Instituto de Neurosciencias Buenos Aires, Buenos Aires, Argentina 100 Centre of Health Science, University of the Faroe Islands, T orshavn, Faroe Islands; Department of Occupational Medicine and Public Health, The Faroese Hospital System, T orshavn, Faroe Islands 101 Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia; Department of Molecular Medicine, University of Pavia, Pavia, Italy 102 Department of Neurology, St. Olavs Hospital, Trondheim, Norway 103 Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway 104 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway 105 Movement Disorders, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel 106 Fixel Institute, Department of Neurology, University of Florida, Gainesville, Florida, USA 107 Sorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Neurology, Paris, France Movement Disorders, Vol. 38, No. 2, 2023 289 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License ABSTRACT: Background:As gene-targeted therapies are increasingly being developed for Parkinson’s disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trialready cohorts is limited. Objective:The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and qualitycontrolled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods:We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA,LRRK2,VPS35,PRKN, PINK1,DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed. Results:We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2,115SNCA,23VPS35,429PRKN, 75 PINK1,13DJ-1, and 1224 GBA)and703were unaffected (ie, 328 LRRK2,32SNCA,3VPS35, 1PRKN,1PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions:Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Key Words: Parkinson’s disease; monogenic PD Rapidly advancing sequencing technologies offer new and cost-effective approaches to increasingly define genetic subtypes of common diseases. An illustrative example is Parkinson’s disease (PD) that can be genetically stratified into subgroups of patients with well-established, albeit individually rare, genetic forms of PD. These are due to pathogenic variants in LRRK2,SNCA,VPS35,PRKN,PINK1, DJ-1,andGBA, the latter acting as the strongest known genetic risk factor of PD. 1 As a relatively common disease with only up to 10% accounting for genetic subtypes, 2 PD is not considered a hereditary disorder per se. As genetic testing is not a commonorevenstandardelement of the diagnostic workup due to the absence of gene-specific therapies, it is currently most often performed in a research setting. However, scientific interest in publications on clinical-genetic screening studies of well-established PD genes is continuously declining, whereas the advent of first gene-targeted therapies 3,4 immediately calls for well-characterized clinical trial-ready cohorts of variant carriers. To address the lack of systematic data resources on monogenic PD, our team established the Movement Disorder Society Genetic Mutation Database (MDSGene, www.mdsgene.org). Although the actual number of PD patients with a genetic cause is estimated at 650,000, ie, 10% of the 0.65 million PD patients worldwide, 2,5 only a small fraction (n =2120) of monogenic PD patients with individual patient information are contained in the international medical literature published in the English language. Availability of quantitative clinical data is limited, and there is a strong focus on motor symptoms and on select ethnicities in the literature. 6,7 However, frequency, clinical expression, and penetrance of genetic variants may vary considerably across different populations and ethnicities. 8 For example, a landmark study comparing patients with the same pathogenic variant in LRRK2 in a Norwegian and a Tunisian sample revealed a much higher proportion of affected variant carriers among the Tunisians than the Norwegians at a 60-year age cut-off. Knowing, understanding, and considering these population-specificfactors facilitate the composition of study samples tailored to specific research questions or clinical trials. The MDSGene resource served to systematically identify researchers following monogenic PD patients, 98% of whom expressed interest to jointly build up the MJFF Global Monogenic PD Study Group 8 to address the following aims: (1) establish an international cohort of individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; (3) further promote the collaboration of researchers in the field of monogenic PD with a view toward demographic, clinical, and genetic stratification of patients for gene-targeted clinical trials. 