Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
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Published:2023-12-28
Issue:1
Volume:56
Page:27-36
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Kim Jonggeol JeffreyORCID, Vitale Dan, Otani Diego Véliz, Lian Michelle Mulan, Heilbron Karl, Aslibekyan Stella, Auton Adam, Babalola Elizabeth, Bell Robert K., Bielenberg Jessica, Bryc Katarzyna, Bullis Emily, Cannon Paul, Coker Daniella, Partida Gabriel Cuellar, Dhamija Devika, Das Sayantan, Elson Sarah L., Eriksson Nicholas, Filshtein Teresa, Fitch Alison, Fletez-Brant Kipper, Fontanillas Pierre, Freyman Will, Granka Julie M., Hernandez Alejandro, Hicks Barry, Hinds David A., Jewett Ethan M., Jiang Yunxuan, Kukar Katelyn, Kwong Alan, Lin Keng-Han, Llamas Bianca A., Lowe Maya, McCreight Jey C., McIntyre Matthew H., Micheletti Steven J., Moreno Meghan E., Nandakumar Priyanka, Nguyen Dominique T., Noblin Elizabeth S., O’Connell Jared, Petrakovitz Aaron A., Poznik G. David, Reynoso Alexandra, Schloetter Madeleine, Schumacher Morgan, Shastri Anjali J., Shelton Janie F., Shi Jingchunzi, Shringarpure Suyash, Su Qiaojuan Jane, Tat Susana A., Tchakouté Christophe Toukam, Tran Vinh, Tung Joyce Y., Wang Xin, Wang Wei, Weldon Catherine H., Wilton Peter, Wong Corinna D., Iwaki Hirotaka, Lake Julie, Solsberg Caroline WarlyORCID, Leonard Hampton, Makarious Mary B.ORCID, Tan Eng-KingORCID, Singleton Andrew B., Bandres-Ciga Sara, Noyce Alastair J., Gatto Emilia M., Kauffman Marcelo, Khachatryan Samson, Tavadyan Zaruhi, Shepherd Claire E., Hunter Julie, Kumar Kishore, Ellis Melina, Rentería Miguel E., Koks Sulev, Zimprich Alexander, Schumacher-Schuh Artur F., Rieder Carlos, Awad Paula Saffie, Tumas Vitor, Camargos Sarah, Fon Edward A., Monchi Oury, Fon Ted, Galleguillos Benjamin Pizarro, Miranda Marcelo, Bustamante Maria Leonor, Olguin Patricio, Chana Pedro, Tang Beisha, Shang Huifang, Guo Jifeng, Chan Piu, Luo Wei, Arboleda Gonzalo, Orozc Jorge, del Rio Marlene Jimenez, Hernandez Alvaro, Salama Mohamed, Kamel Walaa A., Zewde Yared Z., Brice Alexis, Corvol Jean-Christophe, Westenberger Ana, Illarionova Anastasia, Mollenhauer Brit, Klein Christine, Vollstedt Eva-Juliane, Hopfner Franziska, Höglinger Günter, Madoev Harutyun, Trinh Joanne, Junker Johanna, Lohmann Katja, Lange Lara M., Sharma Manu, Groppa Sergiu, Gasser Thomas, Fang Zih-Hua, Akpalu Albert, Xiromerisiou Georgia, Hadjigorgiou Georgios, Dagklis Ioannis, Tarnanas Ioannis, Stefanis Leonidas, Stamelou Maria, Dadiotis Efthymios, Medina Alex, Chan Germaine Hiu-Fai, Ip Nancy, Cheung Nelson Yuk-Fai, Chan Phillip, Zhou Xiaopu, Kishore Asha, Divya K. P., Pal Pramod, Kukkle Prashanth Lingappa, Rajan Roopa, Borgohain Rupam, Salari Mehri, Quattrone Andrea, Valente Enza Maria, Parnetti Lucilla, Avenali Micol, Schirinzi Tommaso, Funayama Manabu, Hattori Nobutaka, Shiraishi Tomotaka, Karimova