Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
Jonggeol Jeffrey Kim(National Institutes of Health), Dan Vitale(National Institutes of Health), Diego Véliz Otani(University of Maryland, Baltimore), Michelle Mulan Lian(Agency for Science, Technology and Research), Karl Heilbron(23andMe (United States)), Stella Aslibekyan(23andMe (United States)), Adam Auton(23andMe (United States)), Elizabeth Babalola(23andMe (United States)), Robert K. Bell(23andMe (United States)), Jessica Bielenberg(23andMe (United States)), Katarzyna Bryc(23andMe (United States)), Emily Bullis(23andMe (United States)), Paul Cannon(23andMe (United States)), Daniella Coker(23andMe (United States)), Gabriel Cuéllar-Partida(23andMe (United States)), Devika Dhamija(23andMe (United States)), Sayantan Das(23andMe (United States)), Sarah L. Elson(23andMe (United States)), Nicholas Eriksson(23andMe (United States)), Teresa Filshtein(23andMe (United States)), Alison Fitch(23andMe (United States)), Kipper Fletez‐Brant(23andMe (United States)), Pierre Fontanillas(23andMe (United States)), Will Freyman(23andMe (United States)), Julie M. Granka(23andMe (United States)), Alejandro Hernandez(Universidad de Costa Rica), Barry Hicks(23andMe (United States)), David A. Hinds(23andMe (United States)), Ethan M. Jewett(23andMe (United States)), Yunxuan Jiang(23andMe (United States)), Katelyn Kukar(23andMe (United States)), Alan Kwong(23andMe (United States)), Keng‐Han Lin(23andMe (United States)), Bianca A. Llamas(23andMe (United States)), Maya Lowe(23andMe (United States)), Jey C. McCreight(23andMe (United States)), Matthew H. McIntyre(23andMe (United States)), Steven J. Micheletti(23andMe (United States)), Meghan E. Moreno(23andMe (United States)), Priyanka Nandakumar(23andMe (United States)), Dominique T. Nguyen(Hue University), Elizabeth S. Noblin(23andMe (United States)), Jared O’Connell(23andMe (United States)), Aaron A. Petrakovitz(23andMe (United States)), G. David Poznik(23andMe (United States)), Alexandra Reynoso(23andMe (United States)), Madeleine Schloetter(23andMe (United States)), Morgan Schumacher(23andMe (United States)), Anjali J. Shastri(23andMe (United States)), Janie F. Shelton(23andMe (United States)), Jingchunzi Shi(23andMe (United States)), Suyash Shringarpure(23andMe (United States)), Qiaojuan Jane Su(23andMe (United States)), Susana A. Tat(23andMe (United States)), Christophe Toukam Tchakouté(23andMe (United States)), Vinh Tran(23andMe (United States)), Joyce Y. Tung(23andMe (United States)), Xin Wang(23andMe (United States)), Wei Wang(23andMe (United States)), Catherine H. Weldon(23andMe (United States)), Peter Wilton(23andMe (United States)), Corinna D. Wong(23andMe (United States)), Hirotaka Iwaki(National Institutes of Health), Julie Lake(National Institutes of Health), Caroline Warly Solsberg(University of California, San Francisco), Hampton L. Leonard(National Institutes of Health), Mary B. Makarious(National Institutes of Health), Eng‐King Tan(Duke-NUS Medical School), Andrew Singleton(National Institutes of Health), Sara Bandrés‐Ciga(National Institutes of Health), Alastair J. Noyce(Queen Mary University of London), the Global Parkinson’s Genetics Program (GP2)(Hospital de Niños de la Santísima Trinidad), Emilia Gatto(Hospital Ramos Mejía), Marcelo Kauffman(Hospital Ramos Mejía), Samson Khachatryan, Zaruhi Tavadyan(Neuroscience Research Australia), Claire E. Shepherd(Anzac Research Institute), Julie Hunter(Garvan Institute of Medical Research), Kishore R. Kumar(Garvan Institute of Medical Research), Melina