290 Movement Disorders, Vol. 38, No. 2, 2023 VOLLSTEDT ET AL 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Patients and Methods Data Collection Process To collect individual-level data on the patients that had been reported to us in the first phase of the MJFF Global Genetic PD Project, 9 we developed an online survey. We focused on carriers of variants in genes associated with monogenic PD (LRRK2,SNCA, VPS35,PRKN,PINK1,DJ-1), but also included variants in the strongest genetic risk factor for PD, ie, GBA. Variants in other PD-linked genes were not included in the analyses (Appendix S1: Table 1). We collected detailed genetic information alongside demographic data, disease status, pedigrees, motor scales, nonmotor scales, risk factors, and medication (31 items, Appendix S1: Table 2). All members of the MJFF Global Genetic PD Study Group were invited to participate, and new members were included upon recommendation or request. The survey was open from October 2018 to March 2019, including two rounds of reminders and additional customized extensions of the deadline upon request by several study centers. After 1 year, from September to October 2020, we reopened the survey for its first annual update and invited members of the study group to update their data and to add newly identified individuals with PD-linked variants. An important part of the data collection process was the communication with study centers to keep them informed about the project, to address any questions regarding the survey, and to ensure a high quality of the collected data. Nomenclature The nomenclature of the genes follows the recommendations of the HUGO Gene Nomenclature Committee (www.genenames.org) with the exception of PARK7 that we refer to as DJ-1. Variants are annotated corresponding to the following transcript IDs: LRRK2: NM_198578.3, SNCA: NM_000345.3, VPS35: NM_018206.5, PRKN: NM_004562.2, PINK1: NM_032409.2, DJ-1: NM_001123377.1, GBA: NM_000157.3. Inclusion and Exclusion Criteria All registered variant carriers underwent thorough quality checks regarding both clinical and genetic data (Fig. 1). The mandatory minimal data set for eligible samples comprised information on the genetic variant, sex, disease status, and age at onset. In case of any missing or contradictory information, we asked the submitting researcher for clarification. Duplicate submissions and samples with an unresolved clinical or genetic status were excluded from further analyses. Variants in LRRK2,SNCA,VPS35,PRKN,PINK1, and DJ-1 were excluded if they had a minor allele frequency (MAF) ≥1% based on the ethnicity with the maximal MAF in the gnomAD Browser v.2.1.1 (https:// gnomad.broadinstitute.org), dbSNP (http://www.ncbi. nlm.nih.gov/snp/). Individuals with pathogenic variants in more than one PD gene were excluded, but those harboring an additional known risk variant in LRRK2 (p.R1628P) or GBA (p.R83C, p.E365K, p.T408M, p.N409S, p.L483P, p.V499L, p.R535H) were included in our analyses. For GBA, we only included the four most frequent variants (p.E365K, p.T408M, p. N409S, p.L483P). Although p.N409S and p.L483P are considered pathogenic variants due to their causal link to Gaucher’s disease and are rare (<0.5% globally according to gnomAD), p.E365K and p.T408M are classified as PD risk variants with a global MAF of >0.5%. 10 Analyses for GBA exclude digenic variant carriers; that is, all included individuals have been reported to carry one variant in GBA only. FIG. 1. Number of cases registered in the online survey and number of cases excluded after quality control and evaluating pathogenicity including reasons for exclusion. Movement Disorders, Vol. 38, No. 2, 2023 291 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pathogenicity Scoring Variants of eligible individuals underwent pathogenicity scoring. The presumed pathogenicity of a genetic variant was taken from MDSGene for previously scored variants or assessed using MDSGene criteria, 6 (https://mdsgene.org/methods). The score is based on four items, including information on segregation, variant frequency in patients and controls, in-silico prediction using the Combined Annotation Dependent Depletion (CADD) score (http://cadd.gs.washington. edu/), and functional evidence extracted from published in-vitro and in-vivo studies. Based on these categories, a pathogenicity score was devised, and variants were classified as definitely pathogenic, probably pathogenic, possibly pathogenic, or benign. 6 The MDSGene pathogenicity scoring was designed for causative, monogenic causes but is not applicable to variants with an MAF >1% such as risk variants in GBA. Statistical Analyses All statistical analyses were performed using SPSS 26.0.0.0 (IBM, Armonk, NY). For median values, the interquartile range (IQR) is displayed in parentheses. Results The MJFF Global Genetic PD Cohort To establish the cohort, we contacted researchers from 232 centers all over the world and obtained data from 92 centers in 42 countries. In total, 5571 cases were registered in our database, of whom 3888 were included in our analyses (1683 cases were excluded; for details, see Fig. 1). Of these, 3175 had PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN,75PINK1,3DJ-1, and 1224 GBA) and 703 were unaffected individuals (ie, 328 LRRK2,32SNCA,3VPS35,1PRKN,1PINK1, and 338 GBA). These numbers exclude monoallelic carriers of variants in PRKN (PD: n =217, unaffected: n=89), PINK1 (PD: n =56, unaffected: n =45), and DJ-1 (PD: n =4, unaffected: n =3). Forty-four individuals carried pathogenic variants in other genes linked to forms of parkinsonism or related movement disorders (Appendix S1: Table 1). Individuals originated from 65 countries worldwide (Fig. 2A), and the predominant ethnicity was white (90%) (Fig. 2B). The break-up of centers per continent is as follows: Europe: n =48; Asia: n =15; North America: n =13; South America: n =8; Australia: n =3; Africa: n =2 (Fig. 3A). About 75% of the world population (5.9 billion) inhabits the countries of origin included in our cohort, whereas the countries of 