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

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 Cuellar Partida, Devika Dhamija, Sayantan Das, Sarah L. Elson, Nicholas Eriksson, Teresa FilshteinAlison 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 Leonard, Mary B. Makarious, Eng King Tan, Andrew B. Singleton, Sara Bandres-Ciga, Alastair J. Noyce, Emilia M. Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E. Shepherd, Julie Hunter, Kishore Kumar, Melina Ellis, Miguel E. Rentería, Sulev Koks, Alexander Zimprich, Artur F. Schumacher-Schuh, Carlos Rieder, Paula Saffie Awad, Vitor Tumas, Sarah Camargos, Edward A. Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, Maria Leonor Bustamante, Patricio Olguin, Pedro Chana, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzalo Arboleda, Jorge Orozc, Marlene Jimenez del Rio, 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 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, Maria Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu Fai Chan, Nancy Ip, Nelson Yuk Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, K. P. Divya, Pramod 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 Martinez-Ramirez, Mayela Rodriguez-Violante, Paula Reyes-Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim J. Anderson, Toni L. Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola Ojo, Jan O. Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Diego Veliz-Otani, Mario Cornejo-Olivas, Maria Leila Doquenia, Raymond Rosales, Angel Vinuela, Elena Iakovenko, Bashayer Al Mubarak, Muhammad Umair, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Alvarez, Janet Hoenicka, Katrin Beyer, Maria Teresa Periñan, Pau Pastor, Sarah El-Sadig, Kajsa Brolin, Christiane Zweier, Gerd Tinkhauser, Paul Krack, Chin Hsien Lin, Hsiu Chuan Wu, Pin Jui Kung, Ruey Meei Wu, Yihru Wu, Rim Amouri, Samia Ben Sassi, A. Nazl Başak, Gencer Genc, Özgür Öztop Çakmak, Sibel Ertan, Alejandro Martínez-Carrasco, Anette Schrag, Anthony Schapira, Camille Carroll, Claire Bale, Donald Grosset, Eleanor J. Stafford, Henry Houlden, Huw R. Morris, John Hardy, Kin Ying Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick Alfryn Lewis, Rauan Kaiyrzhanov, Rimona Weil, Seth Love, Simon Stott, Simona Jasaityte, Sumit Dey, Vida Obese, Alberto 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 Hall, Dena Hernandez, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E. Serrano, Honglei Chen, Ignacio F. Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Joseph Jankovic, Joshua Shulman, Justin C. Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin S. Levine, Lana M. Chahine, Laura Ibanez, Laurel Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew Koretsky, Megan J. Puckelwartz, Miguel Inca-Martinez, Naomi Louie, Niccolò Emanuele Mencacci, Roger Albin, Roy Alcalay, Ruth Walker, Sohini Chowdhury, Sonya Dumanis, Steven Lubbe, Tao Xie, Tatiana Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov, Cornelis Blauwendraat*, Mike A. Nalls*, Jia Nee Foo*, Ignacio Mata*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalNature Genetics
Volume56
Issue number1
DOIs
Publication statusPublished - Jan 2024
Externally publishedYes

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