Ellis(QIMR Berghofer Medical Research Institute), Miguel E. Rentería(Murdoch University), Sulev Kõks(Murdoch University), Alexander Zimprich(Universidade Federal do Rio Grande do Sul), Artur Francisco Schumacher Schuh(Universidade Federal do Rio Grande do Sul), Carlos Roberto de Mello Rieder(Universidade Federal do Rio Grande do Sul), Paula Saffie Awad(Universidade Federal do Rio Grande do Sul), Vítor Tumas(Universidade Federal de Minas Gerais), Sarah Camargos(Universidade Federal de Minas Gerais), Edward A. Fon(Montreal Neurological Institute and Hospital), Oury Monchi(Institut Universitaire de Gériatrie de Montréal), Ted Fon(McGill University), Benjamin Pizarro Galleguillos(Fundación Chile), Marcelo Miranda(Fundación Chile), M. Leonor Bustamante(University of Chile), Patricio Olguı́n(University of Chile), Pedro Chaná(Central South University), Beisha Tang(Central South University), Huifang Shang(Central South University), Jifeng Guo(Central South University), Piu Chan(Capital Medical University), Wei Luo(Universidad Nacional de Colombia), Gonzálo Arboleda(Universidad Nacional de Colombia), Jorge Orozc(Universidad de Antioquia), Marlene Jiménez-Del-Río(Universidad de Costa Rica), Alvaro Hernandez(Universidad de Costa Rica), Mohamed Salama(Beni-Suef University), Walaa A. Kamel(Beni-Suef University), Yared Z. Zewde(Addis Ababa University), Alexis Brice(Sorbonne Université), Jean‐Christophe Corvol(Sorbonne Université), Ana Westenberger(German Center for Neurodegenerative Diseases), Anastasia Illarionova(German Center for Neurodegenerative Diseases), Brit Mollenhauer(Universitätsmedizin Göttingen), Christine Klein(University of Lübeck), Eva‐Juliane Vollstedt(LMU Klinikum), Franziska Hopfner(LMU Klinikum), Günter U. Höglinger(LMU Klinikum), Harutyun Madoev(University of Lübeck), Joanne Trinh(University of Lübeck), Johanna Junker(University of Lübeck), Katja Lohmann(University of Lübeck), Lara M. Lange(University Hospital Schleswig-Holstein), Manu Sharma(Johannes Gutenberg University Mainz), Sergiu Groppa(Johannes Gutenberg University Mainz), Thomas Gasser(German Center for Neurodegenerative Diseases), Zih‐Hua Fang(University of Ghana), Albert Akpalu(University of Ghana), Georgia Xiromerisiou(University of Thessaly), Georgios Hadjigorgiou(University of Thessaly), Ioannis Dagklis(Ionian University), Ioannis Tarnanas(Ionian University), Leonidas Stefanis(Biomedical Research Foundation of the Academy of Athens), María Stamelou(University of Thessaly), Efthymios Dadiotis(University of Thessaly), Alex Medina(Universidad Metropolitana de Honduras), Germaine Hiu-Fai Chan(Hong Kong University of Science and Technology), Nancy Y. Ip(Hong Kong University of Science and Technology), Nelson Yuk-Fai Cheung(Hong Kong University of Science and Technology), Phillip Chan(Capital Medical University), Xiaopu Zhou(Hong Kong University of Science and Technology), Asha Kishore(Sree Chitra Thirunal Institute for Medical Sciences and Technology), K. P. Divya(Sree Chitra Thirunal Institute for Medical Sciences and Technology), Pramod Kumar Pal(Manipal Hospital), Prashanth Lingappa Kukkle(Manipal Hospital), Roopa Rajan(Nizam's Institute of Medical Sciences), Rupam Borgohain(Nizam's Institute of Medical Sciences), Mehri Salari(Magna Graecia University), Andrea Quattrone(University of Pavia), Enza Maria Valente(University of Pavia), Lucilla Parnetti(University of Pavia), Micol Avenali(University of Rome Tor Vergata), Tommaso Schirinzi(University of Rome Tor Vergata), Manabu Funayama(Juntendo University), Nobutaka