Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Authors: Jonggeol Jeffrey Kim, Dan Vitale, Diego Véliz Otani, Michelle Mulan Lian, Karl Heilbron, Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Paul Cannon, Daniella Coker, Gabriel Cuéllar-Partida, Devika Dhamija, Sayantan Das, Sarah L. Elson, Nicholas Eriksson, Teresa Filshtein, Alison Fitch, Kipper Fletez‐Brant, Pierre Fontanillas, Will Freyman, Julie M. Granka, Alejandro Hernandez, Barry Hicks, David A. Hinds, Ethan M. Jewett, Yunxuan Jiang, Katelyn Kukar, Alan Kwong, Keng‐Han Lin, Bianca A. Llamas, Maya Lowe, Jey C. McCreight, Matthew H. McIntyre, Steven J. Micheletti, Meghan E. Moreno, Priyanka Nandakumar, Dominique T. Nguyen, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petrakovitz, G. David Poznik, Alexandra Reynoso, Madeleine Schloetter, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Qiaojuan Jane Su, Susana A. Tat, Christophe Toukam Tchakouté, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Corinna D. Wong, Hirotaka Iwaki, Julie Lake, Caroline Warly Solsberg, Hampton L. Leonard, Mary B. Makarious, Eng‐King Tan, Andrew Singleton, Sara Bandrés‐Ciga, Alastair J. Noyce, the Global Parkinson’s Genetics Program (GP2), Emilia Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E. Shepherd, Julie Hunter, Kishore R. Kumar, Melina Ellis, Miguel E. Rentería, Sulev Kõks, Alexander Zimprich, Artur Francisco Schumacher Schuh, Carlos Roberto de Mello Rieder, Paula Saffie Awad, Vítor Tumas, Sarah Camargos, Edward A. Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, M. Leonor Bustamante, Patricio Olguı́n, Pedro Chaná, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzálo Arboleda, Jorge Orozc, Marlene Jiménez-Del-Río, Alvaro Hernandez, Mohamed Salama, Walaa A. Kamel, Yared Z. Zewde, Alexis Brice, Jean‐Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva‐Juliane Vollstedt, Franziska Hopfner, Günter U. Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M. Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih‐Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, María Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Y. Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, K. P. Divya, Pramod Kumar Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad‐Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen‐Yang Lim, Wael Mohamed, Yi Wen Tay, Daniel Martínez-Ramírez, Mayela Rodríguez‐Violante, Paula Reyes‐Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim Anderson, Toni L. Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola O. Ojo, Jan Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Diego Véliz-Otani, Mario Cornejo‐Olivas, Maria Leila M. Doquenia, Raymond L. Rosales, Ángel Viñuela, Е. А. Яковенко, Bashayer Al Mubarak, Muhammad Umair, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Álvarez, Janet Hoenicka, Katrin Beyer, María Teresa Periñán, Pau Pástor, Sarah El-Sadig, Kajsa Brolin, Christiane Zweier, Gerd Tinkhauser, Paul Krack, Chin‐Hsien Lin, Hsiu-Chuan Wu, Pin‐Jui Kung, Ruey‐Meei Wu, Yih‐Ru Wu, Rim Amouri, Samia Ben Sassi, A. Nazl Başak, Gençer Genç, Özgür Öztop Çakmak, Sibel Ertan, Alejandro Martínez-Carrasco, Anette Schrag, Anthony H.V. Schapira, Camille Carroll, Claire Bale, Donald G. Grosset, Eleanor J. Stafford, Henry Houlden, Huw R. Morris, John Hardy, Kin Y. Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick A. Lewis, Rauan Kaiyrzhanov, Rimona S. Weil, Seth Love, Simon Stott, Simona Jasaityte, Sumit Dey, Vida Obese, Alberto J. Espay, Alyssa O’Grady, Andrew K. Sobering, Bernadette Siddiqi, Bradford Casey, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Caroline B. Pantazis, Charisse Comart, Claire Wegel, Deborah A. Hall, Dena Hernández, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E. Serrano, Honglei Chen, Ignácio F. Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Joseph Jankovic, Joshua Shulman, J Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin Levine, Lana M. Chahine, Laura Ibáñez, Laurel A. Screven, Lauren Ruffrage, Lisa M. Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew J. Koretsky, Megan J. Puckelwartz, Miguel Inca‐Martinez, Naomi Louie, Niccolò E. Mencacci, Roger L. Albin, Roy N. Alcalay, Ruth Walker, Sohini Chowdhury, Sonya B. Dumanis, Steven Lubbe, Tao Xie, Tatiana M. Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov, Cornelis Blauwendraat, Mike A. Nalls, Jia Nee Foo, Ignácio F. Mata - Nature Genetics 2023 cited by 259

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.