25% of the world population (2 billion individuals) are not yet represented in the MJFF Global Genetic PD Cohort (Fig. 3B). Data Completeness Per inclusion criteria, basic data such as age at onset were complete for all participants. Availability of clinical data across the cohort ranged from more basic features (77% for disease duration) to more complex assessment of nonmotor symptoms (41% for cognition). Motor scales were available for 51% (MDSUPDRS or UPDRS) and 47% (Hoehn and Yahr Stage) of the individuals with PD, respectively. Information on medication was reported for 60% of the sample, and risk factor data (smoking, caffeine) were available for a subset (20%) of individuals. Gene-Specific Findings The median age at onset of PD was younger in individuals with variants in recessively inherited genes than in those with variants in dominantly inherited genes and GBA (Fig. 4and Appendix S1: Tables 4–6). Gene-specificfindings for dominantly (LRRK2, SNCA,VPS35) and recessively inherited genes (PRKN, PINK1,DJ-1) and GBA are summarized in the following paragraphs (Appendix S1: Tables 4–8; Supplementary Information 1–10; Figs. 7–49): For details on the genetic spectrum, see Appendix S1: Figures 1–6. LRRK2 A total of 1308 individuals with PD (50% women) and 328 unaffected individuals (54% women) with variants in LRRK2 were registered. Most participants were white (93%), including individuals who identify as Berber (20%) and Ashkenazi Jewish (17%). The most common countries of origin were Tunisia (20%), Spain (14%), and Israel (11%). The median age at onset of PD was 57 years (interquartile range [IQR]: 48–65 years) with a predominantly late onset (>40 years, n =1167, 89%) and only a small fraction of patients with an early onset (20–40 years, n=141, 11%). The median disease duration at the time of inclusion was 8 years (4–14, 9% missing data). Fortyeight percent of the individuals with PD and 89% of unaffected individuals reported a family history of PD. SNCA We obtained data on 147 individuals with variants in SNCA (115 with PD [52% women], 32 unaffected [56% women]). The majority were white (97%), and 45% originated from Greece. The median age at onset was 45 years (IQR: 38–52 years), and most patients had a late onset of PD (>40 years, n =79, 69%), but early onset was also reported (20– 40 years, n =36, 31%). The median disease duration at the time of inclusion was 6 years (IQR: 3–9 years, 12% missing data). Eighty-nine percent of the PD cases and 100% of the unaffected individuals reported a family history of PD. 292 Movement Disorders, Vol. 38, No. 2, 2023 VOLLSTEDT ET AL 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License VPS35 Twenty-six individuals had variants in VPS35 (23 individuals with PD [61% women] and three unaffected individuals [33% women]). All individuals were white, and the most common countries of origin were Germany (27%), France (19%), and Austria (15%). The median age at onset was 48 years (44–56 years), 21 individuals had a late onset (>40 years, 91%), and FIG. 2. (A) Reported country of origin of all samples (with and without Parkinson’s disease [PD]). Information missing for 941 individuals (22%). Other countries of origin included (all at <1%): Armenia, Argentina, Australia, Austria, Azerbaijan, Belgium, Bolivia, Canada, China, Czech Republic, Denmark, Ecuador, Estonia, Faroe Islands, Finland, Guadeloupe, Hungary, India, Indonesia, Jersey, Republic of Korea, Lebanon, Libya, Luxembourg, Malaysia, Mexico, Morocco, Netherlands, Peru, Philippines, Pakistan, Saudi Arabia, Serbia, Singapore, Slovakia, South Africa, Sudan, Switzerland, Thailand, Tonga, Ukraine, Venezuela, Vietnam. (B) Reported ethnicity of all samples (with and without PD). Other ethnicities/combinations reported in </=2% are summarized in “Mixed/other.” Movement Disorders, Vol. 38, No. 2, 2023 293 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License two had an early onset of PD (20–40 years, 9%). The disease duration was 11 years (5–15). Ninety percent of the individuals with PD and 67% of unaffected individuals reported a family history of PD. PRKN Our cohort includes 646 individuals with PD (50% women) and 90 unaffected individuals (51% women) with variants in PRKN. Of these, 431 patients carried biallelic variants and were included in the following analyses. Seventy-eight percent were white, and the most commonly reported countries of origin were France (23%) and Italy (12%). The median age at onset of PD was 32 (IQR: 23–38 years), and most patients had an early onset (20–40 years, n =283, 65.5%); late onset was reported for 80 patients (>40 years, 18.5%), whereas 68 had a juvenile onset (<20 years, 16%). The median disease duration was 15 years (8–25). Fiftythree percent of the PD patients reported affected family members (12% of missing data). FIG. 3. (A) Countries of origin of individuals in the MJFF Global Genetic PD Cohort. This figure displays numbers for reported individuals with variants in Parkinson’s disease (PD)-associated genes (including LRRK2,SNCA,VPS35,PRKN,PINK1,DJ-1,GBA, and also monoallelic carriers of variants in PRKN,PINK1, and DJ-1) with and without a diagnosis of PD (numbers after the slash represent subjects without PD). Missing data for 941 subjects (22%), mixed origin for six subjects (0.001%). Country names are abbreviated using the two-letter codes defined in ISO-3166-1 alpha-2. (B) Countries harboring centers that submitted individuals to be included in the MJFF Global Genetic PD Cohort. This figure highlights countries with centers participating in the MJFF Global Genetic PD Project in blue, and countries shaded in gray are not yet reflected in the cohort (for details, see Appendix S1: Supplement 3). 