Hattori(Jikei University School of Medicine), Tomotaka Shiraishi(Jikei University School of Medicine), Altynay Karimova, Gulnaz Kaishibayeva(Kyrgyz State Medical Academy), Cholpon Shambetova(Kyrgyz State Medical Academy), Rejko Krüger(University of Luxembourg), Ai Huey Tan(University of Malaya), Azlina Ahmad‐Annuar(University of Malaya), Mohamed Ibrahim Norlinah(National University of Malaysia), Nor Azian Abdul Murad(University Kebangsaan Malaysia Medical Centre), Shahrul Azmin(University Kebangsaan Malaysia Medical Centre), Shen‐Yang Lim(University of Malaya), Wael Mohamed(University of Malaya), Yi Wen Tay(University of Malaya), Daniel Martínez-Ramírez(Instituto Nacional de Neurología y Neurocirugía), Mayela Rodríguez‐Violante(Instituto Nacional de Neurología y Neurocirugía), Paula Reyes‐Pérez(Mongolian National University of Medical Sciences), Bayasgalan Tserensodnom(Tribhuvan University), Rajeev Ojha(Tribhuvan University), Tim Anderson(University of Otago), Toni L. Pitcher(University of Lagos), Arinola Sanyaolu(University of Lagos), Njideka Okubadejo(University of Lagos), Oluwadamilola O. Ojo(University of Lagos), Jan Aasly(Oslo University Hospital), Lasse Pihlstrøm(Oslo University Hospital), Manuela Tan(Oslo University Hospital), Shoaib Ur-Rehman(University of Maryland, Baltimore), Diego Véliz-Otani(University of Maryland, Baltimore), Mario Cornejo‐Olivas(Universidad Científica del Sur), Maria Leila M. Doquenia, Raymond L. Rosales(University of Puerto Rico System), Ángel Viñuela(University of Puerto Rico System), Е. А. Яковенко(King Faisal Specialist Hospital & Research Centre), Bashayer Al Mubarak(King Faisal Specialist Hospital & Research Centre), Muhammad Umair(King Abdullah International Medical Research Center), Ferzana Amod(Stellenbosch University), Jonathan Carr(Stellenbosch University), Soraya Bardien(Stellenbosch University), Beomseok Jeon(Severance Hospital), Yun Joong Kim(Severance Hospital), Esther Cubo(University Hospital Mútua de Terrassa), Ignacio Álvarez(University Hospital Mútua de Terrassa), Janet Hoenicka(Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol), Katrin Beyer(Instituto de Biomedicina de Sevilla), María Teresa Periñán(Instituto de Biomedicina de Sevilla), Pau Pástor(University of Khartoum), Sarah El-Sadig(University of Khartoum), Kajsa Brolin(University of Bern), Christiane Zweier(University of Bern), Gerd Tinkhauser(University of Bern), Paul Krack(University of Bern), Chin‐Hsien Lin(Taoyuan Chang Gung Memorial Hospital), Hsiu-Chuan Wu(National Taiwan University), Pin‐Jui Kung(National Taiwan University), Ruey‐Meei Wu(Taoyuan Chang Gung Memorial Hospital), Yih‐Ru Wu(Taoyuan Chang Gung Memorial Hospital), Rim Amouri(National Institute of Neurology Mongi-Ben Hamida), Samia Ben Sassi(Koç University), A. Nazl Başak(Koç University), Gençer Genç(Koç University), Özgür Öztop Çakmak(Koç University), Sibel Ertan(Koç University), Alejandro Martínez-Carrasco(National Hospital for Neurology and Neurosurgery), Anette Schrag(National Hospital for Neurology and Neurosurgery), Anthony H.V. Schapira(National Hospital for Neurology and Neurosurgery), Camille Carroll(Parkinson's UK), Claire Bale(Parkinson's UK), Donald G. Grosset(National Hospital for Neurology and Neurosurgery), Eleanor J. Stafford(National Hospital for Neurology and Neurosurgery), Henry Houlden(National Hospital for Neurology and Neurosurgery), Huw R. Morris(National Hospital for Neurology and Neurosurgery), John Hardy(National Hospital for Neurology and Neurosurgery), Kin Y. Mok(National Hospital