Altynay, Kaishibayeva Gulnaz, Shambetova Cholpon, Krüger Rejko, Tan Ai Huey, Ahmad-Annuar Azlina, Norlinah Mohamed Ibrahim, Murad Nor Azian Abdul, Azmin Shahrul, Lim Shen-Yang, Mohamed Wael, Tay Yi Wen, Martinez-Ramirez Daniel, Rodriguez-Violante Mayela, Reyes-Pérez Paula, Tserensodnom Bayasgalan, Ojha Rajeev, Anderson Tim J., Pitcher Toni L., Sanyaolu Arinola, Okubadejo Njideka, Ojo Oluwadamilola, Aasly Jan O., Pihlstrøm Lasse, Tan Manuela, Ur-Rehman Shoaib, Veliz-Otani Diego, Cornejo-Olivas Mario, Doquenia Maria Leila, Rosales Raymond, Vinuela Angel, Iakovenko Elena, Mubarak Bashayer Al, Umair Muhammad, Amod Ferzana, Carr Jonathan, Bardien Soraya, Jeon Beomseok, Kim Yun Joong, Cubo Esther, Alvarez Ignacio, Hoenicka Janet, Beyer Katrin, Periñan Maria Teresa, Pastor Pau, El-Sadig Sarah, Brolin Kajsa, Zweier Christiane, Tinkhauser Gerd, Krack Paul, Lin Chin-Hsien, Wu Hsiu-Chuan, Kung Pin-Jui, Wu Ruey-Meei, Wu Yihru, Amouri Rim, Sassi Samia Ben, Başak A. Nazl, Genc Gencer, Çakmak Özgür Öztop, Ertan Sibel, Martínez-Carrasco Alejandro, Schrag Anette, Schapira Anthony, Carroll Camille, Bale Claire, Grosset Donald, Stafford Eleanor J., Houlden Henry, Morris Huw R., Hardy John, Mok Kin Ying, Rizig Mie, Wood Nicholas, Williams Nigel, Okunoye Olaitan, Lewis Patrick Alfryn, Kaiyrzhanov Rauan, Weil Rimona, Love Seth, Stott Simon, Jasaityte Simona, Dey Sumit, Obese Vida, Espay Alberto, O’Grady Alyssa, Sobering Andrew K., Siddiqi Bernadette, Casey Bradford, Fiske Brian, Jonas Cabell, Cruchaga Carlos, Pantazis Caroline B., Comart Charisse, Wegel Claire, Hall Deborah, Hernandez Dena, Shiamim Ejaz, Riley Ekemini, Faghri Faraz, Serrano Geidy E., Chen Honglei, Mata Ignacio F., Sarmiento Ignacio Juan Keller, Williamson Jared, Jankovic Joseph, Shulman Joshua, Solle Justin C., Murphy Kaileigh, Nuytemans Karen, Kieburtz Karl, Markopoulou Katerina, Marek Kenneth, Levine Kristin S., Chahine Lana M., Ibanez Laura, Screven Laurel, Ruffrage Lauren, Shulman Lisa, Marsili Luca, Kuhl Maggie, Dean Marissa, Koretsky Mathew, Puckelwartz Megan J., Inca-Martinez Miguel, Louie Naomi, Mencacci Niccolò Emanuele, Albin Roger, Alcalay Roy, Walker Ruth, Chowdhury Sohini, Dumanis Sonya, Lubbe Steven, Xie Tao, Foroud Tatiana, Beach Thomas, Sherer Todd, Song Yeajin, Nguyen Duan, Nguyen Toan, Atadzhanov Masharip, Blauwendraat CornelisORCID, Nalls Mike A.ORCID, Foo Jia Nee, Mata Ignacio, ,
Abstract
AbstractAlthough 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute on Aging U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke MOH | National Medical Research Council Innovate UK Michael J. Fox Foundation for Parkinson’s Research Aligning Science Across Parkinson’s Global Parkinson’s Genetics Program (ASAP-GP2 Ministry of Education - Singapor
Publisher
Springer Science and Business Media LLC
Reference59 articles.
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