294 Movement Disorders, Vol. 38, No. 2, 2023 VOLLSTEDT ET AL 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Péter Klivényi, Department of Neurology, University of Szeged, Szeged, Hungary Vladimir S. Kostic, Department for Neurodegeneration, Clinic for Neurology CCS, Belgrade, Serbia Dariusz Koziorowski, Department of Neurology, Medical University in Warsaw, Warsaw, Poland Rejko Krüger, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg; Transversal Translational Medicine, Luxembourg Institute of Health (LIH), Strassen, Luxembourg; Parkinson Research Clinic, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg Andrea A. Kühn, Movement Disorder and Neuromodulation Unit, Charité, Universitätsmedizin Berlin, Department of Neurology, Campus Mitte, Berlin, Germany Gregor Kuhlenbäumer, Department of Neurology, Christian-Albrechts-Universität, Kiel, Germany Ming-Che Kuo, Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan Anthony E. Lang, Edmond J. Safra Program in Parkinson’s Disease, Division of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada Guey-Jen Lee-Chen, Department of Life Science, National Taiwan Normal University, Taipei, Taiwan Suzanne Lesage, Sorbonne University, Paris Brain Institute—ICM, Inserm, CNRS, Paris, France Jia Lun Lim, Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Shen-Yang Lim, 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, Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan Katja Lohmann, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany Timothy Lynch, 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 Karen Marder, Department of Neurology, Taub Institute for Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York, USA Katerina Markopoulou, Department of Neurology, NorthShore University HealthSystem, Evanston, Illinois, USA; Department of Neurology, University of Chicago, Chicago, Illinois, USA Mika Martikainen, Neurocenter, Turku University Hospital, Turku, Finland; Clinical Neurosciences, Faculty of Medicine, University of Turku, Turku, Finland Patrick May, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur- Alzette, Luxembourg Allan McCarthy, The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland & Department of Neurology, The Adelaide and Meath Hospital, Dublin, Ireland George D. Mellick, Griffith Institute for Drug Discovery (GRIDD), School of Environment and Science, Griffith University, Brisbane, Queensland, Australia Manuel Menéndez-Gonz alez, Servicio Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigaci on; Instituto de Investigaci on Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain Marcelo Merello, Secci on Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina; Argentine National Scientific and Technological Research Council (CONICET), Argentina; Pontificia Universidad Cat olica Argentina (UCA), Argentina Pablo Mir, Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain Anat Mirelman, Laboratory of Early Markers of Neurodegeneration, 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 Brit Mollenhauer, Movement Disorder Paracelsus- Elena-Klinik, Kassel, Germany; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany Hugo Morales Briceno, Movement Disorders Unit, Department of Neurology, Westmead Hospital, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia Ana Morgadinho, Movement Disorders Clinic, Department of Neurology, Universit ario de Coimbra, Coimbra, Portugal Huw Morris, 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 Alexandra Mosejova, Department of Neurology, Pavol Jozef ˇ Saf arik University in Koˇ sice, Koˇ sice, Slovakia Movement Disorders, Vol. 38, No. 2, 2023 301 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Kenya Nishioka, Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan Özgür Öztop Çakmak, Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey Diana A. Olszewska, 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 Avi Orr-Urtreger, The Genomic Research Laboratory for Neurodegeneration, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Sinthuja Pachchek, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Eschsur-Alzette, Luxembourg Shalini Padmanabhan, Research Programs, The Michael J. Fox Foundation for Parkinson’s Research, New York, New York, USA Maria Teresa Periñ an, Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain Simona Petrucci, Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy; Sant’Andrea University Hospital, Rome, Italy Marcia M. G. Pimentel, Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil Radha Procopio, Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy Teeratorn Pulkes, Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Rajthevi, Bangkok, Thailand Andreas Puschmann, Department of Neurology, Clinical Sciences, Lund University, Lund, Sweden; Department of Neurology, Skåne University, Lund, Sweden Caroline Ran, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden Olaf