for Neurology and Neurosurgery), Mie Rizig(National Hospital for Neurology and Neurosurgery), Nicholas Wood(National Hospital for Neurology and Neurosurgery), Nigel Williams(National Hospital for Neurology and Neurosurgery), Olaitan Okunoye(University of London), Patrick A. Lewis(University of London), Rauan Kaiyrzhanov(National Hospital for Neurology and Neurosurgery), Rimona S. Weil(University of Bristol), Seth Love(University of Bristol), Simon Stott(Parkinson's UK), Simona Jasaityte(Queen Mary University of London), Sumit Dey(Queen Mary University of London), Vida Obese(National Hospital for Neurology and Neurosurgery), Alberto J. Espay(Michael J. Fox Foundation), Alyssa O’Grady(University of Georgia), Andrew K. Sobering(University of Georgia), Bernadette Siddiqi(Michael J. Fox Foundation), Bradford Casey(Michael J. Fox Foundation), Brian Fiske(Michael J. Fox Foundation), Cabell Jonas(Washington University in St. Louis), Carlos Cruchaga(National Institutes of Health), Caroline B. Pantazis(National Institutes of Health), Charisse Comart(Michael J. Fox Foundation), Claire Wegel(Indiana University Bloomington), Deborah A. Hall(National Institutes of Health), Dena Hernández(National Institutes of Health), Ejaz Shiamim(Kaiser Permanente), Ekemini Riley(National Institutes of Health), Faraz Faghri(National Institutes of Health), Geidy E. Serrano(Banner Sun Health Research Institute), Honglei Chen(Cleveland Clinic), Ignácio F. Mata(Northwestern University), Ignacio Juan Keller Sarmiento(Northwestern University), Jared Williamson(Kaiser Permanente), Joseph Jankovic(Baylor College of Medicine), Joshua Shulman(Baylor College of Medicine), J Solle(Michael J. Fox Foundation), Kaileigh Murphy(University of Miami), Karen Nuytemans(Beth Israel Deaconess Medical Center), Karl Kieburtz(Beth Israel Deaconess Medical Center), Katerina Markopoulou(NorthShore University HealthSystem), Kenneth Marek(National Institutes of Health), Kristin Levine(National Institutes of Health), Lana M. Chahine(University of Pittsburgh), Laura Ibáñez(National Institutes of Health), Laurel A. Screven(National Institutes of Health), Lauren Ruffrage(University of Maryland, Baltimore), Lisa M. Shulman(University of Maryland, Baltimore), Luca Marsili(Michael J. Fox Foundation), Maggie Kuhl(Michael J. Fox Foundation), Marissa Dean(National Institutes of Health), Mathew J. Koretsky(Northwestern University), Megan J. Puckelwartz(Northwestern University), Miguel Inca‐Martinez(Cleveland Clinic), Naomi Louie(Northwestern University), Niccolò E. Mencacci(Northwestern University), Roger L. Albin(University of Michigan), Roy N. Alcalay(James J. Peters VA Medical Center), Ruth Walker(Michael J. Fox Foundation), Sohini Chowdhury(Michael J. Fox Foundation), Sonya B. Dumanis(Northwestern University), Steven Lubbe(Northwestern University), Tao Xie(University of Illinois Chicago), Tatiana M. Foroud(Banner Sun Health Research Institute), Thomas Beach(Michael J. Fox Foundation), Todd Sherer(National Institutes of Health), Yeajin Song(National Institutes of Health), Duan Nguyen(Hue University), Toan Nguyen(University of Zambia), Masharip Atadzhanov(National Institutes of Health), Cornelis Blauwendraat(National Institutes of Health), Mike A. Nalls(Agency for Science, Technology and Research), Jia Nee Foo(Agency for Science, Technology and Research), Ignácio F. Mata(Cleveland Clinic Lerner College of Medicine)
Cited by 249Open Access
Abstract
Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.
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