Riess, Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany Owen A. Ross, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA Malco Rossi, Secci on Movimientos Anormales, Departamento de Neurociencias, Fleni, Buenos Aires, Argentina; Argentine; National Scientific and Technological Research Council (CONICET), Buenos Aires, Argentina Javier Ruiz-Martinez, Neuroscience Area, Biodonostia Research Institute, San Sebastian, Gipuzkoa, Spain; Department of Neurology, University Hospital Donostia, San Sebastian, Gipuzkoa, Spain Esther M. Sammler, Neurology Department, Ninewells Hospital and Medical School, Dundee, United Kingdom; MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, United Kingdom Jo˜ ao Santos Pereira, Movement Disorders Section, Neurology Service, Pedro Ernesto University Hospital, State University of Rio de Janeiro, Rio de Janeiro, Brazil Wataru Satake, Department of Neurology, The University of Tokyo, Tokyo, Japan Rachel Saunders-Pullman, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA Susen Schaake, Maria Skaalum Petersen, Centre of Health Science, University of the Faroe Islands, T orshavn, Faroe Islands; Department of Occupational Medicine and Public Health, The Faroese Hospital System, Faroe Islands Matej Skorvanek, Department of Neurology, Pavol Jozef ˇ Saf arik University in Koˇ sice, Koˇ sice, Slovakia; Department of Neurology, University Hospital L. Pasteur, Kosice, Slovakia Leonidas Stefanis, First Department of Neurology, Medical School of the National and Kapodistrian University of Athens, Eginition Hospital, Athens, Greece Alexandra I. Soto-Beasley, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA M ario Sousa, Movement Disorders Clinic, Department of Neurology, Universit ario de Coimbra, Coimbra, Portugal Mariana Spitz, Neurology Service, State University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil Oksana Suchowersky, Department of Medicine, Medical Genetics and Pediatrics, University of Alberta, Edmonton, Alberta, Canada Carolyn M. Sue, 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 Ai Huey Tan, 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, Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore General Hospital, Singapore, Singapore Avner Thaler, Movement Disorders, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel-Aviv University, Tel- Aviv, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel Fatih Tepgeç, Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul, Turkey 302 Movement Disorders, Vol. 38, No. 2, 2023 VOLLSTEDT ET AL 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Pichet Termsarasab, Division of Neurology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Rajthevi, Bangkok, Thailand Christelle Tesson, Sorbonne University, Paris Brain Institute—ICM, Inserm, CNRS, Paris, France Tatsushi Toda, The University of Tokyo, Tokyo, Japan Mathias Toft, Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway Eduardo Tolosa, Parkinson Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Centro de Investigaci on Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII) Barcelona, Spain Luis Torres-Ramirez, Movement Disorders Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru Vitor Tumas, Behavioral and Movement Disorders Section, Ribeir˜ ao Preto Medical School, University of S˜ ao Paulo, Brazil Oya Uyguner, Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul, Turkey Enza Maria Valente, Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia; Department of Molecular Medicine, University of Pavia, Pavia, Italy Bart van de Warrenburg, Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Centre, Nijmegen, The Netherlands Marie Vidailhet, Sorbonne University, Paris Brain Institute—ICM, Inserm, CNRS, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Department of Neurology, Paris, France Eva-Juliane Vollstedt, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany Ronald L. Walton, Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA Cheryl Waters, 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 Caroline H. Williams-Gray, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom Juliane Winkelmann, 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 Yih-Ru Wu, Department of Neurology, Chang Gung University, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan Isabel Wurster, 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 Zbigniew K. Wszolek, Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA Ruey-Meei Wu, Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; Department of Neurology, National Taiwan University College of Medicine, Taipei, Taiwan Bao-rong Zhang, Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China Alexander Zimprich, Department of Neurology, Medical University, Vienna, Austria Supporting Data Additional Supporting Information may be found in the online version of this article at the publisher’s web-site. Supporting Data Additional Supporting Information may be found in the online version of this article at the publisher’s web-site. Movement Disorders, Vol. 38, No. 2, 2023 303 THE MJFF GLOBAL GENETIC PD COHORT 15318257, 2023, 2, Downloaded from https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29288 by Universidad De Sevilla, Wiley Online Library on [05/02/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License